Ahmed H. M. Elwahy
*a and
Mohamed R. Shaaban
ab
aChemistry Department, Faculty of Science, Cairo University, Giza, Egypt. E-mail: elwahy@sci.cu.edu.eg; aelwahy@hotmail.com
bChemistry Department, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukkarramah, Saudi Arabia
First published on 17th August 2015
This review focuses, on the application of nanomaterials as heterogeneous catalysts for the synthesis of different heterocyclic systems. We pay special attention to the specific synthesis of such systems in an organized manner with respect to the type of the heterocyclic systems.
The intellectual challenge to invent concise, elegant and conceptually novel synthetic routes to heterocyclic systems has become a steadily increasing driving force both in academia and industry. Therefore, extensive efforts have been directed to develop new and efficient synthetic strategies for these compounds. Among a variety of synthetic protocols, recent researches have been focused on establishment of catalytic approaches to synthesize heterocycles from easily accessible precursors under mild reaction conditions.
In this respect, chemists have made considerable achievements during the twentieth century in heterogeneous catalysis.4 Heterogeneous catalysis have the advantage of easy removal of catalyst materials and possible use of high temperatures. Heterogeneous catalysts of metals are composed of two major components: the active metal particles and the support. Typical supports are Al2O3, SiO2, MgO, Fe2O3, TiO2, CeO2, and many others.5 The most widely used conventional method for preparing metal catalysts is the wet impregnation method.6 One area of catalysis that is developing at a rapid pace is nano-catalysis.7
Nanomaterial-based catalysts are usually heterogeneous catalysts broken up into metal nanoparticles (NPs) in order to speed up the catalytic process. Metal nanoparticles have a higher surface area so there is increased catalytic activity because more catalytic reactions can occur at the same time. Nanoparticles catalysts can also be easily separated and recycled with more retention of catalytic activity than their bulk counterparts.8 These catalysts can play two different roles in catalytic processes: they can be the site of catalysis or they can act as a support for catalytic processes.9 They are typically used under mild conditions to prevent decomposition of the nanoparticles at extreme conditions.10
Many experimental studies on nanocatalysts have focused on correlating catalytic activity with particle size. In addition, many other factors such as geometry, composition, oxidation state, and chemical/physical environment can play a role in determining NP reactivity. There are many reviews on the multiple NP synthetic modes,11 and here we will not systematically detail this aspect per se.
In continuation of our interest in reviewing the different approaches for the synthesis of heterocyclic systems,12–16 this review focuses, on the application of nanomaterials as heterogeneous catalyst for the synthesis of heterocyclic systems. A number of other reviews17,18 that have appeared, concerning this matter, did not pay special attention to the specific synthesis of such systems in an organized manner with respect to the type of the heterocyclic systems.
The fused heterocycles mentioned in this review are classified according to the type of the ring system. In order to prevent ambiguity, the fused ring systems are determined according to the following criteria:
(a) The presence or the absence of bridgehead nitrogen.
(b) Number of atoms in each ring (including carbon and hetero atoms) starting with the number of atoms in the ring taken as a prefix.
(c) The number of heteroatoms in each ring. Yields of the target molecules reported in the review are those given in the last step in the reaction except when an overall yield was given.
Cao et al. reported the regioselective synthesis of α-carbonylfurans 6a–r from a range of electron-deficient alkynes 4a–f and 3-substituted 2-yn-ols 5a–h The reaction proceeded using 10 mol% nano-Cu2O in N,N-dimethylformamide at 50 °C (Scheme 2, Table 2, Method A).20
Entry | R1 | R2 | R3 | Method | Product | Yield (%) |
---|---|---|---|---|---|---|
1 | OEt | C6H5 | H | A | 6a | 71 |
2 | OEt | C6H5 | Me | A | 6b | 67 |
3 | OEt | C6H5 | C6H5 | A | 6c | 63 |
4 | OEt | C6H5 | 3-MeC6H4 | A | 6d | 68 |
5 | OEt | C6H5 | 4-MeOC6H4 | A | 6e | 65 |
6 | OEt | C6H5 | 4-O2NC6H4 | A | 6f | 66 |
7 | OEt | C6H5 | 2-Pyridyl | A | 6g | 69 |
8 | 4-MeC6H4 | C6H5 | 2-Thienyl | A | 6h | 62 |
9 | 4-MeC6H4 | 4-MeC6H4 | H | A | 6i | 67 |
10 | 4-MeC6H4 | 4-MeC6H4 | Me | A | 6j | 73 |
11 | OEt | 4-MeC6H4 | C6H5 | A | 6k | 70 |
12 | C6H5 | Me | Me | A | 6l | 60 |
13 | C6H5 | C6H5 | H | A | 6m | 68 |
14 | C6H5 | C6H5 | C6H5 | A | 6n | 73 |
15 | C6H5 | C6H5 | Me | A | 6o | 71 |
16 | C6H5 | C6H5 | 4-MeOC6H4 | A | 6p | 71 |
17 | C6H5 | C6H5 | 4-O2NC6H4 | A | 6q | 67 |
18 | C6H5 | C6H5 | 2-Thienyl | A | 6r | 61 |
19 | OEt | C6H5 | C![]() |
B | 6s | 42 |
20 | C6H5 | C6H5 | C![]() |
B | 6t | 45 |
21 | OEt | OEt | C![]() |
B | 6u | 49 |
22 | OMe | OMe | C![]() |
B | 6v | 51 |
Furthermore, 2,4,5-trisubstituted 3-ynylfurans 6s–v were obtained in 42–51% yield by nano-Cu2O-catalyzed reaction of alkynes 4 and 5-arylpenta-2,4-diyn-1-ols 5 (Scheme 2, Table 2, entries 19–22, Method B).20
Tekale et al. have successfully developed an efficient protocol for the one-pot three-component synthesis of 3,4,5-trisubstituted furan-2(5H)-ones 10a–l from aldehydes 7a–h, amines 9a–e and dimethylacetylene dicarboxylate (DMAD) 8 using nano-crystalline ZnO as a reusable heterogeneous catalyst. The catalyst can be recycled several times with consistent catalytic activity (Scheme 3, Table 3).21
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
1 | C6H5 | C6H5 | 10a | 94 |
2 | C6H5 | 4-MeC6H4 | 10b | 95 |
3 | 4-MeOC6H4 | C6H5 | 10c | 88 |
4 | C6H5 | 4-FC6H4 | 10d | 84 |
5 | 4-ClC6H4 | C6H5 | 10e | 89 |
6 | 2-ClC6H4 | C6H5 | 10f | 87 |
7 | 3-MeOC6H4 | C6H5 | 10g | 85 |
8 | 4-MeC6H4 | C6H5 | 10h | 84 |
9 | C6H5 | 4-iPrC6H4 | 10i | 88 |
10 | C6H5 | 2-FC6H4 | 10j | 84 |
11 | 2,4-Cl2C6H3 | 2-FC6H4 | 10k | 85 |
12 | 2,4-(MeO)2C6H3 | C6H5 | 10l | 83 |
The plausible mechanism for the ZnO nanoparticle catalyzed synthesis of furan 2(5H)-ones 10a–l suggests initially the formation of enamine from amine 9 and DMAD by ZnO promotion. ZnO polarizes the carbonyl group of aldehyde 7 to form polarized adduct which reacts with the enamine followed by cyclization with the elimination of methanol molecule to afford the corresponding furan-2(5H)-ones 10a–l.
There are many Lewis and Brønsted acid sites in the sulfated metallic oxides. The superacidity of these materials is attributed to the Brønsted acid sites, created or already existing, whose acidity is increased by the presence of neighboring strong Lewis acid sites. The strength of these Lewis acid sites is due to an inductive effect exercised by sulfate on the metallic cation, which becomes more deficient in electrons,23 as seen in the Fig. 1. Thus, nano sulfated titania represents a novel type of Lewis acid catalyst.
Polshettiwar and Varma prepared nano-organocatalyst (Fig. 2) by supporting totally benign and naturally abundant glutathione on magnetic nanoparticles. The catalyst showed excellent activity for microwave-assisted synthesis of N-substituted pyrroles 12m–ab by the reaction of a variety of amines 9 with tetrahydro-2,5-dimethoxyfuran 11 (Scheme 4, Table 4, Method B). The rates were essentially the same for both the aliphatic or aromatic nature of the amines, showing the high activity of the catalyst.24
Ma et al. reported a facile approach to prepare magnetic nanoparticle-supported antimony catalyst (Fe2O3@SiO2–Sb–IL, Fig. 3). This catalyst exhibited excellent catalytic efficiency in Clauson–Kaas reaction of amines 9 to 2,5-dimethoxytetrahydrofuran 11 in aqueous medium to afford the corresponding N-substituted pyrroles 12b, 12f, 12k, 12l, 12u and 12ac–bm (Scheme 4, Table 4, Method C).25
N-Substituted pyrroles 14a–g have also been prepared from one-pot Paal–Knorr condensation of 2,5-diketone 13 and the appropriate aromatic amine 9 using nano-crystalline sulfated zirconia (SZ) as the catalyst in ethanol at moderate temperature (Scheme 5, Table 5).26
Entry | R | Product | Yield (%) |
---|---|---|---|
1 | C6H5 | 14a | 94 |
2 | 4-ClC6H4 | 14b | 90 |
3 | 4-BrC6H4 | 14c | 85 |
4 | 4-O2NC6H4 | 14d | 90 |
5 | C6H5CH2NH2 | 14e | 81 |
6 | 4-MeC6H4 | 14f | 90 |
7 | 4-MeOC6H4 | 14g | 86 |
Li et al. reported one-pot three-component synthesis of multisubstituted pyrroles 17a–av by the reaction of amines 9, nitroolefins 16 and 1,3-dicarbonyl compounds 15 catalyzed by novel magnetic nano-CoFe2O4 supported Sb ([CoFe2O4@SiO2–DABCO–Sb], Fig. 4), (Scheme 6, Table 6). The magnetic heterogeneous catalyst could be easily recovered using an external magnet and reused many times without significant loss of catalytic activity.27
Entry | R1 | R2 | R3 | R4 | Ar | Product | Yield (%) |
---|---|---|---|---|---|---|---|
1 | C6H5 | Me | Me | H | C6H5 | 17a | 93 |
2 | C6H5 | Me | Me | Me | C6H5 | 17b | 80 |
3 | C6H5 | Me | Me | Me | 4-MeC6H4 | 17c | 87 |
4 | C6H5 | Me | Me | Me | 4-FC6H4 | 17d | 86 |
5 | C6H5 | Me | Me | Me | 2-ClC6H4 | 17e | 75 |
6 | C6H5 | Me | Me | Me | 3-ClC6H4 | 17f | 78 |
7 | C6H5 | Me | Me | Me | 4-ClC6H4 | 17g | 85 |
8 | C6H5 | Me | Me | Me | 4-O2NC6H4 | 17h | 75 |
9 | C6H5 | Me | Me | Me | 2-Furyl | 17i | 88 |
10 | C6H5 | Me | Me | Me | 2-Thienyl | 17j | 82 |
11 | C6H5 | Me | Me | Me | 2-Naphthyl | 17k | 47 |
12 | C6H5 | Me | Me | Et | C6H5 | 17l | 80 |
13 | C6H5 | Me | Me | Et | 4-MeC6H4 | 17m | 80 |
14 | C6H5 | Me | Me | Et | 2-Furyl | 17n | 76 |
15 | C6H5 | Me | Me | Et | 2-Thienyl | 17o | 78 |
16 | 4-tBuC6H4 | Me | Me | H | C6H5 | 17p | 92 |
17 | 2-Naphthyl | Me | Me | H | C6H5 | 17q | 75 |
18 | 4-Fluorenyl | Me | Me | H | C6H5 | 17r | 80 |
19 | 4-MeC6H4 | Me | Me | Me | C6H5 | 17s | 82 |
20 | 4-MeOC6H4 | Me | Me | Me | C6H5 | 17t | 88 |
21 | 4-FC6H4 | Me | Me | Me | C6H5 | 17u | 82 |
22 | 4-CIC6H4 | Me | Me | Me | C6H5 | 17v | 75 |
23 | 2-BrC6H4 | Me | Me | Me | C6H5 | 17w | 70 |
24 | 3-BrC6H4 | Me | Me | Me | C6H5 | 17x | 72 |
25 | 4-BrC6H4 | Me | Me | Me | C6H5 | 17y | 77 |
26 | 4-F3CC6H4 | Me | Me | Me | C6H5 | 17z | 51 |
27 | 4-F3COC6H4 | Me | Me | Me | C6H5 | 17aa | 85 |
28 | 2-Furyl-CH2 | Me | Me | Me | C6H5 | 17ab | 90 |
29 | 2-Fluorenyl | Me | Me | Me | C6H5 | 17ac | 73 |
30 | Allyl | Me | Me | Me | C6H5 | 17ad | 91 |
31 | Bn | Me | Me | Me | C6H5 | 17ae | 90 |
32 | C6H5CH2CH2 | Me | Me | Me | C6H5 | 17af | 92 |
33 | C6H5CH(CH3)– | Me | Me | Me | C6H5 | 17ag | 87 |
34 | cPr | Me | Me | Me | C6H5 | 17ah | 89 |
35 | cPn | Me | Me | Me | C6H5 | 17ai | 72 |
36 | nPr | Me | Me | Me | C6H5 | 17aj | 88 |
37 | nBu | Me | Me | Me | C6H5 | 17ak | 86 |
38 | C6H5 | Me | OMe | Me | C6H5 | 17al | 82 |
39 | C6H5 | Me | OEt | Me | C6H5 | 17am | 85 |
40 | C6H5 | Me | O(CH2)2OMe | Me | C6H5 | 17an | 80 |
41 | C6H5 | 41 | O-Allyl | Me | C6H5 | 17ao | 78 |
42 | C6H5 | Et | OMe | Me | C6H5 | 17ap | 76 |
43 | C6H5 | Me | OCMe3 | Me | C6H5 | 17aq | 83 |
44 | C6H5 | Me | OCH2CH(CH3)2 | Me | C6H5 | 17ar | 81 |
45 | 2-Furyl-CH2 | Me | Me | Et | C6H5 | 17as | 89 |
46 | Bn | Me | Me | Et | C6H5 | 17at | 86 |
47 | cPr | Me | Me | Et | C6H5 | 17au | 82 |
48 | nPr | Me | Me | Et | C6H5 | 17av | 83 |
Sabbaghan and Ghalaei et al. reported a simple procedure for synthesis of polysubstituted pyrroles 20a–m by the three-component reaction of amines 9, phenacyl bromide 18 and dialkyl acetylenedicarboxylates 19 under solvent free conditions using nano structures of ZnO as catalyst (Scheme 7, Table 7).28
Entry | R1 | R2 | R3 | Product | Yield (%) |
---|---|---|---|---|---|
1 | Et | C6H5 | COOMe | 20a | 90 |
2 | Et | C6H5 | COOEt | 20b | 88 |
3 | Bn | C6H5 | COOMe | 20c | 90 |
4 | Bn | C6H5 | COOEt | 20d | 94 |
5 | 4-ClC6H2–CH2– | C6H5 | COOEt | 20e | 92 |
6 | 4-MeC6H2–CH2– | C6H5 | COOEt | 20f | 86 |
7 | nHexyl | C6H5 | COOMe | 20g | 92 |
8 | nHexyl | C6H5 | COOEt | 20h | 86 |
9 | Et | 4-MeOC6H4 | COOEt | 20i | 75 |
10 | Et | 4-ClC6H4 | COOMe | 20j | 78 |
11 | C6H5 | C6H5 | COOEt | 20k | 0 |
12 | 4-MeOC6H5 | C6H5 | COOEt | 20l | 0 |
13 | nHexyl | COOEt | COOMe | 20m | 0 |
ZnO nano particles catalyze the reaction through its Lewis acid sites (Zn2+) and Lewis basic sites (O2−).29,30 In this reaction, the Zn2+ sites are interacting with carbonyl groups in acetylenic compound and phenacyl bromide and Lewis basic sites [O2− ] taking up a proton from the generated enamine to give the pyrrole structure.
A magnetic nanoparticle CoFe2O4 supported molybdenum catalyst ([CoFe2O4@SiO2-PrNH2-Mo(acac)2]), (Fig. 5), was prepared and found to be a highly active and efficient catalyst for a one-pot synthesis of polysubstituted pyrroles 22a–aq via a four-component reaction of aldehydes 7, amines 9, 1,3-dicarbonyl compounds 15 and nitromethane 21 (Scheme 8, Table 8). The catalyst could be easily recovered by simple magnetic decantation and reused five times without significant loss of activity.31
![]() | ||
Fig. 5 Structure of a magnetic nanoparticle CoFe2O4 supported molybdenum catalyst ([CoFe2O4@SiO2-PrNH2-Mo(acac)2]). |
Entry | R1 | R2 | R3 | R4 | Product | Yield (%) |
---|---|---|---|---|---|---|
1 | C6H5 | Me | Me | C6H5 | 22a | 90 |
2 | 4-MeOC6H4 | Me | Me | C6H5 | 22b | 86 |
3 | 4-MeC6H4 | Me | Me | C6H5 | 22c | 92 |
4 | 4-FC6H4 | Me | Me | C6H5 | 22d | 90 |
5 | 4-ClC6H4 | Me | Me | C6H5 | 22e | 80 |
6 | 4-BrC6H4 | Me | Me | C6H5 | 22f | 82 |
7 | 4-O2NC6H4 | Me | Me | C6H5 | 22g | 50 |
8 | 4-F3COC6H4 | Me | Me | C6H5 | 22h | 80 |
9 | 1-Naphthyl | Me | Me | C6H5 | 22i | 48 |
10 | 2-Fluorenyl | Me | Me | C6H5 | 22j | 83 |
11 | Allyl | Me | Me | C6H5 | 22k | 88 |
12 | Bn | Me | Me | C6H5 | 22l | 90 |
13 | 4-MeC6H4–CH2– | Me | Me | C6H5 | 22m | 91 |
14 | 4-FC6H4–CH2– | Me | Me | C6H5 | 22n | 87 |
15 | C6H4–CH2–CH2– | Me | Me | C6H5 | 22o | 91 |
16 | 4-HOC6H4–CH2–CH2– | Me | Me | C6H5 | 22p | 90 |
17 | cPr | Me | Me | C6H5 | 22q | 90 |
18 | cPn | Me | Me | C6H5 | 22r | 86 |
19 | nPr | Me | Me | 4-FC6H4 | 22s | 90 |
20 | C6H5 | Me | Me | 4-(Me2)CHOC6H4 | 22t | 81 |
21 | C6H5 | Me | Me | 4-FC6H4 | 22u | 87 |
22 | C6H5 | Me | Me | 4-ClC6H4 | 22v | 86 |
23 | C6H5 | Me | Me | 4-BrC6H4 | 22w | 85 |
24 | C6H5 | Me | Me | 4-O2NC6H4 | 22x | 83 |
25 | C6H5 | Me | Me | 4-F3CC6H4 | 22y | 85 |
26 | C6H5 | Me | Me | 2-Furyl | 22z | 60 |
27 | C6H5 | Me | Me | 2-Thienyl | 22aa | 71 |
28 | C6H5 | Me | Me | 1-Naphthyl | 22ab | 80 |
29 | 4-MeC6H4–CH2– | Me | Me | 2-Thienyl | 22ac | 80 |
30 | 4-FC6H4 | Me | Me | 2-Thienyl | 22ad | 75 |
31 | 4-FC6H4 | Me | Me | 2-(5-Methylthienyl) | 22ae | 78 |
32 | 4-ClC6H4 | Me | Me | 2-(5-Methylthienyl) | 22af | 70 |
33 | 2-Fluorenyl | Me | Me | 2-(5-Methylthienyl) | 22ag | 80 |
34 | Bn | Me | Me | 2-Thienyl | 22ah | 80 |
35 | C6H4–CH2–CH2– | Me | Me | 4-MeC6H4 | 22ai | 88 |
36 | C6H4–CH2–CH2– | Me | Me | 4-FC6H4 | 22aj | 89 |
37 | C6H4–CH2–CH2– | Me | Me | 3-F3CC6H4 | 22ak | 85 |
38 | cPr | Me | Me | 4-tBuC6H4 | 22al | 88 |
39 | C6H5 | Me | OMe | C6H5 | 22am | 80 |
40 | C6H5 | Me | OEt | C6H5 | 22an | 82 |
41 | C6H5 | Me | O(CH2)2OMe | C6H5 | 22ao | 80 |
42 | C6H5 | Me | O-Allyl | C6H5 | 22ap | 78 |
43 | C6H5 | Et | OMe | C6H5 | 22aq | 80 |
Entry | R1 | R2 | R3 | R4 | Product | Method | Yield (%) |
---|---|---|---|---|---|---|---|
1 | 2,4-(O2N)2–C6H3 | Me | H | Me | 24a | A | 85 |
2 | 2,4-(O2N)2–C6H3 | C6H5 | H | Me | 24b | A | 92 |
3 | 2,4-(O2N)2–C6H3 | C6H5 | H | C6H5 | 24c | A | 92 |
4 | 2,4-(O2N)2–C6H3 | Me | Cl | Me | 24d | A | 89 |
5 | C6H5 | C6H5 | H | C6H5 | 24e | A | 93 |
6 | C6H5 | Me | Cl | Me | 24f | A | 93 |
7 | H | C6H5 | H | Me | 24g | A | 87 |
8 | 4-BrC6H4 | Me | Cl | Me | 24h | A | 94 |
9 | 4-BrC6H4 | C6H5 | H | C6H5 | 24i | A | 90 |
10 | 4-BrC6H4 | C6H5 | H | Me | 24j | A | 92 |
11 | 4-MeC6H4 | C6H5 | H | C6H5 | 24k | A | 87 |
12 | 4-MeC6H4 | C6H5 | H | Me | 24l | A | 89 |
13 | 4-MeOC6H4 | C6H5 | H | C6H5 | 24m | A | 74 |
14 | 4-MeOC6H4 | C6H5 | H | Me | 24n | A | 88 |
15 | 4-MeC6H4SO2 | Me | H | Me | 24o | A | 83 |
16 | 4-MeC6H4SO2 | C6H5 | H | C6H5 | 24p | A | 83 |
17 | 4-MeC6H4SO2 | C6H5 | H | Me | 24q | A | 84 |
18 | C6H5 | Me | H | Me | 24r | B | 96 |
19 | C6H5 | Me | Cl | Me | 24s | B | 80 |
20 | C6H5 | Me | Et | Me | 24t | B | 84 |
21 | 4-ClC6H4 | Me | H | Me | 24u | B | 82 |
22 | 4-ClC6H4 | Me | Cl | Me | 24v | B | 78 |
23 | 4-ClC6H4 | Me | Et | Me | 24w | B | 84 |
24 | C6H5CO | Me | H | Me | 24x | B | 88 |
25 | 2-Furoyl | Me | H | Me | 24y | B | 84 |
Various hydrazines and hydrazides reacted also efficiently with 1,3-diketones in the presence of supported glutathione on magnetic nanoparticles (Fig. 2) under microwave irradiation to give the pyrazoles 24r–y in good yields (Scheme 9, Table 9, Method B).24
Entry | R1 | R2 | Product | Method | Yield (%) |
---|---|---|---|---|---|
a In Method B MW yields% were indicated between parentheses. | |||||
1 | C6H5 | H | 26a | A | 95 |
2 | 4-MeC6H4 | H | 26b | A | 83 |
3 | 4-O2NC6H4 | H | 26c | A | 96 |
4 | 4-ClC6H4 | H | 26d | A | 95 |
5 | 2-MeOC6H4 | H | 26e | A | 80 |
6 | 4-MeOC6H4 | H | 26f | A | 85 |
7 | 2-ClC6H4 | H | 26g | A | 89 |
8 | 2,4-Cl2C6H4 | H | 26h | A | 91 |
9 | 4-BrC6H4 | H | 26i | A | 92 |
10 | 2-O2NC6H4 | H | 26j | A | 87 |
11 | 3-O2NC6H4 | H | 26k | A | 93 |
12 | 2-BrC6H4 | H | 26l | A | 90 |
13 | C6H5 | H | 26a | B | 85(96) |
14 | 4-MeC6H4 | H | 26b | B | 87(99) |
15 | 3-MeC6H4 | H | 26m | B | 76(95) |
16 | 4-MeC6H4 | H | 26b | B | 82(98) |
17 | 4-ClC6H4 | H | 26d | B | 78(95) |
18 | 3-ClC6H4 | H | 26n | B | 83(95) |
19 | 4-BrC6H4 | H | 26i | B | 88(93) |
20 | 3-BrC6H4 | H | 26o | B | 78(95) |
21 | 2-Naphthyl | H | 26p | B | 77(94) |
22 | 2,4-Cl2C6H3 | H | 26q | B | 79(94) |
23 | 2-Thienyl | H | 26r | B | 75(95) |
24 | 3-O2NC6H4 | H | 26k | B | 85(93) |
25 | 4-Me2NC6H4 | H | 26s | B | 77(96) |
26 | 2-HOC6H4 | H | 26t | B | 85(93) |
27 | 3-HOC6H4 | H | 26u | B | 90(93) |
28 | C6H5 | H | 26a | C | 90 |
29 | 4-Me2NC6H4 | H | 26s | C | 91 |
30 | 4-MeOC6H4 | H | 26f | C | 92 |
31 | 2-MeOC6H4 | H | 26e | C | 89 |
32 | 2-ClC6H4 | H | 26g | C | 88 |
33 | 4-ClC6H4 | H | 26d | C | 89 |
34 | 2,4-Cl2C6H3 | H | 26q | C | 84 |
35 | 4-BrC6H4 | H | 26i | C | 89 |
36 | 2-O2NC6H4 | H | 26j | C | 85 |
37 | 3-O2NC6H4 | H | 26k | C | 87 |
38 | 4-O2NC6H4 | H | 26c | C | 89 |
39 | 4-MeC6H4 | H | 26b | C | — |
40 | C6H5 | H | 26a | D | 95 |
41 | 4-MeOC6H4 | H | 26f | D | 90 |
42 | 3-MeOC6H4 | H | 26v | D | 92 |
43 | 4-ClC6H4 | H | 26d | D | 96 |
44 | 3-MeOC6H4 | H | 26v | D | 98 |
45 | 2-Naphthyl | H | 26p | D | 98 |
46 | 3-MeOC6H4 | H | 26v | D | 98 |
47 | C6H5 | OMe | 26w | D | 95 |
48 | 4-MeOC6H4 | OMe | 26x | D | 90 |
49 | 2-Naphthyl | OMe | 26y | D | 95 |
50 | 3-MeOC6H4 | F | 26vz | D | 98 |
51 | 2-Naphthyl | F | 26aa | D | 98 |
52 | C6H5 | H | 26a | E | 87 |
53 | 4-ClC6H4 | H | 26d | E | 92 |
54 | 4-BrC6H4 | H | 26i | E | 81 |
55 | 4-O2NC6H4 | H | 26c | E | 80 |
56 | 4-HOC6H4 | H | 26ab | E | 82 |
57 | 4-MeC6H4 | H | 26b | E | 93 |
58 | 4-MeOC6H4 | H | 26f | E | 85 |
59 | C6H5 | H | 26a | F | 100 |
60 | 4-ClC6H4 | H | 26d | F | 99 |
61 | 4-MeOC6H4 | H | 26f | F | 98 |
62 | 4-HOC6H4 | H | 26ac | F | 80 |
63 | 4-Me2NC6H4 | H | 26s | F | 93 |
64 | 3-O2NC6H4 | H | 26k | F | 87 |
65 | 2-HOC6H4 | H | 26t | F | 80 |
66 | C6H5 | H | 26a | G | 98 |
67 | 3-O2NC6H4 | H | 26k | G | 79 |
68 | 4-MeC6H4 | H | 26b | G | 88 |
69 | 2-ClC6H4 | H | 26g | G | 95 |
70 | 4-ClC6H4 | H | 26d | G | 86 |
71 | 3,4-Cl2C6H3 | H | 26ad | G | 83 |
72 | 4-MeOC6H4 | H | 26f | G | 85 |
73 | 2-MeOC6H4 | H | 26e | G | 78 |
Safari and Zarnegar also synthesized trisubstituted imidazoles 26 in high yield in the presence of sulphamic acid functionalized magnetic Fe3O4 nanoparticles (SA–MNPs, Fig. 6) as a novel solid acid catalyst. The reaction proceeds via a three component reaction of benzil 25, aromatic aldehyde 7 and ammonium acetate under solvent-free classical heating conditions or using microwave irradiation (Scheme 10, Table 10, Method B). The heterogeneous catalyst could be recovered easily and reused many times without significant loss of catalytic activity.34
Nano-TiCl4·SiO2 has been found to be an extremely efficient catalyst for the preparation of 2,4,5-trisubstituted imidazoles 26 via similar three-component reactions (Scheme 10, Table 10, Method C). Nano-TiCl4·SiO2 as a solid Lewis acid has been synthesized by reaction of nano-SiO2 and TiCl4.35
Zarnegar and Safari prepared chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS, Fig. 7) through in situ co-precipitation of Fe2+ and Fe3+ ions via NH4OH in an aqueous solution of chitosan and investigated their catalytic activity in the synthesis of 2,4,5-trisubstituted imidazoles 26 by a similar one-pot reaction (Scheme 10, Table 10, Method D).36
Teimouri and Chermahini reported a synthesis of 2,4,5-trisubstituted imidazoles 26 by a similar three components cyclocondensation reaction using nano-crystalline sulfated zirconia (SZ) as catalyst in ethanol at moderate temperature (Scheme 10, Table 10, Method E). It can be seen that electron donating and electron withdrawing groups does not show any difference on the reaction yields.37
Sulfonic acid functionalized SBA-15 nanoporous material (SBA-Pr–SO3H) with a pore size of 6 nm was found to be a green and effective solid acid catalyst in the one-pot synthesis of 2,4,5-trisubstituted imidazoles 26 under solvent-free conditions (Scheme 10, Table 10, Method F).38
Keivanloo et al. used boehmite nanoparticles (AlOOH NPs) as a highly active and green catalyst for the synthesis of highly substituted imidazoles 26 under solvent-free conditions (Scheme 10, Table 10, Method G).39
Teimouri and Chermahinib reported a versatile and efficient synthesis of 1,2,4,5-tetrasubstituted imidazoles 27 in high yields by four component cyclocondensation of benzyl 25, aniline 9, ammonium acetate and various aromatic aldehydes 7 using nano-crystalline sulfated zirconia (SZ) as a catalyst in ethanol at moderate temperature (Scheme 11, Table 11, Method A).37
Entry | R1 | R2 | R3 | Method | Product | Yield (%) |
---|---|---|---|---|---|---|
1 | C6H5 | C6H5 | H | A | 27a | 87 |
2 | 4-ClC6H4 | C6H5 | H | A | 27b | 92 |
3 | 4-BrC6H4 | C6H5 | H | A | 27c | 85 |
4 | 4-O2NC6H4 | C6H5 | H | A | 27d | 76 |
5 | 4-HOC6H4 | C6H5 | H | A | 27e | 85 |
6 | 4-MeC6H4 | C6H5 | H | A | 27f | 87 |
7 | 4-MeOC6H4 | C6H5 | H | A | 27g | 80 |
8 | 4-ClC6H4 | C6H5 | H | B | 27b | 100 |
9 | 4-ClC6H4 | Bn | H | B | 27h | 100 |
10 | 4-MeOC6H4 | C6H5 | H | B | 27g | 97 |
11 | 4-MeC6H4 | C6H5 | H | B | 27f | 99 |
12 | 4-MeC6H4 | Bn | H | B | 27i | 95 |
13 | 4-Me2NC6H4 | Bn | H | B | 27j | 99 |
14 | 3-O2NC6H4 | C6H5 | H | B | 27k | 95 |
15 | 3-MeOC6H4 | Bn | H | B | 27l | 84 |
16 | C6H5 | C6H5 | H | C | 27a | 94 |
17 | C6H5 | Bn | H | C | 27m | 92 |
18 | 4-O2NC6H4 | 4-MeC6H4 | H | C | 27n | 80 |
19 | 4-ClC6H4 | C6H5 | H | C | 27b | 85 |
20 | 4-MeC6H4 | Bn | H | C | 27i | 75 |
21 | 4-MeC6H4 | C6H5 | H | C | 27f | 91 |
22 | 4-ClC6H4 | 4-O2NC6H4 | H | C | 27o | 79 |
23 | 4-O2NC6H4 | Bn | H | C | 27p | 81 |
24 | 4-MeC6H4 | Bn | H | C | 27i | 87 |
25 | 4-ClC6H4 | Bn | H | C | 27h | 82 |
26 | 4-MeOC6H4 | C6H5 | H | C | 27g | 92 |
27 | 4-MeOC6H4 | Bn | H | C | 27q | 93 |
28 | C6H5 | Me | H | C | 27r | 80 |
29 | C6H5 | C6H5 | H | D | 27a | 82 |
30 | C6H5 | Bn | H | D | 27m | 84 |
31 | C6H5 | cHexyl | H | D | 27s | 64 |
32 | C6H5 | Et | H | D | 27t | 70 |
33 | 4-ClC6H4 | C6H5 | H | D | 27b | 81 |
34 | 4-ClC6H4 | Bn | H | D | 27h | 79 |
35 | 2-ClC6H4 | Bn | H | D | 27u | 83 |
36 | 4-HOC6H4 | Bn | H | D | 27v | 68 |
37 | 4-MeC6H4 | C6H5 | H | D | 27f | 73 |
38 | 4-MeC6H4 | Bn | H | D | 27i | 91 |
39 | 4-MeC6H4 | cHexyl | H | D | 27w | 75 |
40 | 3-MeOC6H4 | Bn | H | D | 27l | 91 |
41 | 2-O2NC6H4 | Bn | H | D | 27x | 86 |
42 | iPr | Bn | H | D | 27y | 60 |
43 | C6H5 | C6H5 | H | E | 27a | 94 |
44 | C6H5 | Bn | H | E | 27m | 96 |
45 | 4-MeC6H4 | C6H5 | H | E | 27f | 86 |
46 | 4-ClC6H4 | C6H5 | H | E | 27b | 92 |
47 | C6H5 | 3-ClC6H4 | H | E | 27z | 93 |
48 | 4-O2NC6H4 | C6H5 | H | E | 27d | 78 |
49 | C6H5 | cHexyl | H | E | 27s | 89 |
50 | C6H5 | 4-O2NC6H4 | H | E | 27aa | 80 |
51 | C6H5 | nPr | H | E | 27ab | 88 |
52 | C6H5 | MeOCH2CH2– | H | E | 27ac | 90 |
53 | C6H5 | iPr | H | E | 27ad | 85 |
54 | C6H5 | nBu | H | E | 27ae | 86 |
55 | C6H5 | 2-THF–CH2– | H | E | 27af | 78 |
56 | 4-O2NC6H4 | 3,4-Me2C6H3 | H | F | 27ag | 96 |
57 | 3-O2NC6H4 | 3,4-Me2C6H3 | H | F | 27ah | 96 |
58 | 4-NCC6H4 | 3,4-Me2C6H3 | H | F | 27ai | 94 |
59 | 4-MeOC6H4 | 4-MeC6H4 | H | F | 27aj | 94 |
60 | 3-O2NC6H4 | 3-MeC6H4 | H | F | 27ak | 95 |
61 | 4-BrC6H4 | 4-MeOC6H4 | H | F | 27al | 94 |
62 | 3-O2NC6H4 | 3-MeOC6H4 | H | F | 27am | 91 |
63 | 4-NCC6H4 | 4-MeC6H4 | H | F | 27an | 92 |
64 | 4-MeOC6H4 | 3,4-Me2C6H3 | H | F | 27ao | 88 |
65 | 4-O2NC6H4 | Bn | Cl | F | 27ap | 96 |
66 | 4-O2NC6H4 | 3,4-Me2C6H3 | Cl | F | 27aq | 97 |
67 | 3-O2NC6H4 | 3,4-Me2C6H3 | Cl | F | 27ar | 97 |
68 | 4-O2NC6H4 | 3,4-Me2C6H3 | Me | F | 27as | 85 |
69 | nPr | cHexyl | H | F | 27at | 78 |
70 | 4-BrC6H4 | cHexyl | H | F | 27au | 95 |
71 | 4-MeOC6H4 | cHexyl | H | F | 27av | 89 |
72 | 4-Pyridyl | 3,4-Me2C6H3 | H | F | 27aw | 83 |
73 | 3-O2NC6H4 | 3-O2NC6H4 | H | F | 27ax | 91 |
74 | 4-ClC6H4 | 3,4-Me2C6H3 | H | F | 27ay | 97 |
Ziarani et al. used sulfonic acid functionalized SBA-15 nanoporous material (SBA-Pr–SO3H) with a pore size of 6 nm as an effective catalyst in the synthesis of a variety of tetrasubstituted imidazoles 27 (Scheme 11, Table 11, Method B).38
Montazeri et al. reported also a four-component synthesis of 1,2,4,5-tetrasubstituted imidazoles 27 using nano Fe3O4 as magnetically recyclable catalyst under solvent free conditions (Scheme 11, Table 11, Method C).40
Mirjalili et al. applied nano-TiCl4 ·SiO2 (Fig. 8) as an efficient catalyst for synthesis of 1,2,4,5-triphenylimidazoles 27 with good to excellent yields via a similar four-component reaction (Scheme 11, Table 11, Method D).41
Keivanloo et al. reported the synthesis of 1,2,4,5-tetrasubstituted imidazoles 27 catalyzed by oboehmite nanoparticles (AlOOH NPs) under solvent-free conditions (Scheme 11, Table 11, Method E). The results show that the reactions are equally facile with both electron donating and electron-withdrawing substituents present on both the aromatic aldehydes 7 and aromatic amines 9, resulting in good-to high yields of the corresponding imidazoles 27. Aliphatic amines also reacted efficiently, affording the desired products in 78–90% yield.39
Ray et al. prepared a porous silica nano particle (PSNP-CA, Fig. 9), by post synthesis grafting of COOH functionalized organosilane on porous silica nano particle by using surface hydroxyl groups as anchor point. This catalyst was found to promote the chemoselective synthesis of 1,2,4,5-tetrasubstituted imidazole 27 in water during a similar four multi-component reaction (Scheme 11, Table 11, Method F).42
Mitra et al. have explored the use of nano In2O3 as an effective and versatile catalyst for the synthesis of 4,5-unsymmetrically substituted 1H-imidazoles 26ae-ap in good yields. The reaction was performed by the reaction of varying amidines 28 with a wide range of structurally diverse nitroolefins 29 (Scheme 12, Table 12). As it is evident from Table 12, this procedure is uniformly effective for nitroolefins with different substituents on the benzene ring as well as for aliphatic nitroolefin.43 Based on previous results, the indium(III) catalyst promotes Michael addition of amidine–nitroolefin by activating the double bond.44
Entry | R1 | R2 | R3 | Product | Yield (%) |
---|---|---|---|---|---|
1 | C6H5 | Me | C6H5 | 26ae | 88 |
2 | C6H5 | Me | 4-MeOC6H4 | 26af | 80 |
3 | C6H5 | Me | 4-ClC6H4 | 26ag | 70 |
4 | C6H5 | Me | 4-MeC6H4 | 26ah | 80 |
5 | C6H5 | Me | 4-BrC6H4 | 26ai | 72 |
6 | C6H5 | Me | iPr | 26aj | 65 |
7 | C6H5 | Me | 3,4-CH2O2C6H3 | 26ak | 81 |
8 | C6H5 | Me | 2-Furyl | 26al | 79 |
9 | C6H5 | Et | C6H5 | 26am | 70 |
10 | 3-O2NC6H4 | Me | C6H5 | 26an | 75 |
11 | 3-O2NC6H4 | Me | 4-MeOC6H4 | 26ao | 82 |
12 | Me | Me | C6H5 | 26ap | 55 |
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
1 | C6H5 | C6H5 | 31a | 94 |
2 | C6H5 | 4-MeC6H4 | 31b | 90 |
3 | C6H5 | 4-ClC6H4 | 31c | 90 |
4 | C6H5 | 4-O2NC6H4 | 31d | 86 |
5 | 4-MeC6H4 | 4-MeC6H4 | 31e | 93 |
6 | 4-MeC6H4 | C6H5 | 31f | 88 |
7 | 4-ClC6H4 | C6H5 | 31g | 95 |
8 | 4-O2NC6H4 | C6H5 | 31h | 92 |
9 | 4-O2NC6H4 | 4-MeC6H4 | 31i | 90 |
10 | 3-O2NC6H4 | C6H5 | 31j | 89 |
Entry | R1 | Product | MW yield (%) | Δ yield (%) |
---|---|---|---|---|
1 | 4-ClC6H4 | 33a | 96 | 91 |
2 | C6H5 | 33b | 91 | 88 |
3 | 4-MeOC6H4 | 33c | 95 | 91 |
4 | C6H5 | 33d | 91 | 87 |
5 | 3,4-(HO)2C6H3 | 33e | 95 | 91 |
6 | 2,6-Cl2C6H4 | 33f | 91 | 88 |
7 | 2,4-(MeO)2C6H3 | 33g | 94 | 90 |
8 | 4-HOC6H4 | 33h | 94 | 89 |
9 | 2-Pyrrolyl | 33i | 95 | 87 |
10 | 2-Thienyl | 33j | 94 | 88 |
11 | 4-FC6H4 | 33k | 94 | 90 |
12 | 2,4-Cl2C6H4 | 33l | 92 | 89 |
13 | 2-Pyridyl | 33m | 95 | 87 |
Entry | Ar | R | Product | Yield (%) |
---|---|---|---|---|
1 | C6H5 | C6H5 | 36a | 94 |
2 | 2-FC6H5 | C6H5 | 36b | 94 |
3 | 3-O2NC6H4 | C6H5 | 36c | 95 |
4 | 3,5-F2C6H4 | C6H5 | 36d | 96 |
5 | 4-MeC6H4 | C6H5 | 36e | 94 |
6 | 4-MeOC6H4 | C6H5 | 36f | 97 |
7 | 4-ClC6H5 | C6H5 | 36g | 96 |
8 | 4-HOC6H4 | C6H5 | 36h | 94 |
9 | 2-Naphthyl | C6H5 | 36i | 94 |
10 | C6H5 | 4-MeC6H4 | 36j | 95 |
11 | C6H5 | 3-NH2C6H4 | 36k | 95 |
12 | C6H5 | nPr | 36l | 93 |
13 | C6H5 | nBu | 36m | 89 |
14 | C6H5 | nPn | 36n | 91 |
15 | C6H5 | CH2OH | 36o | 92 |
16 | C6H5 | CH3(CH2)3–CH(OH–) | 36p | 90 |
17 | C6H5 | COOH | 36q | 94 |
The authors proposed mechanism for Cu2–β-CD catalyzed in situ azidation of arylboronic acids 34 for the synthesis of 1,2,3-triazoles 36a–q. The reaction is initiated by transmetallation of the aryl group from Boron to copper via the attack of the hydroxide ligand to the oxophilic boron center. The resulting arylcopper intermediate undergoes subsequent reductive azidation to the arylazide compound (Fig. 11). According to literature reports for the Cu-catalyzed azide–alkyne 1,3-dipolar cycloaddition,48 the 1,2,3-triazole formation proceeds through attack of the hydroxido ligand of Cu2–β-CD complex to the terminal hydrogen of acetylene to give copper acetylide. Continuing, coordination of the arylazide to the copper center of the acetylide initiates an azide–alkyne 1,3-dipolar cycloaddition.
![]() | ||
Fig. 11 Mechanism for in situ azidation of arylboronic acids for the synthesis of 1,2,3-triazoles catalyzed by Cu2–β-CD. |
Kamal and Swapna developed a new Fe2O3 nanoparticle catalyzed three-component reaction for the construction of 2,4,5-trisubstituted-1,2,3-triazoles 39a–x from chalcones 37, sodium azide and aryl halides 38. This tandem three-component reaction involves an oxidative 1,3-dipolar cycloaddition of the chalcone and azide and subsequent regioselective N-2-arylation (Scheme 16, Table 16). Control experiments suggest that atmospheric oxygen acts as the sacrificial oxidant in the reaction. The reaction has good substrate scope and furnishes the products in very good yields. Importantly, the catalyst is easily recoverable and may be reused without any significant loss in catalytic activity.49
Entry | R1 | R2 | R3 | X | Product | Yield (%) |
---|---|---|---|---|---|---|
1 | 2-FC6H4 | 2-FC6H4 | 2-O2NC6H4 | F | 39a | 92 |
2 | 4-FC6H4 | 3-CF3C6H4 | 2-O2NC6H4 | F | 39b | 90 |
3 | 4-O2NC6H4 | C6H5 | 2-O2NC6H4 | F | 39c | 89 |
4 | 3-F-4-ClC6H3 | 4-FC6H4 | 2-O2NC6H4 | F | 39d | 80 |
5 | 4-CF3C6H4 | 4-FC6H4 | 2-O2NC6H4 | F | 39e | 80 |
6 | 4-MeC6H4 | C6H5 | 2-O2NC6H4 | F | 39f | 75 |
7 | C6H5 | 4-MeOC6H4 | 2-O2NC6H4 | F | 39g | 65 |
8 | 4-MeC6H4 | 3-ClC6H4 | 2-O2NC6H4 | F | 39h | 70 |
9 | 4-MeOC6H4 | 4-FC6H4 | 2-O2NC6H4 | F | 39i | 75 |
10 | 3-MeO-4-FC6H3 | 4-FC6H4 | 2-O2NC6H4 | F | 39j | 72 |
11 | 4-MeOC6H4 | 4-FC6H4 | 2-F-4-O2NC6H3 | F | 39k | 62 |
12 | 4-MeC6H4 | 3-ClC6H4 | 2-F-4-O2NC6H3 | F | 39l | 59 |
13 | 4-MeOC6H4 | 4-FC6H4 | 2,4-(O2N)2C6H3 | Cl | 39m | 70 |
14 | 4-MeC6H4 | 3-ClC6H4 | 2-O2NC6H4 | Cl | 39n | 68 |
15 | 4-iPrC6H4 | C6H5 | 2-O2NC6H4 | F | 39o | 62 |
16 | 2-MeC6H4 | C6H5 | 2-F-4-O2NC6H3 | F | 39p | 69 |
17 | 2-MeC6H4 | C6H5 | 2-F-4-O2NC6H3 | F | 39q | 65 |
18 | 4-O2NC6H4 | C6H5 | 2-F-4-O2NC6H3 | F | 39r | 86 |
19 | 4-FC6H4 | 4-FC6H4 | 2-F-2,4-(O2N)2C6H2 | F | 39s | 93 |
20 | 2-Thienyl | C6H5 | 2-O2NC6H4 | F | 39t | — |
21 | 2-Pyrrolyl | C6H5 | 2-O2NC6H4 | F | 39u | — |
22 | 2-MeC6H4 | C6H5 | 2-O2NC6H4 | Cl | 39v | — |
23 | 4-FC6H4 | 4-FC6H4 | 4-O2NPyridyl | Cl | 39w | — |
24 | 2-MeC6H4 | C6H5 | 2-MeC6H4 | Cl | 39x | — |
Wang et al. prepared nanoparticle-supported tris(triazolyl)–CuBr (Fig. 12), with a diameter of approximately 25 nm and evaluated its catalytic activity in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction (Scheme 17, Table 17, Method A). It was found that the procedure can be successfully extended to various organic azides and alkynes to afford the corresponding 1H-1,2,3-triazoles 41a–q.50
Entry | R1 | R2 | Method | Product | Yield (%) |
---|---|---|---|---|---|
a ![]() |
|||||
1 | C6H5 | C6H13 | A | 41a | 95 |
2 | C6H5 | C8H17 | A | 41b | 91 |
3 | C6H5 | C18H32 | A | 41c | 82 |
4 | C6H5 | C6H5 | A | 41d | 92 |
5 | C6H5 | 4-MeOC6H4 | A | 41e | 83 |
6 | C6H5 | 4-IC6H4 | A | 41f | 81 |
7 | C6H5 | Bn | A | 41g | 96 |
8 | 4-CHOC6H4 | Bn | A | 41h | 96 |
9 | 4-MeOC6H4 | Bn | A | 41i | 94 |
10 | 4-NH2OC6H4 | Bn | A | 41j | 92 |
11 | 2-Pyridyl | Bn | A | 41k | 86 |
12 | 3-Pyridyl | Bn | A | 41l | 92 |
13 | C4H9 | Bn | A | 41m | 99 |
14 | C5H11 | Bn | A | 41n | 93 |
15 | HO–C(CH3) | Bn | A | 41o | 89 |
16 | HO–C(C6H5) | Bn | A | 41p | 93 |
17 | Ferrocenyl | Bn | A | 41q | 96 |
18 | C6H5 | PhOCH2CH(OH)CH2– | B | 41r | 93 |
19 | C6H5 | 2-HOC6H10– | B | 41s | 92 |
20 | C6H5 | CH2![]() |
B | 41t | 83 |
21 | 4-ClC6H4OCH2 | 2,4-Cl2C6H3OCH2CH(OH)CH2– | B | 41u | 80 |
22 | 4-ClC6H4OCH2 | 4-BnC6H4OCH2CH(OH)CH2– | B | 41v | 81 |
23 | Me2C(OH) | 4-MeOC6H4OCH2CH(OH)CH2– | B | 41w | 85 |
24 | Me2C(OH) | PhOCH2CH(OH)CH2– | B | 41x | 91 |
25 | Me2C(OH) | 4-MeOC6H4OCH2CH(OH)CH2– | B | 41y | 93 |
26 | HOCH2 | PhOCH2CH(OH)CH2– | B | 41z | 88 |
27 | BrCH2 | 4-ClC6H4OCH2CH(OH)CH2– | B | 41aa | 86 |
28 | –A | 4-MeOC6H4OCH2CH(OH)CH2– | B | 41ab | 90 |
29 | –A | MeCH2CH(OH)CH2– | B | 41ac | 88 |
30 | –B | 4-MeOC6H4OCH2CH(OH)CH2– | B | 41ad | 93 |
31 | –B | 2-C10H7CH2CH(OH)CH2– | B | 41ae | 92 |
32 | –B | 2-HOC6H10– | B | 41af | 83 |
33 | Ph–C![]() |
2-HOC6H10– | B | 41ag | — |
34 | –B | C10H7OCH2CH(OH)CH2– | C | 41ah | 93 |
35 | –B | 4-MeOC6H4OCH2CH(OH)CH2– | C | 41ai | 92 |
36 | –A | 4-MeOC6H4OCH2CH(OH)CH2– | C | 41aj | 83 |
37 | –A | 4-Cl-3-MeC6H3OCH2CH(OH)CH2– | C | 41ak | 80 |
38 | –A | MeCH2CH(OH)CH2– | C | 41al | 81 |
39 | –C | PhOCH2CH(OH)CH2– | C | 41am | 85 |
40 | –D | nBuOCH2CH(OH)CH2– | C | 41an | 91 |
41 | –D | AllylOCH2CH(OH)CH2– | C | 41ao | 93 |
42 | 4-ClC6H4OCH2 | 2,4-Cl2C6H3OCH2CH(OH)CH2– | C | 41ap | 88 |
43 | 4-ClC6H4OCH2 | 4-BnC6H4OCH2CH(OH)CH2– | C | 41aq | 86 |
44 | 4-O2NC6H4OCH2 | 2-HOC6H10– | C | 41ar | 90 |
45 | C6H5 | PhOCH2CH(OH)CH2– | C | 41as | 88 |
46 | C6H5 | AllylOCH2CH(OH)CH2– | C | 41at | 87 |
47 | Me2C(OH) | 4-BnC6H4OCH2CH(OH)CH2– | C | 41au | 91 |
48 | Me2C(OH) | PhOCH2CH(OH)CH2– | C | 41av | 90 |
49 | –E | 4-Cl-3-MeC6H3OCH2CH(OH)CH2– | C | 41aw | — |
50 | C6H5 | Bn | D | 41g | 98 |
51 | C6H5 | C6H5 | D | 41ax | 97 |
52 | C6H5 | Me | D | 41ay | 92 |
53 | C6H5 | C3H7 | D | 41az | 83 |
54 | C6H5 | C6H13 | D | 41ba | 95 |
55 | C6H5 | C10H24 | D | 41bb | 95 |
56 | C6H5 | C12H25 | D | 41bc | 65 |
57 | C6H5 | C16H33 | D | 41bd | 62 |
58 | C6H5 | C10H20N3 | D | 41be | 60 |
59 | Me2C(OH) | Bn | D | 41bf | 65 |
60 | Me2C(OH) | C6H5 | D | 41bg | 95 |
61 | Me2C(OH) | C3H7 | D | 41bh | 90 |
62 | Me2C(OH) | C6H13 | D | 41bi | 94 |
Rad et al. reported that the 1,3-dipolar cycloaddition of organic azides with terminal alkynes 35 can be catalyzed by doped nano-sized Cu2O on melamine formaldehyde resin (nano-Cu2O MFR) to furnish the corresponding 1,4-disubstituted 1H-1,2,3-triazole adducts 41s–ag in good to excellent yields at room temperature (Scheme 17, Table 17, Method B).51
Nano copper-doped silica cuprous sulfate (CDSCS), proved also to be a highly efficient heterogeneous catalyst for the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles derivatives 41g and 41ah–bj. In this synthetic methodology, CDSCS catalyzes 1,3-dipolar Huisgen cycloaddition of different functionalized β-azido alcohols and alkynes in a (1:
1, v/v) solution of THF/H2O at room temperature (Scheme 17, Table 17, Method C). The catalyst can be easily prepared and reused for many consecutive runs without a significant decrease in its catalytic reactivity.52
Veerakumar et al. used highly dispersed SiO2 supported CuNPs (copper nanoparticles, Fig. 13) as a recyclable heterogeneous nanocatalyst to employ the synthesis of 1,4-disubstituted-1,2,3-triazoles 41az–bi via Huisgen 1,3-dipolar cycloaddition reactions of halides 38, alkynes 35, and sodium azide using DMSO as the solvent (Scheme 17, Table 17, Method D). All the reactions proceed smoothly to give 41 in high yield.53
Nanoparticle-supported tris(triazolyl)–CuBr, with a diameter of approximately 25 nm has been easily prepared, and its catalytic activity was evaluated in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. The catalyst has been applied for the one-pot synthesis of triazoles 41, through a cascade reaction involving benzyl bromides 38, alkynes 35, and sodium azide (Scheme 18, Table 18, Method A).54
Entry | R1 | R2 | X | Method | Product | Yield (%) |
---|---|---|---|---|---|---|
1 | C6H5 | 2-BrC6H4CH2– | Br | A | 41bj | 88 |
2 | C6H5 | 3-IC6H4CH2– | Br | A | 41bk | 87 |
3 | C6H5 | 4-CNC6H4CH2– | Br | A | 41bl | 72 |
4 | C6H5 | 4-O2NC6H4CH2– | Br | A | 41bm | 90 |
5 | C6H5 | 3-MeC6H4CH2– | Br | A | 41bn | 98 |
6 | C6H5 | 1-Me-4-C6H4triazolyl– | Br | A | 41bo | 83 |
7 | C6H5 | C6H4CH2– | Br | B | 41bp | 92 |
8 | C6H5 | 4-HOC6H4CH2– | Br | B | 41bq | 93 |
9 | C6H5 | 4-MeOC6H4CH2– | Br | B | 41br | 91 |
10 | C6H5 | 3-O2NC6H4 | Br | B | 41bs | 89 |
11 | C6H5 | C6H4CH2CH2– | Br | B | 41bt | 81 |
12 | nHexyl | C6H4CH2– | Br | B | 41bu | 72 |
13 | COOEt | C6H4CH2– | Br | B | 41bv | 84 |
14 | 4-MeOC6H4 | C6H4CH2– | Br | B | 41i | 91 |
15 | 4-MeC6H4 | C6H4CH2– | Br | B | 41bw | 85 |
16 | 4-BrC6H4 | C6H4CH2– | Br | B | 41bx | 78 |
17 | C6H5 | cHexyl | Br | B | 41by | 70 |
18 | C6H5 | C6H4CH2– | Cl | B | 41a | 88 |
19 | cHexyl | 4-MeOC6H4CH2– | Cl | B | 41bz | 80 |
20 | C6H5 | C6H4CH2– | Br | C | 41bp | 98 |
21 | C6H5 | C6H4CH2– | Cl | C | 41ca | 99 |
22 | C6H5 | 4-NCC6H4CH2– | Br | C | 41bp | 99 |
23 | C6H5 | 3,5-(MeO)2C6H3CH2– | Br | C | 41bp | 98 |
24 | C6H5 | C6H5CH![]() |
Br | C | 41cb | 94 |
25 | C6H5 | C6H4COCH2– | Cl | C | 41cc | 82 |
26 | C6H5 | EtOOCCH2– | Br | C | 41cd | 98 |
27 | C6H5 | CH3(CH2)8– | I | C | 41ce | 98 |
28 | C6H5 | CH3(CH2)8– | Cl | C | 41cf | 94 |
29 | C6H5 | cHexyl | Br | C | 41cg | 93 |
30 | C6H5 | Indol-3-yl–CH2CH2– | Br | C | 41a | 89 |
31 | C6H5OCH2 | C6H4CH2– | Br | C | 41ch | 76 |
32 | N-Phthalimidyl-CH2 | C6H4CH2– | Br | C | 41ci | 84 |
33 | SiMe3 | C6H4CH2– | Br | C | 41cj | 82 |
34 | CH2CH2CH2C![]() |
C6H4CH2– | Br | C | 41ck | 87 |
35 | C6H5 | C6H4CH2– | Br | C | 41g | 98 |
36 | C6H5 | C6H4CH2– | Cl | C | 41g | 99 |
37 | C6H5 | 4-NCC6H4CH2– | Br | C | 41cbl | 99 |
38 | C6H5 | 3,5-(MeO)2C6H3CH2– | Br | C | 41cm | 98 |
39 | C6H5 | 9-Anthracenyl–CH2– | Br | C | 41cn | 90 |
40 | C6H5 | C6H5CH![]() |
Br | C | 41co | 94 |
41 | C6H5 | C6H4COCH2– | Cl | C | 41cp | 82 |
42 | C6H5 | EtOOCCH2– | Br | C | 41cq | 98 |
43 | C6H5 | CH3(CH2)8– | I | C | 41cr | 98 |
44 | C6H5 | CH3(CH2)8– | Cl | C | 41cs | 91 |
45 | C6H5 | cHexyl | Br | C | 41a | 93 |
46 | C6H5 | Indol-3-yl-CH2CH2– | Br | C | 41ct | 89 |
47 | C6H5OCH2 | C6H4CH2– | Br | C | 41cu | 76 |
48 | 4-MeOC6H4 | C6H4CH2– | Br | C | 41i | 90 |
49 | Pyrid-2-yl | C6H4CH2– | Br | C | 41k | 92 |
50 | N-Phthalimidyl-CH2 | C6H4CH2– | Br | C | 41cv | 84 |
51 | SiMe3 | C6H4CH2– | Br | C | 41cw | 82 |
52 | (CH2)5CH3 | CH3(CH2)8– | I | C | 41cx | 92 |
53 | (CH2)8CH3 | cHexyl | Br | C | 41cy | 89 |
54 | 3-(HC![]() |
C6H4CH2– | Br | C | 41cz | 92 |
55 | (CH2)3C![]() |
C6H4CH2– | Br | C | 41da | 87 |
56 | None | HC![]() |
Cl | C | 41db | 89 |
57 | C6H5 | C6H5 | N2+BF4− | C | 41d | 85 |
58 | C6H5 | 4-MeOC6H4 | N2+BF4− | C | 41e | 75 |
59 | C6H5 | 4-MeOCC6H4 | N2+BF4− | C | 41de | 71 |
60 | C6H5 | 4-NCC6H4– | N2+BF4− | C | 41df | 78 |
61 | C6H5 | 4-O2NC6H4– | N2+BF4− | C | 41dg | 92 |
62 | 4-MeOC6H4 | 4-O2NC6H4– | N2+BF4− | C | 41dh | 88 |
63 | Pyrid-2-yl | 4-O2NC6H4– | N2+BF4− | C | 41di | 91 |
64 | 4-F3CC6H4 | 4-O2NC6H4– | N2+BF4− | C | 41dj | 90 |
65 | SiMe3 | 4-O2NC6H4– | N2+BF4− | C | 41dk | 83 |
66 | C6H5 | C6H5 | N2+BF4− | C | 41d | 85 |
67 | C6H5 | C6H5 | NH2 | D | 41d | 90 |
68 | C6H5 | 4-MeOC6H4 | NH2 | D | 41dl | 95 |
69 | C6H5 | 2-ClC6H4 | NH2 | D | 41dm | 64 |
70 | C6H5 | 3-ClC6H4 | NH2 | D | 41dn | 80 |
71 | C6H5 | 4-ClC6H4 | NH2 | D | 41do | 78 |
72 | C6H5 | 4-MeC6H4 | NH2 | D | 41dp | 90 |
73 | C6H5 | 4-F3CC6H4 | NH2 | D | 41dq | 66 |
74 | C6H5 | 1-Naphthyl | NH2 | D | 41dr | 70 |
75 | (CH2)3CH3 | C6H5 | NH2 | D | 41ds | 93 |
76 | cHexyl | C6H5 | NH2 | D | 41dt | 89 |
77 | C6H5 | C6H5 | NH2 | D | 41d | 92 |
78 | C6H5 | C6H5 | Oxiranyl | C | 41d | 92 |
A graphene based composite material with c-Fe2O3 (Fig. 14) nanoparticles has been synthesized via a simple chemical route and can also serves as an efficient catalyst for one-pot synthesis of a series of 1,4-disubstituted-1,2,3 triazoles 41 via reaction of halides 38, sodium azide and the corresponding alkynes 35 (Scheme 18, Table 18, Method B). It is noticeable that increase of electronic effect in the benzyl moiety increases the yield whereas it decreases with substrates containing electron deficient aromatic halides. The same observation is found when different alkynes are studied.55
Alonso et al. found that copper nanoparticles on activated carbon CuNPs/C can also effectively catalyze the multicomponent synthesis of 1,2,3-triazoles 41 from the reaction of different halides, diazonium salts or amines, with sodium azide and alkynes in water at a low copper loading (Scheme 18, Table 18, Method C).56,57
The same group used CuNPs/C, at a low catalyst loading (0.5 mol%), to promote the multicomponent synthesis of 1,2,3-triazoles from phenylacetylene, sodium azide and epoxides (Scheme 18, Table 18, Method D, entry 78).56,57
Alonso et al. applied also a new strategy in which the alkene 42 was directly mixed with the CuNPs/C, dimethyl(methylthio)-sulfonium tetrafluoroborate DMTSF, and NaN3 in MeCN to produce the corresponding methylsulfanyl azide in only 1 h at room temperature. The subsequent reaction with the alkyne 35 afforded the triazole 41du which represent its synthesis from an alkene 42 in one pot for the first time (Scheme 19).56
Entry | R1 | Y | R2 | Producta | Yield (%) |
---|---|---|---|---|---|
a Reaction carried out using compound 15 (2.5 mmol), 7 (1 mmol), in 3 mL of toluene during 3 h, unless otherwise stated. Yields obtained by Fe2O3 catalysis appeared in paranthesis. | |||||
1 | Me | OMe | 4-BrC6H4 | 43a | 96 (94) |
2 | Me | OMe | 4-NCC6H4 | 43b | 79 |
3 | Me | OMe | Ph | 43c | 85 (82) |
4 | Me | OMe | 4-MeOC6H4 | 43d | 83 |
5 | Me | OMe | 4-HOC6H4 | 43e | 68 |
6 | Me | OMe | 2-naphthyl | 43f | 57 |
7 | Me | OMe | (CH2)5CH | 43g | 80 (79) |
8 | Me | OMe | i-Pr | 43h | 72 (67) |
9 | Me | OEt | 4-BrC6H4 | 43i | 95 |
10 | Me | OEt | 4-MeOC6H4 | 43j | 63 |
11 | Me | Me | 4-MeOC6H4 | 43k | 75 (64) |
12 | Me | OMe | 4-BrC6H4 | 43l | 91 (79) |
Entry | Ar | Products | Method | Yielda (%) |
---|---|---|---|---|
a Isolated yield of the pure product based on aryl aldehyde. | ||||
1 | C6H5 | 44a | A | 92 |
2 | 4-BrC6H4 | 44b | A | 89 |
3 | 4-ClC6H4 | 44c | A | 90 |
4 | 3-ClC6H4 | 44d | A | 86 |
5 | 2-ClC6H4 | 44e | A | 80 |
6 | 4-O2NC6H4 | 44f | A | 87 |
7 | 4-MeOC6H4 | 44g | A | 81 |
8 | 4-HOC6H4 | 44h | A | 93 |
9 | 4-CH3C6H4 | 44i | A | 90 |
10 | 4-NCC6H4 | 44j | A | 90 |
11 | C6H5–CH![]() |
44k | A | 86 |
12 | C7H5O | 44l | A | 92 |
13 | 2-Furyl | 44m | A | 50 |
14 | 2-Thienyl | 44n | A | 90 |
15 | C6H12O | 44o | A | 95 |
16 | C6H5 | 44a | B | 85 |
17 | 4-BrC6H4 | 44b | B | 88 |
18 | 4-ClC6H4 | 44c | B | 90 |
19 | 4-HOC6H4 | 44h | B | 83 |
20 | 4-MeOC6H4 | 44g | B | 90 |
21 | 4-MeC6H4 | 44p | B | 92 |
22 | 3-O2NC6H4 | 44q | B | 78 |
23 | 4-O2NC6H4 | 44f | B | 73 |
Mirzaei and Davoodnia used a microwave-assisted sol–gel method to synthesize nano-sized MgO particles using Mg(NO3)2·6H2O as precursor and deionized water as solvent. The catalytic behavior of the catalyst was investigated in the one-pot synthesis of Hantzsch 1,4-dihydropyridines 44a–c, 44f–h, and 44p, 44q (Scheme 21, Table 20, Method B). The reaction proceeded in good to high yields from the reaction of aromatic aldehydes, ethylacetoacetate, and ammonium acetate.60
A reaction mechanism is proposed and postulated that in MgO nanoparticles, there are acid-base bifunctional sites where Mg and O act as a weak Lewis acidic site and relatively high strength Brönsted basic site, respectively. These acid-base bifunctional sites facilitate the formation of arylidene and enamine intermediates that then react to give the final products.
Entry | R1 | R2 | Products | Yield (%) |
---|---|---|---|---|
1 | C6H5 | C6H5 | 45a | 96 |
2 | C6H5 | 4-BrC6H4 | 45b | 94 |
3 | C6H5 | 4-ClC6H4 | 45c | 91 |
4 | 4-NCC6H4 | C6H5 | 45d | 92 |
5 | 4-NCC6H4 | 4-ClC6H4 | 45e | 95 |
6 | 4-MeC6H4 | 4-MeC6H4 | 45f | 95 |
7 | 4-MeC6H4 | C6H5 | 45g | 91 |
8 | 4-MeC6H4 | 4-BrC6H4 | 45h | 92 |
9 | 4-MeC6H4 | 4-O2NC6H4 | 45i | 95 |
10 | 4-MeC6H4 | 4-MeC6H4 | 45j | 92 |
11 | 3-O2NC6H4 | C6H5 | 45k | 90 |
12 | 4-MeOC6H4 | 4-ClC6H4 | 45l | 93 |
13 | 4-ClC6H4 | 4-BrC6H4 | 45m | 90 |
14 | 4-ClC6H4 | 4-MeC6H4 | 45n | 93 |
15 | 4-ClC6H4 | C6H5 | 45o | 91 |
16 | 4-MeOC6H4 | 4-MeC6H4 | 45p | 92 |
17 | 4-MeOC6H4 | C6H5 | 45q | 90 |
18 | 4-MeOC6H4 | 4-BrC6H4 | 45r | 94 |
19 | C6H5 | 4-IC6H4 | 45s | 91 |
20 | 4-ClC6H4 | 4-BrC6H4 | 45t | 92 |
21 | 4-NCC6H4 | 4-BrC6H4 | 45u | 91 |
Entry | R1 | R2 | Method | Product | Yieldab (%) |
---|---|---|---|---|---|
a Method A Yields were analyzed by GC.b Method B yield refer to those of pure isolated products. | |||||
1 | C6H5 | 4-MeC6H4 | A | 47a | 82 |
2 | 4-ClC6H4 | 4-MeC6H4 | A | 47b | 87 |
3 | 3-ClC6H4 | 4-MeC6H4 | A | 47c | 85 |
4 | 4-BrC6H4 | 4-MeC6H4 | A | 47d | 83 |
5 | 3-BrC6H4 | 4-MeC6H4 | A | 47e | 83 |
6 | 3-O2NC6H4 | 4-MeC6H4 | A | 47f | 81 |
7 | 4-O2NC6H4 | 4-MeC6H4 | A | 47g | 82 |
8 | 4-MeOC6H4 | 4-MeC6H4 | A | 47h | 85 |
9 | C6H5 | C6H5 | B | 47i | 91 |
10 | C6H5 | 4-ClC6H4 | B | 47j | 81 |
11 | C6H5 | 4-MeOC6H4 | B | 47k | 79 |
12 | C6H5 | 4-MeC6H4 | B | 47a | 84 |
13 | 4-MeC6H4 | C6H5 | B | 47l | 81 |
14 | 4-ClC6H4 | C6H5 | B | 47m | 87 |
15 | 4-ClC6H4 | 4-MeC6H4 | B | 47b | 80 |
16 | 2-Naphthyl | C6H5 | B | 47n | 79 |
17 | 2-Pyridinyl | C6H5 | B | 47o | 89 |
18 | 2-Phenylpropanal | C6H5 | B | 47p | 88 |
19 | Me | C6H5 | B | 47q | 90 |
20 | C6H5 | n-Bu | B | 47r | 83 |
2-Hydroxyethylammonium sulphonate immobilized on -Fe2O3 nanoparticles (-Fe2O3-2-HEAS, Fig. 16) was synthesized as a new supported ionic liquid by the reaction of n-butylsulfonated-Fe2O3 with ethanolamine. This catalyst also efficiently promoted the synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines 47 in good to high yields under solvent-free conditions (Scheme 23, Table 22, Method B+). The catalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least five times without significant degradation in the activity.63
Entry | R | X | R1 | Product | Time/yield (%) MWa | Time/yield (%) Δb |
---|---|---|---|---|---|---|
a Using microwave irradiation.b Under classical heating conditions. | ||||||
1 | Ph | O | OEt | 49a | 4/97 | 30/95 |
2 | 3-ClC6H4 | O | OEt | 49b | 4/98 | 25/97 |
3 | 4-O2NC6H4 | O | OEt | 49c | 4/98 | 30/97 |
4 | 2-Thienyl | O | OEt | 49d | 4/98 | 25/98 |
5 | 2-FC6H4 | O | OEt | 49e | 4/97 | 35/92 |
6 | 3,4-(OMe)2C6H3 | O | OEt | 49f | 4/99 | 20/98 |
7 | 4-MeC6H4 | S | OEt | 49g | 4/95 | 40/90 |
8 | Ph | S | OEt | 49h | 4/97 | 35/96 |
9 | 2-Thienyl | S | OEt | 49i | 4/95 | 25/95 |
10 | Ph | O | Me | 49j | 4/97 | 30/95 |
11 | Ph | S | Me | 49k | 4/96 | 30/93 |
12 | 4-MeC6H4 | S | Me | 49l | 4/95 | 35/92 |
Entry | Ar | X | Producta | Time (h) | Yieldb (%) |
---|---|---|---|---|---|
a Reaction conditions: aromatic aldehyde (1 mmol), cyclopentanone (1 mmol), urea or thiourea (1.2 mmol) in solvent-free at 70 °C.b Isolated yield. | |||||
1 | C6H5 | O | 54a | 0.75 | 95 |
2 | 2-ClC6H4 | O | 54b | 1.5 | 86 |
3 | 4-ClC6H4 | O | 54c | 1.25 | 84 |
4 | 4-FC6H4 | O | 54d | 1.25 | 83 |
5 | 4-BrC6H4 | O | 54e | 1.25 | 89 |
6 | 4-MeC6H4 | O | 54f | 1 | 94 |
7 | 4-MeOC6H4 | O | 54g | 1 | 93 |
8 | 3-O2NC6H4 | O | 54h | 2.5 | 83 |
9 | 2-Naphthyl | O | 54i | 1.5 | 82 |
10 | C6H5 | S | 54j | 1 | 96 |
11 | 2-ClC6H4 | S | 54k | 2 | 86 |
12 | 4-ClC6H4 | S | 54l | 1.5 | 92 |
13 | 4-FC6H4 | S | 54m | 1.6 | 86 |
14 | 4-BrC6H4 | S | 54n | 1.4 | 89 |
15 | 4-MeC6H4 | S | 54o | 1 | 91 |
16 | 4-MeOC6H4 | S | 54p | 1 | 93 |
17 | 3-O2NC6H4 | S | 54q | 3.5 | 79 |
18 | 4-O2NC6H4 | S | 54r | 3 | 91 |
19 | 2-Naphthyl | S | 54s | 1.5 | 87 |
Entry | R | Product | Method | Yield (%) |
---|---|---|---|---|
1 | C6H5 | 56a | A | 92 |
2 | 4-FC6H4 | 56b | A | 96 |
3 | 4-ClC6H4 | 56c | A | 97 |
4 | 3-O2NC6H4 | 56d | A | 98 |
5 | 4-O2NC6H4 | 56e | A | 88 |
6 | 4-MeOC6H4 | 56f | A | 5 |
7 | 4-MeC6H4 | 56g | A | 87 |
8 | 2-ClC6H4 | 56h | A | 83 |
9 | 4-HOC6H4 | 56i | A | 92 |
10 | 2-O2NC6H4 | 56j | A | 77 |
11 | CH![]() |
56k | A | Trace |
12 | CH2CH2C6H4 | 56l | A | Trace |
13 | C6H5 | 56a | B | 98 |
14 | 4-MeOC6H4 | 56f | B | 73 |
15 | 4-MeC6H4 | 56g | B | 93 |
16 | 4-Me2NC6H4 | 56m | B | 90 |
17 | 2-ClC6H4 | 56h | B | 86 |
18 | 4-ClC6H4 | 56c | B | 94 |
19 | 4-BrC6H4 | 56n | B | 90 |
20 | 2-O2NC6H4 | 56j | B | 83 |
21 | 3-O2NC6H4 | 56d | B | 98 |
22 | 4-O2NC6H4 | 56e | B | 97 |
23 | 2-FC6H4 | 56o | B | 90 |
24 | CH3CH2CH2 | 56p | B | 70 |
25 | Furan-2-yl | 56q | B | 93 |
26 | CH![]() |
56k | B | 71 |
27 | C6H5 | 56a | C | 97 |
28 | 4-MeOC6H4 | 56f | C | 89 |
29 | 4-MeC6H4 | 56g | C | 93 |
30 | 4-Me2NC6H4 | 56m | C | 95 |
31 | 2-ClC6H4 | 56h | C | 86 |
32 | 4-ClC6H4 | 56c | C | 94 |
33 | 4-BrC6H4 | 56n | C | 93 |
34 | 2-O2NC6H4 | 56j | C | 88 |
35 | 3-O2NC6H4 | 56d | C | 95 |
36 | 4-O2NC6H4 | 56e | C | 94 |
37 | C6H5 | 56a | D | 94 |
38 | 2-ClC6H4 | 56h | D | 97 |
39 | 2-BrC6H4 | 56r | D | 94 |
40 | 4-ClC6H4 | 56c | D | 98 |
41 | 4-BrC6H4 | 56n | D | 96 |
42 | 3-ClOC6H4 | 56s | D | 96 |
43 | 4-FC6H4 | 56b | D | 98 |
44 | 2-ClC6H4 | 56h | D | 96 |
25 | 2-O2NC6H4 | 56j | D | 95 |
46 | 4-O2NC6H4 | 56e | D | 93 |
47 | 4-NCOC6H4 | 56t | D | 95 |
48 | 3-HOC6H4 | 56u | D | 90 |
49 | 2-Naphthyl | 56v | D | 97 |
50 | 1-Naphthyl | 56w | D | 92 |
51 | 2-Furyl | 56x | D | 94 |
52 | 2-Thienyl | 56y | D | 96 |
53 | 4-OHCC6H4 | 56i | D | 98 |
54 | 4-OHCC6H4 | 56i | D | 98 |
55 | Et | 56z | D | 88 |
56 | nPr | 56aa | D | 86 |
Azarifar et al. used nano-titania-supported Preyssler-type heteropolyacid, n-TiO2/H14[NaP5W30O110] as an efficient and reusable heterogeneous catalyst for the synthesis of highly functionalized 4H-chromenes 56 under ultrasound irradiation conditions (Scheme 28, Table 26, Method B).69
The same group reported also the synthesis of highly functionalized 4H-chromenes 56 in the presence of nano-titania sulfuric acid (15 nm TSA) as a heterogeneous catalyst (Scheme 28, Table 26, Method C).70
As shown in Table 26, the ease of the reaction is directly related to the substituents attached to the benzene ring and the spatial accessibility of aldehyde 7 as well. The electron withdrawing groups were found to activate the aldehyde toward nucleophilic attack and increase the reaction rate (entry 10, 11).
Sarrafi et al. demonstrated a similar approach for the synthesis of 4H-chromene derivatives 56 in excellent yields using mesoporous silica nanoparticles as a bio-compatible, and recoverable catalyst (Scheme 28, Table 26, Method D).71
CuFe2O4 magnetic nanoparticles were synthesized and recognized as an efficient catalyst for the one-pot synthesis of 4H-chromene derivatives 57 in aqueous medium at mild conditions and in excellent yields. The reaction proceeds via MCR's of dimedone or cyclohexane-1,3-dione, 55 dialkyl acetylenedicarboxylates 8 and malononitrile or ethyl cyanoacetate 46 (Scheme 29, Table 27).72
Entry | R1 | R2 | R3 | Product | Time (h) | Yield (%) |
---|---|---|---|---|---|---|
1 | Me | Et | CN | 57a | 2 | 92 |
2 | Me | Et | CO2Et | 57b | 2.5 | 88 |
3 | Me | Me | CN | 57c | 2 | 91 |
4 | Me | Me | CO2Et | 57d | 2.5 | 86 |
5 | H | Et | CN | 57e | 2 | 94 |
6 | H | Et | CO2Et | 57f | 2.5 | 89 |
7 | H | Me | CN | 57g | 2 | 92 |
8 | H | Me | CO2Et | 57h | 2.5 | 86 |
Pradhan et al. proposed a possible mechanism (Scheme 3) for this 3 CRs. Thus, Cu2+ of CuFe2O4 catalyzed the Michael addition reaction of dialkyl acetylene dicarboxylate with alkyl nitrile derivatives (malononitrile and ethyl cyanoacetate) during the formation of the intermediate X. The nucleophilic attack by the intermediate Y at the β position (with respect to nitrile group) of the intermediate X was enhanced by Cu2+ may be due to the polarization of the π-electron cloud. Finally, the Lewis acidic Fe3+ interacted with enolate intermediate Z which in turn facilitates intramolecular electrophilic cyclization with the formation of the six member ring (P) (Scheme 30).72
Sarrafi et al. investigated the synthesis of spiro[(4H-chromene)-4,3′-oxindoles] 59a–s by three component reaction of an isatin, malononitrile, and cyclic 1,3-diketones in ethanol at 60 °C using mesoporous silica nanoparticles as a catalyst (Scheme 31, Table 28, Method A).71
Entry | R1 | R2 | R | Product | Method | Yield (%) |
---|---|---|---|---|---|---|
1 | H | H | Me | 59a | A | 98 |
2 | H | H | H | 59b | A | 97 |
3 | H | H | Me | 59c | A | 95 |
4 | H | H | H | 59d | A | 96 |
5 | H | Bn | Me | 59e | A | 93 |
6 | H | Bn | H | 59f | A | 95 |
7 | 5-Br | H | Me | 59g | A | 97 |
8 | 5-Br | H | H | 59h | A | 98 |
9 | 5-Me | H | Me | 59i | A | 95 |
10 | 5-Me | H | H | 59j | A | 94 |
11 | 5-O2N | H | Me | 59k | A | 96 |
12 | 5-O2N | H | H | 59l | A | 97 |
13 | 5-Br | H | Me | 59e | A | 96 |
14 | 5-Br | H | H | 59h | B | 96 |
15 | H | H | H | 59d | B | 98 |
16 | H | NO2 | H | 59m | B | 94 |
17 | H | Me | H | 59n | B | 92 |
18 | H | Cl | H | 59o | B | 97 |
19 | H | Br | H | 59p | B | 91 |
20 | Me | H | H | 59q | B | 96 |
21 | H | H | Me | 59a | B | 97 |
22 | H | NO2 | Me | 59r | B | 93 |
23 | H | Cl | Me | 59s | B | 90 |
Hosseini-Sarvari and Tavakolian also synthesized spirooxindole derivatives 59 by a one-pot, three-component reaction of 55, 58 and 46 in excellent yield at room temperature under solvent-free conditions in the presence of 10 mol% ZnO nano-rods catalyst by a very simple procedure (using a mortar and the mixture was ground by a pestle at room temperature) (Scheme 31, Table 28, Method B). All of the reactions provided the desired spirooxindole products in excellent yields employing both electron-deficient (entries 2, 4, and 5) and electron-rich (entry 3) isatins as substrates.73
The nano ZnO has Lewis acid (Zn2+) and Lewis basic (O2−) sites.74 In the first step (i) a Lewis acid site (Zn2+) is coordinated to O-atom of the CO group of isatin, resulting in the increase of its reactivity.75
Entry | R | Product | Yielda (%) |
---|---|---|---|
a Yield refers to isolated products. | |||
1 | C6H5 | 60a | 96 |
2 | 4-BrC6H4 | 60b | 94 |
3 | 3-BrC6H4 | 60c | 90 |
4 | 4-ClC6H4 | 60d | 92 |
5 | 2-ClC6H4 | 60e | 90 |
6 | 3-ClC6H4 | 60f | 90 |
7 | 4-(CH3)2NC6H4 | 60g | 80 |
8 | 2-MeOC6H4 | 60h | 93 |
9 | 2-FC6H4 | 60i | 90 |
10 | 4-NO2C6H4 | 60j | 88 |
11 | 2-NO2C6H4 | 60k | 82 |
12 | 4-MeC6H5 | 60l | 92 |
13 | 4-OHC6H5 | 60m | 86 |
14 | C6H5CH![]() |
60n | 90 |
15 | 2-Thienyl | 60o | 89 |
16 | 3-Thienyl | 60p | 91 |
17 | 2-Furyl | 60q | 90 |
18 | 3-Pyridyl | 60r | 89 |
19 | C4H8O | 60s | 84 |
The bimetallic ZnFe2O4 nanopowder, a dual Lewis acid–base combined catalyst, is found to efficiently catalyze a four component reaction for the synthesis of functionalized tetrahydrospiro[indoline-3,2′-quinoline] derivatives 61a–ae. Thus, reaction of arylamines 9, dialkyl acetylene dicarboxylates 8, isatin derivatives 58 and cyclohexane-1,3-diones 55 in water medium at room temperature afforded 61 in good yields (Scheme 33, Table 30).77 A probable mechanism for the formation of 61 depends on the dual role of ZnFe2O4 as a Lewis acidic site, as well as basic site.78
Entry | R1 | R2 | R3 | R4 | R5 | Product | Yield (%) |
---|---|---|---|---|---|---|---|
1 | H | H | 4-MeC6H4 | Me | Me | 61a | 77 |
2 | H | H | 4-MeOC6H4 | Et | Me | 61b | 75 |
3 | H | H | 4-BrC6H4 | Me | Me | 61c | 72 |
4 | H | H | 4-BrC6H4 | Et | Me | 61d | 73 |
5 | Et | H | 4-MeOC6H4 | Me | Me | 61e | 80 |
6 | Et | H | 4-ClC6H4 | Me | Me | 61f | 78 |
7 | H | Br | 4-MeOC6H4 | Me | Me | 61g | 71 |
8 | Et | Cl | 4-MeOC6H4 | Et | H | 61h | 77 |
9 | H | Cl | 4-BrC6H4 | Me | Me | 61i | 69 |
10 | Pr | H | 4-MeOC6H4 | Me | Me | 61j | 72 |
11 | H | Cl | 4-ClC6H4 | Et | Me | 61k | 76 |
12 | Pr | Cl | 4-MeOC6H4 | Me | Me | 61l | 81 |
13 | Pr | Cl | 4-MeC6H4 | Et | Me | 61m | 72 |
14 | Pr | H | 4-ClC6H4 | Me | H | 61n | 70 |
15 | H | H | 4-MeOC6H4 | Et | H | 61o | 74 |
16 | Pr | Cl | 4-ClC6H4 | Me | H | 61p | 76 |
17 | H | F | 4-MeOC6H4 | Et | H | 61q | 78 |
18 | H | Br | 4-ClC6H4 | Et | Me | 61r | 73 |
19 | Et | Cl | 4-FC6H4 | Et | H | 61s | 79 |
20 | H | Cl | 4-MeC6H4 | Et | Me | 61t | 82 |
21 | H | H | 3-ClC6H4 | Et | Me | 61u | 67 |
22 | H | H | 3-MeOC6H4 | Et | Me | 61v | 70 |
23 | H | Cl | 3-ClC6H4 | Et | Me | 61w | 69 |
24 | H | H | 4-ClC6H4 | Me | Me | 61x | 77 |
25 | H | Cl | 4-MeOC6H4 | Me | Me | 61y | 73 |
26 | H | Cl | C6H5 | Me | Me | 61z | 67 |
27 | H | Cl | 4-MeOC6H4 | Et | Me | 61a | 78 |
28 | H | H | 4-MeOC6H4 | Me | Me | 61b | 78 |
29 | H | H | C6H5 | Me | Me | 61c | 73 |
30 | H | H | 4-ClC6H4 | Et | Me | 61d | 79 |
31 | H | H | 4-MeC6H4 | Et | Me | 61e | 82 |
Entry | R-NH2 | R1 | Product | R | Yield (%) |
---|---|---|---|---|---|
1 | C6H5CH2– | H | 63a | C6H5 | 92 |
2 | 3-HOC6H4CH2– | H | 63b | 3-HOC6H4 | 84 |
3 | 4-MeOC6H4CH2– | H | 63c | 4-MeOC6H4 | 89 |
4 | 4-FC6H4CH2– | H | 63d | 4-FC6H4 | 85 |
5 | 4-BrC6H4CH2– | H | 63e | 4-BrC6H4 | 78 |
6 | 2-Naphthyl–CH2– | H | 63f | 2-Naphthyl | 90 |
7 | 3-Pyridyl–CH2– | H | 63g | 3-Pyridyl | 87 |
8 | 3,5-(MeO)2C6H3CH2– | H | 63h | 3,5-(MeO)2C6H3 | 81 |
9 | C6H5CH2– | 2-Me | 63i | C6H5 | 84 |
10 | C6H5CH2– | 3-Cl | 63j | C6H5 | 80 |
11 | C6H5CH2– | 3,4-Me2 | 63k | C6H5 | 90 |
12 | C6H5CH2– | 3-Cl | 63l | C6H5 | 86 |
13 | C6H5CH2– | 2-Me-3-Cl | 63m | C6H5 | 83 |
The plausible reaction mechanism depends on the basis that Cu ferrite NPs provide the surface for the simultaneous oxidation and reduction of the reactants.80 Benzyl amine on autoxidation forms corresponding benzaldehyde and releases the ammonia which was confirmed by the litmus paper test after the workup of the reaction. Here ammonia acts as a hydrogen source for the reduction of the nitro group of the o-nitro phenol. It reduces to 2-amino phenol which was then condensed with the benzaldehyde and gives the 2-phenylbenzo[d]oxazole (Scheme 35).
Tang et al. described a one-pot direct synthesis of benzoxazoles 63 using o-nitrophenols 62 and alcohols 64 as the starting materials catalyzed by gold nanoparticles supported on titanium dioxide (Au/TiO2) (Scheme 36). The products were obtained in good yields and yields are summarized in Table 32 The electronic properties of a series of benzylic alcohols were found to have little influence on the reaction. Reactions with benzylic alcohols bearing both electron-donating groups (Table 32, entries 2–5) and electron-withdrawing groups (Table 32, entries 8–10) in the aromatic ring could effectively afford the desired products in excellent yields. However, the steric hindrance of the substituents had a negative influence on the reaction. Relatively low yields of the corresponding products were obtained when the substituent groups appeared in the ortho-position of the benzene ring (Table 32, entries 6 and 7).81
Entry | R | R1 | Product | Yield (%) |
---|---|---|---|---|
1 | C6H5 | H | 63a | 99(90) |
2 | 4-MeC6H4 | H | 63n | 98 |
3 | 3-MeC6H4 | H | 63o | 97 |
4 | 4-MeOC6H4 | H | 63p | 99(91) |
5 | 3-MeOC6H4 | H | 63q | 91 |
6 | 2-MeC6H4 | H | 63r | 81 |
7 | 2-MeOC6H4 | H | 63s | 85 |
8 | 4-FC6H4 | H | 63d | 95(85) |
9 | 3-FC6H4 | H | 63t | 94 |
10 | 4-ClC6H4 | H | 63u | 98 |
11 | 4-BrC6H4 | H | 63e | 63/17 |
12 | 4-CF3C6H4– | H | 63v | 70 |
13 | 1-Naphthyl | H | 63w | 95 |
14 | Me | H | 63x | 52 |
15 | tBu | H | 63y | 63(55) |
16 | nC5H11 | H | 63z | 56 |
17 | Cyclohexyl | H | 63aa | 60 |
18 | C6H5 | 4-Me | 63ab | 96 |
19 | C6H5 | 5-Me | 63ac | 95(84) |
20 | C6H5 | 4-MeO | 63ad | 97 |
21 | C6H5 | 5-F | 63ae | 98 |
22 | C6H5 | 4-F | 63af | 99 |
23 | C6H5 | 4-Cl | 63ag | 95 |
24 | C6H5 | H | 63a | 80(75) |
The authors suggested a possible mechanism for the reaction as depicted in Scheme 37. First of all, dehydrogenative oxidation of the alcohol 64 to its corresponding carbonyl compound generates the gold-hydride species (b) and 2-nitrophenol (62) is reduced to 2-aminophenol in situ by b. This is the first hydrogen-transfer process. Then, the aldehyde can readily react with 2-aminophenol to afford the corresponding imine (c). c is selectively converted to the intermediate 2-phenyl-2,3-dihydrobenzoxazole (d) under the catalysis of a gold catalyst. Subsequently, d can be rapidly oxidized to the product 63 in the presence of a gold catalyst accompanied by the generation of b and 2-nitrophenol (62) is reduced to 2-aminopheno by b. This is the second hydrogen-transfer process. In the whole catalytic cycle, the alcohol and the intermediate 2-phenyl-2,3-dihydrobenzoxazole are used as reductants (hydrogen donor) once and 2-nitrophenol is used as the oxidant (hydrogen acceptor) twice.81
Entry | R | R1 | Product | Yield (%) |
---|---|---|---|---|
1 | C6H5 | H | 65a | 95 |
2 | 4-ClC6H4 | H | 65b | 97 |
3 | 2-BrC6H4 | H | 65c | 97 |
4 | 4-MeC6H4 | H | 65d | 95 |
5 | 3-O2NC6H4 | 4-Me | 65e | 89 |
6 | 1-Naphthyl | 4-Me | 65f | 93 |
7 | 1-Naphthyl | 4-Cl | 65g | 88 |
8 | 9-Anthryl | H | 65h | 92 |
9 | 3-Pyridyl | H | 65i | 91 |
10 | 3-Indolyl | 4-Me | 65j | 92 |
11 | 2-Thienyl | H | 65k | 92 |
The same authors has also achieved an efficient synthesis of bis-benzimidazoles 66, from terephthaldialdehyde using this catalytic system (Scheme 39).82
A highly efficient and selective reaction for the synthesis of 2-substituted benzimidazoles 68 using o-nitroanilines 67 and alcohols 64 as the starting materials catalyzed by Au/TiO2 has been developed via two hydrogen-transfer processes (Scheme 40, Table 34). This reaction has a good tolerance to air and water, a wide substrate scope, and represents a new avenue for practical C–N and C–O bond formation. More importantly, no additional additives, oxidants and reductants are required for the reaction and the catalyst can be recovered and reused readily.81
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
1 | C6H5 | H | 68a | 78(70) |
2 | C6H5 | Me | 68b | 84 |
3 | 4-MeC6H4 | Me | 68c | 83 |
4 | 4-MeOC6H4 | Me | 68d | 86(81) |
5 | 4-FC6H4 | Me | 68e | 86 |
6 | 4-ClC6H4 | Me | 68f | 79(70) |
Entry | Ar | Product | Method | Yield (%) |
---|---|---|---|---|
1 | 4-ClC6H5 | 69a | A | 97 |
2 | 2,4-Cl2C6H3 | 69b | A | 96 |
3 | 3,4-(MeO)2C6H3 | 69c | A | 93 |
4 | 4-MeC6H4 | 69d | A | 98 |
5 | 3-MeOC6H4 | 69e | A | 96 |
6 | 3-O2NC6H4 | 69f | A | 87 |
7 | 1-Naphthyl | 69g | A | 93 |
8 | 3-Pyridyl | 69h | A | 92 |
9 | 3-indolyl | 69i | A | 94 |
10 | 2-Thienyl | 69j | A | 92 |
11 | C6H5 | 69k | B | 90 |
12 | 2-ClC6H4 | 69l | B | 84 |
13 | 4-ClC6H4 | 69a | B | 86 |
14 | 2-HOC6H4 | 69m | B | 82 |
15 | 4-HOC6H4 | 69n | B | 83 |
16 | 4-FC6H4 | 69o | B | 86 |
17 | 4-BrC6H4 | 69p | B | 86 |
18 | 4-MeC6H4 | 69d | B | 90 |
19 | 4-MeOC6H4 | 69q | B | 93 |
20 | 2-O2NC6H4 | 69r | B | 81 |
21 | 3-O2NC6H4 | 69f | B | 86 |
22 | 4-O2NC6H4 | 69s | B | 89 |
23 | 2-Naphthyl | 69t | B | 90 |
24 | Furyl | 69u | B | 79 |
Rahmani et al. prepared nano titania-supported sulfonic acid (n-TSA) from the reaction of nano titania (titanium oxide) with chlorosulfonic acid as sulfonating agent. This was efficiently used as a heterogeneous catalyst for synthesis of 2-arylbenzothiazoles 69, via reaction of aromatic aldehyde with 2-aminothiophenol in solvent-free at 70 °C (Scheme 41, Table 35, Method B).67
Nasr-Esfahani et al. prepared symmetrical bis-benzothiazole 70 in high yield by the reaction of terephthaldialdehyde 7 with two equivalents of 2-aminothiophenol 9 in the presence of a catalytic amount of Cu(II)-TD@nSiO2 under conventional conditions (Scheme 42).82
Entry | R | R1 | Product | Yield (%) |
---|---|---|---|---|
1 | H | Me | 71a | 90 |
2 | 3-OH | Me | 71b | 93 |
3 | 3,5-(OH)2 | Me | 71c | 89 |
4 | 3-MeO | Me | 71d | 93 |
5 | 3-OH-2-Me | Me | 71e | 86 |
6 | 3-NH2 | Me | 71f | 89 |
7 | 4-O2N | Me | 71g | 92 |
8 | 4-Cl | Me | 71h | 73 |
9 | 3-OH | Ph | 71i | 88 |
10 | 3,5-(OH)2 | Ph | 71j | 85 |
11 | 3-MeO | Ph | 71k | 87 |
12 | 3,5-(Me)2 | Ph | 71l | 85 |
Mohammad and Kassaee reported the use of sulfochitosan-coated Fe3O4 magnetic nanoparticles (Fe3O4@CS–SO3H NPs, Fig. 20) as a “green” heterogeneous catalyst for preparation of 2-amino-4H-chromen-4-yl phosphonates 72c–k through one-pot, three-component reactions of salicylaldehydes 7, malononitrile 46, and triethyl phosphite in water at room temperature (Scheme 45, Table 37).85
Entry | R1 | Product | Yield (%) |
---|---|---|---|
1 | H | 72c | 93 |
2 | 6-Cl | 72d | 96 |
3 | 6-O2N | 72e | 92 |
4 | 6-Me | 72f | 95 |
5 | 6-Br | 72g | 97 |
6 | 7-MeO | 72h | 93 |
7 | 6,8-Br2 | 72i | 97 |
8 | 6,8-Br2 | 72j | 94 |
9 | 6-MeO | 72k | 88 |
Entry | R1 | Product | Yield (%) |
---|---|---|---|
1 | C6H5 | 73a | 99 |
2 | 4-FC6H4 | 73b | 99 |
3 | 4-MeOC6H4 | 73c | 98 |
4 | Me | 73d | 99 |
Entry | R1 | R2 | R3 | Product | Yield (%) |
---|---|---|---|---|---|
1 | H | C6H5 | C6H5 | 75a | 90 |
2 | H | 4-Fluorophenyl | C6H5 | 75b | 88 |
3 | H | 4-Bromophenyl | C6H5 | 75c | 83 |
4 | H | p-Tolyl | C6H5 | 75d | 82 |
5 | H | 2,5-DiMephenyl | C6H5 | 75e | 71 |
6 | H | Mesityl | C6H5 | 75f | 0 |
7 | H | Et | C6H5 | 75g | 84 |
8 | H | nBu | C6H5 | 75h | 95 |
9 | H | Hexadecyl | C6H5 | 75i | 78 |
10 | H | iPr | C6H5 | 75j | 90 |
11 | H | tBu | C6H5 | 75k | 89 |
12 | H | Cyclopropyl | C6H5 | 75l | 90 |
13 | H | Cyclopropyl | C6H5 | 75l | 74 |
14 | H | C6H5 | C6H5 | 75m | 73 |
15 | 6-Cl | C6H5 | C6H5 | 75a | 85 |
16 | 6-Br | C6H5 | C6H5 | 75n | 93 |
17 | 6,7-DiMe | C6H5 | C6H5 | 75o | 63 |
18 | 6-Cl | C6H5 | C6H5 | 75p | 45 |
19 | H | C6H5 | p-Tolyl | 75q | 89 |
20 | H | C6H5 | m-Tolyl | 75r | 86 |
21 | H | C6H5 | o-Tolyl | 75s | 94 |
22 | H | C6H5 | 4-Methoxyphenyl | 75t | 88 |
23 | H | C6H5 | Benzo[1,3]dioxol-5-yl | 75u | 58 |
24 | H | C6H5 | 4-Chlorophenyl | 75v | 87 |
25 | H | C6H5 | 4-Fluorophenyl | 75w | 91 |
26 | H | C6H5 | 4-(Trifluoromethyl)phenyl | 75x | 92 |
27 | H | C6H5 | 1-Naphthyl | 75y | 86 |
28 | H | C6H5 | 2-Furyl | 75z | 51 |
A postulated reaction pathway is proposed, as shown in Scheme 48. Firstly, CuO NPs may activate 2-aminobenzophenone to generate intermediate I. Meanwhile, benzylic amine can attach to the surface of the CuO NPs to form intermediate II. In the intermediate II, the distance between 2-aminobenzophenone and benzylic amine may be shortened, facilitating the attack of benzylic amine to 2-aminobenzophenone. After attacked by benzylic amine, imine A is formed. A subsequently undergoes an oxidation process and is stabilized by CuO NPs (intermediate III). Intramolecular attack of the amino-group to the imine cation results in intermediate B. Further oxidation of intermediate B gives the quinazoline product.86
Tang et al. developed a highly efficient and selective nitrogen source-promoted reaction for the synthesis of 2,4-disubstituted quinazolines 75 from o-nitroacetophenones 76 and alcohols 64 catalyzed by Au/TiO2 via a hydrogen-transfer strategy (Scheme 49, Table 40). This reaction has good tolerance to air and water, a wide substrate scope, and represents a new avenue for practical multiple C–N bond formation. More importantly, no additional additive, oxidant and reductant are required in the reaction and the catalyst can be recovered and reused readily. The electronic properties of a series of aromatic alcohols were found to have little influence on the reaction. The reactions could be carried out effectively to afford the desired products with good yields regardless of the electron-donating groups or electron-withdrawing groups at the benzene ring of benzylic alcohols. However, the steric hindrance of the substituents had a negative influence on the reaction.87
Entry | R1 | R2 | R3 | Yield (%) |
---|---|---|---|---|
a Under air.b 150 °C. | ||||
1 | H | Me | C6H5 | 99(83)a |
2 | H | Me | 4-MeC6H4 | 97(80)a |
3 | H | Me | 4-MeOC6H4 | 95 |
4 | H | Me | 2-MeOC6H4 | 54(84)b |
5 | H | Me | 3,4-(MeO)2C6H3 | 97 |
6 | H | Me | 4-FC6H4 | 91(81)a |
7 | H | Me | 3-FC6H4 | 70 |
8 | H | Me | 4-ClC6H4 | 96 |
9 | H | Me | 2-ClC6H4 | 63(86)b |
10 | H | Me | 4-BrC6H4 | 94(85)a |
11 | H | Me | 4-MeOOCC6H4 | 36(94)b |
12 | H | Me | 4-CF3C6H4 | 31(87)b |
13 | H | Me | 1-Naphthyl | 89 |
14 | H | Me | Me | 85(74)a |
15 | H | Me | nPr | 76 |
16 | H | Me | tBu | 58 |
17 | H | Me | Cyclohexyl | 73 |
18 | H | C6H5 | C6H5 | 74 |
19 | H | 4-MeC6H4 | C6H5 | 71 |
20 | H | 4-FC6H4 | C6H5 | 76 |
21 | H | 4-ClC6H4 | C6H5 | 73 |
22 | H | 4-BrC6H4 | C6H5 | 68 |
23 | H | 2,4,6-(Me)3C6H2 | C6H5 | 0 |
24 | 6-Cl | C6H5 | C6H5 | 73 |
25 | 6-Me | Me | C6H5 | 92 |
26 | 6-F | Me | C6H5 | 94(97)a |
27 | 7-Cl | Me | C6H5 | 91 |
28 | H | H | C6H5 | 53 |
29 | H | nBu | C6H5 | 56 |
30 | H | cPn | C6H5 | 71 |
31 | H | Hexadecyl | C6H5 | 68 |
The possible mechanism is depicted in Scheme 50. First of all, dehydrogenative oxidation of the alcohol (64) into the corresponding carbonyl compound (64′) promoted by ammonia, generates the gold-hydride species (b) and 76a′ is reduced into 76b in situ by b. This is the first hydrogen-transfer process and also the rate-limiting step of the reaction. Then, 76b can readily react with 64a′ to afford the corresponding imine (c). Compound c is converted to the intermediate (d) under the catalysis of gold. Subsequently, d can be rapidly oxidized to the product of 75 in the presence of the gold catalyst accompanied with the generation of b. And 76a′ is again reduced into 76b by b. This is the second hydrogen-transfer process. In the whole catalytic cycle, the alcohol 64 and the intermediate d are used as the reductant (hydrogen donor) once and the nitro compound 76a′ is used as the oxidant (hydrogen acceptor) twice.87
Entry | R | X | R1 | Product | Method | Yield (%) |
---|---|---|---|---|---|---|
1 | C6H5 | CN | C6H5 | 78a | A | 90 |
2 | 4-ClC6H4 | CN | C6H5 | 78b | A | 88 |
3 | C6H5 | CN | 4-ClC6H4 | 78c | A | 91 |
4 | 4-ClC6H4 | CN | 4-ClC6H4 | 78d | A | 91 |
5 | 4-O2NC6H4 | CN | 4-ClC6H4 | 78e | A | 90 |
6 | 4-O2NC6H4 | CN | 2,4-Cl2C6H4 | 78f | A | 86 |
7 | 4-O2NC6H4 | CN | 4-O2NC6H4 | 78g | A | 71 |
8 | C6H5 | CN | 4-MeOC6H4 | 78h | A | 84 |
9 | 4-O2NC6H4 | CN | 4-MeOC6H4 | 78i | A | 81 |
10 | C6H5 | CN | 4-tBuC6H4 | 78j | A | 80 |
11 | 4-O2NC6H4 | CN | 4-tBuC6H4 | 78k | A | 75 |
12 | 4-Cl-3O2NC6H3 | CN | C6H5 | 78l | A | 86 |
13 | 2,4,6-(MeO)3C6H2 | CN | C6H5 | 78m | A | 78 |
14 | 2,3-Cl2C6H4 | CN | C6H5 | 78n | A | 91 |
15 | C6H5 | CN | C6H5 | 78a | A | — |
16 | C6H5 | CN | C6H5 | 78a | B | 89 |
17 | 4-BrC6H4 | CN | C6H5 | 78o | B | 88 |
18 | 3-O2NC6H4 | CN | C6H5 | 78p | B | 91 |
19 | 4-ClC6H4 | CN | C6H5 | 78q | B | 86 |
20 | 3-BrC6H4 | CN | C6H5 | 78r | B | 81 |
21 | 2-BrC6H4 | CN | C6H5 | 78s | B | 87 |
22 | 4-MeC6H4 | CN | C6H5 | 78t | B | 90 |
23 | C6H5 | COOMe | C6H5 | 78u | B | 83 |
24 | 3-O2NC6H4 | COOMe | C6H5 | 78v | B | 84 |
25 | 4-ClC6H4 | COOMe | C6H5 | 78w | B | 85 |
26 | 4-O2NC6H4 | COOMe | C6H5 | 78x | B | 92 |
27 | 4-ClC6H4 | COOEt | C6H5 | 78y | B | 82 |
28 | 4-O2NC6H4 | COOEt | C6H5 | 78z | B | 86 |
29 | 4-MeC6H4 | COOEt | C6H5 | 78aa | B | 89 |
30 | Ferrocenyl | CN | C6H5 | 78ab | B | — |
31 | C6H5 | CN | C6H5 | 78a | C | 92 |
32 | 4-ClC6H4 | CN | C6H5 | 78b | C | 90 |
33 | 4-FC6H4 | CN | C6H5 | 78ac | C | 92 |
34 | 2-ClC6H4 | CN | C6H5 | 78ad | C | 88 |
35 | 3-ClC6H4 | CN | C6H5 | 78ae | C | 94 |
36 | 2-O2NC6H4 | CN | C6H5 | 78af | C | 88 |
37 | 4-O2NC6H4 | CN | C6H5 | 78ag | C | 89 |
38 | 2,4-Cl2C6H3 | CN | C6H5 | 78ah | C | 90 |
39 | 3-O2NC6H4 | CN | C6H5 | 78p | C | 90 |
40 | 4-MeC6H4 | CN | C6H5 | 78t | C | 89 |
41 | 3-BrC6H4 | CN | C6H5 | 78r | C | 93 |
42 | 2-BrC6H4 | CN | C6H5 | 78s | C | 92 |
43 | 4-BrC6H4 | CN | C6H5 | 78o | C | 89 |
44 | n-Heptanal | CN | C6H5 | 78ai | C | — |
Naeimi et al. also developed an efficient clean method for the synthesis of pyrazolo[1,2-a][1,2,4]triazole derivatives 75 via a one-pot three-component reaction of aromatic aldehydes 7, 77 and 46 in the presence of a catalytic amount of nanocrystalline (NC) magnesium oxide (Scheme 51, Table 41, Method B).89
Shaterian and Moradi used a similar approach for the synthesis of 7-amino-1,3-dioxo-1,2,3,5-tetrahydropyrazolo[1,2-a][1,2,4]triazole derivatives 78 by employing magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane (Fig. 22) as a catalyst for a similar reaction (Scheme 51, Table 41, Method C).90
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
1 | H | H | 79a | 56 |
2 | Me | Et | 79b | 67 |
3 | C6H5 | C6H5 | 79c | 71 |
4 | 4-MeOC6H4 | 4-MeOC6H4 | 79d | 70 |
5 | Me | Me | 79e | 67 |
6 | Et | Et | 79f | 70 |
Entry | R1 R2 | R3 | Yield (%) |
---|---|---|---|
1 | –(CH2)5 | C6H5 | 86 |
2 | –(CH2)2–O–(CH2)2– | C6H5 | 74 |
3 | Bu,Bu | C6H5 | 91 |
4 | Me,Bn | C6H5 | 80 |
5 | Bn,Bn | C6H5 | 93 |
6 | –(CH2)5 | 4-MeC6H4 | 69 |
7 | –(CH2)5 | 4-F3CC6H4 | 76 |
8 | –(CH2)5 | 4-MeOOCC6H4 | 59 |
9 | –(CH2)5 | 4-Me2NC6H4 | 93 |
10 | –(CH2)5 | 4-MeOC6H4 | 86 |
11 | –(CH2)5 | 4-BrC6H4 | 73 |
12 | Bn,Bn | 4-MeC6H4 | 91 |
13 | Bu,Bu | nDecyl | 64 |
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
a Methylphenylketone is used and the product is ![]() |
||||
1 | H | 4-MeOC6H4 | 82a | 85 |
2 | H | 3-MeOC6H4 | 82b | 84 |
3 | H | 2-MeOC6H4 | 82c | 69 |
4 | H | 4-MeC6H4 | 82d | 88 |
5 | H | 3-MeC6H4 | 82e | 82 |
6 | H | 2-MeC6H4 | 82f | 91 |
7 | H | 4-ClC6H4 | 82g | 92 |
8 | H | 3-ClC6H4 | 82h | 88 |
9 | H | 2-ClC6H4 | 82i | 70 |
10 | H | 4-BrC6H4 | 82j | 85 |
11 | H | 4-Me2NC6H4 | 82k | 72 |
12 | H | 4-F3CC6H4 | 82l | 65 |
13 | H | 3-F3CC6H4 | 82m | 86 |
14 | H | 2-F3C6H4 | 82n | 72 |
15 | H | 4-MeOOCC6H4 | 82o | 64 |
16 | H | 3-O2NC6H4 | 82p | 81 |
17 | H | 4-NCC6H4 | 82q | 90 |
18 | H | 2-Furyl | 82r | 78 |
19 | H | 2-Thienyl | 82s | 86 |
20 | H | 2-Pyridyl | 82t | 74 |
21 | H | 2-Thiazolyl | 82u | 71 |
22 | H | 2-Styryl | 82v | 78 |
23 | H | a | 82w | 84 |
24 | 3-Me | C6H5 | 82x | 83 |
25 | 4-Me | C6H5 | 82y | 80 |
26 | 4-Me | 4-BrC6H4 | 82z | 78 |
27 | 4-CF3 | C6H5 | 82aa | 75 |
28 | 3-Br-2-Me | C6H5 | 82ab | 61 |
29 | 2,4-Br2-6-Me | C6H5 | 82ac | 55 |
30 | 3-O2N | C6H5 | 82ad | — |
Guntreddi et al. demonstrated the catalytic use of magnetic nano-Fe3O4–KHSO4·SiO2 for an efficient one pot synthesis of imidazo[1,2-a]pyridines 83 by one pot three-component reaction of 2-aminopyridine 9, aldehyde 7, and alkyne 35 (Scheme 55, Table 45, Method A).94
Entry | R1 | R2 | Method | Product | Yield (%) |
---|---|---|---|---|---|
1 | H | C6H5 | A | 83a | 89 |
2 | H | 4-ClC6H4 | A | 83b | 86 |
3 | H | 3-ClC6H4 | A | 83c | 84 |
4 | H | 4-BrC6H4 | A | 83d | 83 |
5 | H | 3-BrC6H4 | A | 83e | 82 |
6 | H | 2-BrC6H4 | A | 83f | 83 |
7 | H | 4-MeOC6H4 | A | 83g | 75 |
8 | H | 4-Me2NC6H4 | A | 83h | — |
9 | H | 4-MeC6H4 | A | 83i | 79 |
10 | H | 4-O2NC6H4 | A | 83j | 69 |
11 | H | 2-O2NC6H4 | A | 83k | 65 |
12 | H | Et | A | 83l | 70 |
13 | H | 2-Furyl | A | 83m | 72 |
14 | H | 3-MeO-4-OHC6H4 | A | 83n | 55 |
15 | H | 4-ClC6H4 | B | 83b | 90 |
16 | H | C6H5 | B | 83b | 92 |
17 | H | 4-MeOC6H4 | B | 83g | 85 |
18 | H | 4-BrC6H4 | B | 83d | 90 |
19 | H | 4-MeC6H4 | B | 83i | 78 |
20 | H | 4-NCC6H4 | B | 83o | 95 |
21 | H | 4-F3CC6H4 | B | 83p | 90 |
22 | H | 4-FC6H4 | B | 83q | 95 |
23 | H | 2-MeC6H4 | B | 83r | 80 |
24 | H | 2-ClC6H4 | B | 83s | 87 |
25 | H | 3-BrC6H4 | B | 83e | 82 |
26 | H | 3-ClC6H4 | B | 83c | 85 |
27 | H | 1-Naphthyl | B | 83t | 78 |
28 | H | 2-Furyl | B | 83u | 90 |
29 | H | nPr | B | 83v | 65 |
30 | H | iPr | B | 83w | 76 |
31 | 3-Me | C6H5 | B | 83x | 82 |
32 | 3-Me | C6H5 | B | 83y | 78 |
Tajbakhsh et al. synthesized a magnetically recoverable nano-catalyst based on a biimidazole Cu(I) complex by covalent grafting of biimidazole on chloride-functionalized silica@magnetite nanoparticles, followed by metalation with CuI. The prepared nanocatalyst was also shown to have excellent and green catalytic activity in the synthesis of imidazo[1,2-a]pyridines 83a–y via the one-pot reaction of 2-aminopyridines 9, aldehydes 7 and phenylacetylene 35 in aqueous media (Scheme 55, Table 45, Method B).95
Multi-component reaction of various types of aldehydes 7, 2-aminopyridines 9 and trimethylsilyl cyanide was carried out in the presence of MCM-41 supported boron trifluoride (BF3/MCM-41) as a nanostructured solid acid catalyst for the synthesis of 3-iminoaryl-imidazo[1,2-a]pyridine derivatives 84a–i (Scheme 56, Table 46). MCM-41 nanoparticles were synthesized by a sol–gel method and BF3/MCM-41 samples with various loading amounts of BF3 and different calcination temperatures were prepared and characterized by XRD, SEM and FT-IR techniques.96
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
1 | H | H | 84a | 95 |
2 | H | 6-Me | 84b | 75 |
3 | 3-Pyridyl | H | 84c | 85 |
4 | 4-Me | H | 84d | 80 |
5 | 4-MeO | H | 84e | 80 |
6 | 4-F | H | 84f | 80 |
7 | 4-Me | 6-Me | 84g | 85 |
8 | 2-OH | 4-Me | 84h | 80 |
9 | 4-F | 6-Me | 84i | 75 |
Sanaeishoar et al. prepared LaMnO3 perovskit nanoparticles using a sol–gel method. This perovskite-type oxide as a green and reusable catalyst for the synthesis of imidazo[1,2-a]pyridines 85a–o by the reaction between 2-aminopyridine 9, benzaldehydes 7, and cyclohexyl isocyanide under solvent-free conditions within 1.5 h at 35 °C (Scheme 57, Table 47). The products 85a–o were prepared under solvent free conditions without any additives.97
Entry | X | R | Product | Yield (%) |
---|---|---|---|---|
1 | H | C6H5 | 85a | 96 |
2 | H | 4-MeC6H4 | 85b | 95 |
3 | H | 4-ClC6H4 | 85c | 99 |
4 | H | 4-Me2NC6H4 | 85d | 94 |
5 | H | 2-Fluorenyl | 85e | 95 |
6 | H | 4-MeOC6H4 | 85f | 91 |
7 | H | 4-BrC6H4 | 85g | 99 |
8 | H | 2-Thiophen | 85h | 97 |
9 | Me | C6H5 | 85i | 95 |
10 | Me | 4-MeC6H4 | 85j | 94 |
11 | Me | 2,4-Me2C6H3 | 85k | 91 |
12 | Me | 4-ClC6H4 | 85l | 98 |
13 | Me | 4-Me2NC6H4 | 85m | 94 |
14 | Me | 2-Fluorenyl | 85n | 94 |
15 | Me | 4-BrC6H4 | 85o | 99 |
Entry | R | R1 | Product | Yield% |
---|---|---|---|---|
1 | C6H5 | Me | 87a | 89 |
2 | 4-MeOC6H4 | Me | 87b | 92 |
3 | 4-FC6H4 | Me | 87c | 88 |
4 | 4-MeC6H4 | Me | 87d | 92 |
5 | C6H5 | H | 87e | 91 |
6 | 4-MeOC6H4 | H | 87f | 91 |
7 | 4-FC6H4 | H | 87g | 86 |
8 | 4-MeC6H4 | H | 87h | 88 |
9 | 2-Furyl | H | 87i | 78 |
The Fe3+ of the magnetic nanoparticles (CuFe2O4) has shown excellent catalytic activity in promoting the Knoevenagel condensation reaction by enhancing the electrophilicity of the aromatic aldehydes 7. The Cu2+ of CuFe2O4 catalyzes the subsequent Michael addition reaction of the 6-aminouracil 86 to the α,β-unsaturated nitroalkene.
Entry | X | R | Product | Yield (%) |
---|---|---|---|---|
1 | 4-Me | Me | 89a | 97 |
2 | 2,4-Cl2 | Me | 89b | 98 |
3 | 4-Br | Me | 89c | 90 |
4 | 4-PhCH2O | Me | 89d | 95 |
5 | 2,3-Cl2 | Me | 89e | 98 |
6 | 4-Cl | Me | 89f | 98 |
7 | 4-MeO | Me | 89g | 90 |
8 | 4-F | Me | 89h | 98 |
9 | 4-Me | Me | 89i | 98 |
10 | 4-CN | Me | 89j | 96 |
11 | 4-Cl | COMe | 89k | 90 |
12 | 4-PhCH2O | COMe | 89l | 90 |
13 | 4-CN | COMe | 89m | 95 |
14 | 2,3-Cl2 | H | 89n | 95 |
15 | 3-O2N | H | 89o | 96 |
16 | 2,4-Cl2 | H | 89p | 98 |
It is worth mentioning that 3,5-dibenzylidenepiperidin-4-one with electron-withdrawing groups on the phenyl rings induce greater electronic positive charge on the corresponding β-atoms and reacted rapidly whereas electron-rich groups on the phenyl rings require longer reaction times.
A plausible mechanism for the formation of pyrazolo[4,3-c]pyridines 89a–p is shown in Scheme 60. Because of the Lewis acidity property of the Fe3+, the intermediate 88 can be formed through the reaction of hydrazine hydrate with activated CC double bond of 3,5-dibenzylidenepiperidin-4-one 88. Then, the nucleophilic attack of the other NH2 group on the carbonyl (C
O) moiety gives intermediate (4). Finally, the expected product (5) is afforded by water elimination.
Entry | R1 | R2 | Product | Timea (min) | Yieldb (%) |
---|---|---|---|---|---|
a Time required for completion of the reaction as indicated by TLC.b Yield of isolated and purified products. | |||||
1 | Ph | Ph | 92a | 12 | 91 |
2 | Ph | Bn | 92b | 15 | 88 |
3 | Me | Ph | 92c | 12 | 90 |
4 | Me | Bn | 92d | 12 | 89 |
5 | 4-ClC6H4 | Ph | 92e | 14 | 94 |
6 | 4-ClC6H4 | Bn | 92f | 12 | 92 |
7 | Ph | Ph | 93a | 15 | 91 |
8 | Ph | Bn | 93b | 15 | 90 |
9 | Me | Ph | 93c | 15 | 90 |
10 | Me | Bn | 93d | 12 | 86 |
11 | 4-ClC6H4 | Ph | 93e | 13 | 92 |
12 | 4-ClC6H4 | Bn | 93f | 12 | 95 |
Entry | Ar | Product | Method | Time (min) | Yield (%) |
---|---|---|---|---|---|
1 | Ph | 95a | A | 11 | 89 |
2 | 4-FC6H4 | 95b | A | 5 | 95 |
3 | 4-ClC6H4 | 95c | A | 6 | 92 |
4 | 3-ClC6H4 | 95d | A | 8 | 88 |
5 | 4-BrC6H4 | 95e | A | 11 | 87 |
6 | 3-O2NC6H4 | 95f | A | 5 | 90 |
7 | 4-O2NC6H4 | 95g | A | 6 | 91 |
8 | 2,4-Cl2C6H3 | 95h | A | 11 | 88 |
9 | 3-EtO-4-HOC6H3 | 95i | A | 14 | 86 |
10 | 4-PhC6H4 | 95j | A | 9 | 91 |
11 | 2-Naphthyl | 95k | A | 11 | 90 |
12 | 4-HOCC6H4 | 95l | A | 10 | 86 |
13 | PhCH![]() |
95m | A | 80 | Trace |
14 | PhCH2CH2 | 95n | A | 80 | Trace |
15 | Ph | 95a | B | 15 | 97 |
16 | 4-MeOC6H4 | 95o | B | 30 | 83 |
17 | 4-MeC6H4 | 95p | B | 20 | 93 |
18 | 2-ClC6H4 | 95q | B | 30 | 86 |
19 | 3-ClC6H4 | 95d | B | 15 | 91 |
20 | 4-ClC6H4 | 95c | B | 15 | 95 |
21 | 4-BrC6H4 | 95e | B | 20 | 90 |
22 | 4-PhC6H4 | 95j | B | 15 | 90 |
23 | 4-OHCC6H4 | 95l | B | 10 | 83 |
24 | 3-O2NC6H4 | 95f | B | 10 | 98 |
25 | 4-O2NC6H4 | 95g | B | 10 | 97 |
26 | 2-FC6H4 | 95r | B | 10 | 90 |
27 | 2-Naphthyl | 95k | B | 12 | 92 |
28 | Ph | 95a | C | 15 | 96 |
29 | 4-MeOC6H4 | 95o | C | 25 | 85 |
30 | 4-MeC6H4 | 95p | C | 15 | 92 |
31 | 2-ClC6H4 | 95q | C | 20 | 88 |
32 | 3-ClC6H4 | 95d | C | 15 | 96 |
33 | 4-ClC6H4 | 95c | C | 10 | 95 |
34 | 4-BrC6H4 | 95e | C | 15 | 92 |
35 | 4-PhC6H4 | 95j | C | 15 | 87 |
36 | 4-OHCC6H4 | 95l | C | 10 | 87 |
37 | 3-O2NC6H4 | 95f | C | 10 | 97 |
38 | 4-O2NC6H4 | 95g | C | 5 | 97 |
39 | 2-FC6H4 | 95r | C | 5 | 91 |
Azarifar et al. reported also the synthesis of highly functionalized 1,4-dihydropyrano[2,3-c]pyrazole derivatives 95 from the ultrasound promoted reactions between 7, 45 and 94 in the presence of nano-titania-supported Preyssler-type heteropolyacid (n-TiO2/H14[NaP5W30O110]) as an efficient and reusable heterogeneous catalyst (Scheme 62, Table 51, Method B).69
Nano-titania sulfuric acid (15 nm TSA) was also used as an efficient and reusable heterogeneous catalyst to furnish the synthesis of 95 in high to excellent yields by a similar ultrasound promoted reactions (Scheme 62, Table 51, Method C).70
A four-component reaction of hydrazine hydrate or phenyl hydrazine 23, ethyl 3-alkyl-3-oxo propanoate 15, aldehydes 7 and malononitrile 46 has been performed in the presence of nanosized magnesium oxide as a highly effective heterogeneous base catalyst to produce of 6-amino-3-alkyl-4-aryl-5-cyano-1,4-dihydropyrano[2,3-c]pyrazole derivatives 96 in excellent yields and in a short experimental time. This method is simple and rapid for focusing a pyrano ring with a pyrazole ring (Scheme 63, Table 52, Method A).101
Entry | R | R1 | Ar | Product | Method | Yield (%) |
---|---|---|---|---|---|---|
1 | H | Me | C6H5 | 96a | A | 97 |
2 | H | Me | 2-ClC6H4 | 96b | A | 93 |
3 | H | Me | 4-ClC6H4 | 96c | A | 97 |
4 | H | Me | 3-BrC6H4 | 96d | A | 90 |
5 | H | Me | 4-O2NC6H4 | 96e | A | 90 |
6 | H | Me | 4-MeOC6H4 | 96f | A | 89 |
7 | Ph | Me | C6H5 | 96g | A | 95 |
8 | Ph | Me | 4-MeC6H4 | 96h | A | 93 |
9 | Ph | Me | 4-MeOC6H4 | 96i | A | 90 |
10 | Ph | Me | 4-ClC6H4 | 96j | A | 96 |
11 | Ph | Me | 2,4-Cl2C6H3 | 96k | A | 92 |
12 | Ph | Me | 4-BrC6H4 | 96l | A | 88 |
13 | Ph | Pr | 4-ClC6H4 | 96m | A | 92 |
14 | Ph | iPr | 4-ClC6H4 | 96n | A | 93 |
15 | Ph | iPr | 2,4-Cl2C6H3 | 96o | A | 95 |
16 | H | Me | C6H5 | 96a | B | 96 |
17 | H | Me | 3-MeO-4-HOC6H3 | 96p | B | 81 |
18 | H | Me | 4-ClC6H4 | 96j | B | 93 |
19 | H | Me | 4-MeOC6H4 | 96i | B | 89 |
20 | H | Me | 4-O2NC6H4 | 96e | B | 87 |
21 | H | Me | 2,4-Cl2C6H3 | 96k | B | 85 |
22 | H | Me | 4-BrC6H4 | 96l | B | 86 |
23 | H | Me | 3-BrC6H4 | 96d | B | 86 |
24 | H | Me | 2-ClC6H4 | 96b | B | 85 |
25 | H | Me | 2-O2NC6H4 | 96q | B | 82 |
26 | H | Me | 2,4-Cl2C6H3 | 96k | B | 87 |
27 | H | Me | 4-FC6H4 | 96r | B | 87 |
28 | H | Me | 4-MeC6H4 | 96h | B | 85 |
29 | H | Me | 2,5-(MeO)2C6H3 | 96s | B | 85 |
30 | H | Me | 3,4-(MeO)2C6H3 | 96t | B | 82 |
31 | H | Me | 3,4,5-(MeO)3C6H2 | 96u | B | 84 |
32 | H | Me | 4-HOC6H4 | 96v | B | 81 |
33 | H | Me | 4-Me2NC6H4 | 96w | B | 81 |
34 | H | Me | 3-O2NC6H4 | 96x | B | 92 |
Shaterian and Azizi et al. reported also a convenient and efficient solvent-free procedure for preparation of 6-amino-4-aryl-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 96 by a similar four component reaction in the presence of a catalytic amount of titanium dioxide nano-sized particles (Scheme 63, Table 52, Method B).102
Pradhan et al. synthesized CuFe2O4 magnetic nanoparticles and reported their use as an efficient catalyst for the one-pot synthesis of dihydropyrano[2,3-c]pyrazole derivatives 97a–k at mild conditions and in excellent yields. The four component reaction (4CRs) of a wide variety of substituted hydrazine derivatives 23, ethyl acetoacetate 15, dialkyl acetylenedicarboxylates 8 and alkyl nitrile derivatives 46 (malononitrile and ethyl cyanoacetate) gave the targeted dihydropyrano[2,3-c]pyrazoles 97a–k in good yield (Scheme 64, Table 53).72
Entry | R1 | R2 | R3 | Product | Yield (%) |
---|---|---|---|---|---|
1 | C6H5 | Et | CN | 97a | 95 |
2 | 4-O2NC6H4 | Et | CN | 97b | 90 |
3 | 4-BrC6H4 | Et | CN | 97c | 94 |
4 | 4-NCC6H4 | Et | CN | 97d | 94 |
5 | H | Et | CN | 97e | 97 |
6 | C6H5 | Me | COOEt | 97f | 93 |
7 | 4-O2NC6H4 | Me | COOEt | 97g | 98 |
8 | 4-BrC6H4 | Me | COOEt | 97h | 92 |
9 | 4-NCC6H4 | Me | COOEt | 97i | 92 |
10 | H | Me | COOEt | 97j | 96 |
11 | H | Et | COOEt | 97k | 85 |
Entry | R1 | R2 | R3 | Product | Time (h) | Yield (%) |
---|---|---|---|---|---|---|
1 | H | H | H | 100a | 5 | 91 |
2 | H | H | Me | 100b | 5 | 92 |
3 | H | 5-Cl | Me | 100c | 8 | 88 |
4 | H | 5-Br | H | 100d | 8 | 87 |
5 | H | 5-F | H | 100e | 5 | 90 |
6 | H | 5-F | Me | 100f | 5 | 93 |
7 | H | 5-Me | H | 100g | 7 | 87 |
8 | H | 5-Me | Me | 100h | 7 | 86 |
9 | Me | H | H | 100i | 6 | 90 |
10 | Me | H | Me | 100j | 6 | 92 |
11 | H | 5-O2N | H | 100k | 10 | Trace |
12 | H | 5-O2N | Me | 100l | 10 | Trace |
13 | H | 6-Cl | H | 100m | 7 | 91 |
14 | H | 6-Cl | Me | 100n | 8 | 88 |
15 | H | 6-Br | H | 100o | 7 | 88 |
16 | H | 6-Br | Me | 100p | 8 | 90 |
Entry | R | Product | Time (min) | Yield (%) | trans/cis Ratio |
---|---|---|---|---|---|
1 | Me | 103a | 10 | 89 | 98![]() ![]() |
2 | NH2 | 103b | 10 | 79 | 95![]() ![]() |
3 | H | 103c | 12 | 88 | 97![]() ![]() |
4 | Ph | 103d | 10 | 92 | 96![]() ![]() |
5 | 4-O2NC6H4 | 103e | 11 | 90 | 96![]() ![]() |
6 | 4-H2NC6H4 | 103f | 10 | 83 | 98![]() ![]() |
7 | Me | 105a | 11 | 86 | 96![]() ![]() |
8 | NH2 | 105b | 12 | 89 | 95![]() ![]() |
9 | H | 105c | 10 | 91 | 97![]() ![]() |
10 | Ph | 105d | 12 | 89 | 95![]() ![]() |
11 | 4-O2NC6H4 | 105e | 10 | 82 | 98![]() ![]() |
12 | 4-H2NC6H4 | 105f | 10 | 90 | 96![]() ![]() |
13 | Me | 103a | 4 | 45 | 95![]() ![]() |
14 | Me | 105a | 6 | 52 | 95![]() ![]() |
Entry | R | Product | Yield (%) |
---|---|---|---|
1 | C6H5 | 112a | 82 |
2 | C6H5 | 112b | 92 |
3 | 4-MeC6H4 | 112c | 84 |
4 | 4-CF3C6H4 | 112d | 79 |
5 | 4-MeOC6H4 | 112e | 84 |
6 | 4-BrC6H4 | 112f | 72 |
Entry | R | R1 | R2 | Product | Method | Yield (%) |
---|---|---|---|---|---|---|
a Product is the bis-derivative: ![]() |
||||||
1 | C6H5 | COMe | Me | 114a | A | 88 |
2 | 4-ClC6H4 | COMe | Me | 114b | A | 60 |
3 | 4-MeOC6H4 | COMe | Me | 114c | A | 81 |
4 | 4-O2NC6H4 | COMe | Me | 114d | A | 77 |
5 | 4-NCC6H4 | COMe | Me | 114e | A | 70 |
6 | 2-ClC6H4 | COMe | Me | 114f | A | 67 |
7 | C6H5 | CN | NH2 | 114g | B | 90 |
8 | 2-ClC6H4 | CN | NH2 | 114h | B | 89 |
9 | 3-ClC6H4 | CN | NH2 | 114i | B | 91 |
10 | 4-O2NC6H4 | CN | NH2 | 114j | B | 87 |
11 | 4-FC6H4 | CN | NH2 | 114k | B | 93 |
12 | 4-MeC6H4 | CN | NH2 | 114l | B | 86 |
13 | 2-BrC6H4 | CN | NH2 | 114m | B | 90 |
14 | 3-MeOC6H4 | CN | NH2 | 114n | B | 87 |
15 | 4-Pyridyl | CN | NH2 | 114o | B | 86 |
16 | 3-Pyridyl | CN | NH2 | 114p | B | 90 |
17 | 2-Naphthyl | CN | NH2 | 114q | B | 91 |
18 | 3-OHC-C6H4 | CN | NH2 | 114r | B | 88a |
19 | 2,4-Cl2C6H3 | CN | NH2 | 114s | B | 92 |
20 | 2,3-Cl2C6H3 | CN | NH2 | 114t | B | 91 |
21 | C6H5 | COMe | Me | 114a | C | 85 |
22 | 4-O2NC6H4 | COMe | Me | 114d | C | 88 |
23 | 4-NCC6H4 | COMe | Me | 114e | C | 87 |
24 | 4-ClC6H4 | COMe | Me | 114b | C | 84 |
The catalytic activity of nano-structured ZnO has also been explored in the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 114 via a three-component coupling reaction between 113, 15, and 7 (Scheme 71, Table 57, Method B).88 Almost all the reactions proceeded smoothly in relatively short reaction times (8–20 min) to afford the respective 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a–n in high yields (86–93%).
Kiasat and Davarpanah prepared Fe3O4@silica sulfuric acid core–shell nanocomposite (Fig. 23) and investigated its catalytic activity in the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives 114 (Scheme 71, Table 57, Method C). The attractive features of this method are simple procedure, cleaner reaction, use of reusable catalyst, easy workup and performing multicomponent reaction under solvent free conditions.107
Shaterian and Mohammadnia reported an efficient, one-pot procedure for preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives 116a–ab from four-component condensation reaction of hydrazine monohydrate 23, phthalic anhydride 115, malononitrile or ethyl cyanoacetate 46 and aromatic aldehydes 7 in the presence of magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane (Fig. 24) as catalyst under mild, ambient, and solvent-free conditions (Scheme 72, Table 58). The magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane can be recovered and reused several times without loss of activity.108
Entry | ArCHO | X | Product | Time (min) | Yield (%) |
---|---|---|---|---|---|
1 | C6H5CHO | CN | 116a | 19 | 92 |
2 | 2-ClC6H4CHO | CN | 116b | 15 | 93 |
3 | 3-ClC6H4CHO | CN | 116c | 16 | 90 |
4 | 4-ClC6H4CHO | CN | 116d | 15 | 93 |
5 | 4-FC6H4CHO | CN | 116e | 17 | 89 |
6 | 2-O2NC6H4CHO | CN | 116f | 14 | 91 |
7 | 4-BrC6H4CHO | CN | 116g | 15 | 92 |
8 | 3-BrC6H4CHO | CN | 116h | 16 | 89 |
9 | 3-ClC6H4CHO | CO2Et | 116i | 23 | 88 |
10 | 2-O2NC6H4CHO | CO2Et | 116j | 21 | 89 |
11 | 3-O2NC6H4CHO | CO2Et | 116k | 22 | 91 |
12 | 4-O2NC6H4CHO | CO2Et | 116l | 21 | 89 |
13 | 4-BrC6H4CHO | CO2Et | 116m | 22 | 90 |
14 | 2,6-Cl2C6H3CHO | CN | 116n | 14 | 92 |
15 | 2,4-Cl2C6H3CHO | CN | 116o | 15 | 91 |
16 | 2,3-Cl2C6H3CHO | CN | 116p | 16 | 93 |
17 | 2-MeOC6H4CHO | CN | 116q | 14 | 90 |
18 | 3-MeOC6H4CHO | CN | 116r | 16 | 92 |
19 | 2,4,6-(MeO)3C6H2CHO | CN | 116s | 17 | 91 |
20 | 2,6-(MeO)2C6H3CHO | CN | 116t | 16 | 93 |
21 | 5-MeC6H4CHO | CN | 116u | 16 | 92 |
22 | 4-F3CC6H4CHO | CN | 116v | 16 | 90 |
23 | 2,6-Cl2C6H3CHO | CO2Et | 116w | 22 | 89 |
24 | 2,4-Cl2C6H3CHO | CO2Et | 116x | 21 | 88 |
25 | 2,3-Cl2C6H3CHO | CO2Et | 116y | 23 | 89 |
26 | 2-MeOC6H4CHO | CO2Et | 116z | 22 | 90 |
27 | 4-F3CC6H4CHO | CO2Et | 116aa | 22 | 89 |
28 | n-Heptanal | CN | 116ab | 10 h | Trace |
Entry | R | Product | Yield (%) |
---|---|---|---|
1 | C6H5 | 118a | 87 |
2 | 4-MeO | 118b | 95 |
3 | 4-F | 118c | 85 |
4 | 4-Me | 118d | 87 |
5 | 3-O2N | 118e | 80 |
6 | 4-Cl | 118f | 85 |
7 | 3-HO-4-MeO | 118g | 84 |
8 | 4-O2N | 118h | 85 |
9 | 2,4-Cl2 | 118i | 90 |
10 | 4-Br | 118j | 87 |
11 | 2-Thienyl | 118k | 81 |
Entry | ArCHO | R | Time (min) | Product | Yield (%) |
---|---|---|---|---|---|
1 | C6H5CHO | Me | 13 | 119a | 88 |
2 | 2-O2NC6H4CHO | Me | 15 | 119b | 89 |
3 | 3-O2NC6H4CHO | Me | 10 | 119c | 89 |
4 | 4-O2NC6H4CHO | Me | 7 | 119d | 90 |
5 | 2-ClC6H4CHO | Me | 10 | 119e | 90 |
6 | 4-ClC6H4CHO | Me | 8 | 119f | 90 |
7 | 4-FC6H4CHO | Me | 10 | 119g | 88 |
8 | 4-MeC6H4CHO | Me | 12 | 119h | 87 |
9 | 2-MeOC6H4CHO | Me | 25 | 119i | 87 |
10 | 4-MeOC6H4CHO | Me | 28 | 119j | 85 |
11 | 3,4-(MeO)2C6H3CHO | Me | 36 | 119k | 86 |
12 | 4-NCC6H4CHO | Me | 14 | 119l | 85 |
13 | 4-HOC6H4CHO | Me | 35 | 119m | 86 |
14 | C6H5CHO | H | 12 | 119n | 90 |
15 | 4-BrC6H4CHO | H | 9 | 119o | 90 |
16 | 4-ClC6H4CHO | H | 8 | 119p | 91 |
17 | 4-MeOC6H4CHO | H | 30 | 119q | 86 |
18 | 4-NCC6H4CHO | H | 12 | 119r | 90 |
19 | 3-BrC6H4CHO | H | 8 | 119s | 87 |
20 | 3-MeOC6H4CHO | H | 30 | 119t | 88 |
Fekri et al. reported also an efficient, three component synthesis of novel class of decahydroacridine derivatives 120a–n from reaction between the appropriate aldehydes 7, dimedone 55 and ammonium acetate in the presence of nano Fe3O4 as a recyclable catalyst under ultrasonic irradiation (Scheme 74, Table 61, Method B).111
Entry | R | Method | Product | Yielda% |
---|---|---|---|---|
a Yield in methanol between paranthes. | ||||
1 | Ph | A | 125a | 86(96) |
2 | 4-MeOC6H4 | A | 125b | 85(95) |
3 | 3-O2NC6H4 | A | 125c | 92(96) |
4 | 4-O2NC6H4 | A | 125d | 93(97) |
5 | 4-ClC6H4 | A | 125e | 86(89) |
6 | 2-Furyl | A | 125f | 84(87) |
7 | 4-O2NC6H4 | B | 125g | 98 |
8 | Ph | B | 125a | 85 |
9 | 4-HOC6H4 | B | 125h | 85 |
10 | 4-MeOC6H4 | B | 125b | 50 |
11 | 4-ClC6H4 | B | 125e | 95 |
12 | 3-ClC6H4 | B | 125i | 75 |
13 | 2-ClC6H4 | B | 125j | 80 |
14 | 2-Thiophenyl | B | 125k | 90 |
15 | 2-Furyl | B | 125f | 60 |
Hosseini-Sarvari et al. used nano ZnO as an efficient catalyst for the synthesis of 2-amino-4H-chromenes 125a, 125b, 125e, 125f, 125g–k from methylenemalononitrile, generated in situ from aldehyde 7 and malononitrile 46 and naphthol 123 (Scheme 77, Table 62, Method B).84
Hosseini-Sarvari et al. also used nano ZnO to catalyze the reaction of various naphthalenediols 126, 128, 130, 132, 134 with aldehydes 7 and malononitrile 46 to produce 4H-benzo[h]chromene 127 and 129 (Scheme 78) and 1H-benzo[f]chromene 131, 133, and 135 (Scheme 79).84
Entry | R1 | R2 | Product | Yield (%) |
---|---|---|---|---|
1 | Et | CN | 137a | 90 |
2 | Et | CO2Et | 137b | 87 |
3 | Me | CN | 137c | 88 |
4 | Me | CO2Et | 137d | 84 |
Lashgari et al. applied sulfonic acid functionalized SBA-15 (SBA-Pr–SO3H) as a new nanoporous solid acid catalyst in the green one-pot three-component synthesis of spirooxindole-4H-pyrans 138a–i via condensation of isatins 58, malononitrile or methyl cyanoacetate or ethyl cyanoacetate 46, and 4-hydroxycoumarin 136 in water solvent (Scheme 81, Table 64).113
Entry | R | X | Product | Time (min) | Yield (%) |
---|---|---|---|---|---|
1 | H | CN | 138a | 15 | 90 |
2 | Cl | CN | 138b | 20 | 85 |
3 | Br | CN | 138c | 20 | 78 |
4 | H | CO2Me | 138d | 20 | 75 |
5 | Cl | CO2Me | 138e | 20 | 78 |
6 | Br | CO2Me | 138f | 35 | 75 |
7 | H | CO2Et | 138g | 30 | 83 |
8 | Cl | CO2Et | 138h | 30 | 91 |
9 | Br | CO2Et | 138i | 35 | 84 |
Entry | Ar | Product | Time (min) | Yield (%) |
---|---|---|---|---|
1 | Ph | 139a | 30 | 92 |
2 | 4-MeOC6H4 | 139b | 40 | 86 |
3 | 3-BrC6H4 | 139c | 35 | 90 |
4 | 4-O2NC6H4 | 139d | 25 | 92 |
5 | 3-O2NC6H4 | 139e | 30 | 90 |
6 | 2-ClC6H4 | 139f | 35 | 81 |
7 | 4-ClC6H4 | 139g | 25 | 92 |
8 | 4-FC6H4 | 139h | 30 | 89 |
9 | 2-Thiophene | 139i | 35 | 87 |
Entry | Ar | Product | Yield (%) |
---|---|---|---|
1 | 4-O2NC6H4 | 141a | 94 |
2 | 3-O2NC6H4 | 141b | 89 |
3 | 4-ClC6H4 | 141c | 91 |
4 | 2-ClC6H4 | 141d | 90 |
5 | 2,4-Cl2C6H3 | 141e | 96 |
6 | 4-HOC6H4 | 141f | 88 |
7 | 2-HOC6H4 | 141g | 85 |
8 | 4-MeC6H4 | 141h | 91 |
9 | 4-Me2NC6H4 | 141i | 94 |
10 | 2-Thienyl | 141j | 85 |
11 | 2-Furyl | 141k | 87 |
12 | 2-Pyridyl | 141l | 84 |
Entry | Ar | Product | Time (min) | Yield (%) |
---|---|---|---|---|
1 | 4-IC6H4 | 144a | 5 | 75 |
2 | 4-O2NC6H4 | 144b | 8 | 83 |
3 | 2-Me-4-O2NC6H4 | 144c | 8 | 75 |
4 | 2-ClC6H4 | 144d | 5 | 83 |
5 | 3-ClC6H4 | 144e | 5 | 95 |
6 | 4-ClC6H4 | 144f | 5 | 84 |
7 | Ph | 145a | 2 | 86 |
8 | 4-MeC6H4 | 145b | 1 | 79 |
9 | 4-MeOC6H4 | 145c | 1 | 87 |
Entry | R1 | R2 | Method | Product | Yield (%) |
---|---|---|---|---|---|
a The product was: ![]() |
|||||
1 | C6H5 | Me | A | 146a | 88 |
2 | 4-ClC6H4 | Me | A | 146b | 90 |
3 | 4-O2NC6H4 | Me | A | 146c | 94 |
4 | 4-HOC6H4 | Me | A | 146d | 85 |
5 | 4-NCC6H4 | Me | A | 146e | 92 |
6 | 3-FC6H4 | Me | A | 146f | 90 |
7 | 3-ClC6H4 | Me | A | 146g | 90 |
8 | 3-MeC6H4 | Me | A | 146h | 88 |
9 | 4-MeC6H4 | Me | A | 146i | 86 |
10 | 4-MeOC6H4 | Me | A | 146j | 85 |
11 | 2-O2NC6H4 | Me | A | 146k | 90 |
12 | C6H5 | Me | B | 146a | 93 |
13 | 2-MeC6H4 | Me | B | 146l | 91 |
14 | 4-MeC6H4 | Me | B | 146i | 90 |
15 | 3-MeOC6H4 | Me | B | 146h | 87 |
16 | 4-MeOC6H4 | Me | B | 146j | 89 |
17 | 3,4-(MeO)2C6H3 | Me | B | 146m | 88 |
18 | 3-BrC6H4 | Me | B | 146n | 85 |
19 | 2-ClC6H4 | Me | B | 146o | 87 |
20 | 4-ClC6H4 | Me | B | 146b | 93 |
21 | 2,4-(Cl)2C6H3 | Me | B | 146p | 91 |
22 | 4-FC6H4 | Me | B | 146q | 90 |
23 | 2-O2NC6H4 | Me | B | 146k | 82 |
24 | 3-O2NC6H4 | Me | B | 146r | 86 |
25 | 4-O2NC6H4 | Me | B | 146c | 83 |
26 | 2-Naphthyl | Me | B | 146s | 84 |
27 | C6H5 | H | B | 146t | 86 |
28 | 4-Me | H | B | 146u | 88 |
29 | 4-MeOC6H4 | H | B | 146v | 90 |
30 | 4-O2NC6H4 | H | B | 146w | 83 |
31 | 4-FC6H4 | H | B | 146x | 89 |
32 | 3-HOCC6H4 | Me | B | 146y | 80a |
33 | C6H5 | Me | C | 146a | 85 |
34 | 4-ClC6H4 | Me | C | 146b | 98 |
35 | 4-MeOC6H4 | Me | C | 146j | 94 |
36 | 4-O2NC6H4 | Me | C | 146c | 72 |
37 | 4-MeC6H4 | Me | C | 146i | 70 |
38 | 4-CC6H4 | Me | C | 146e | 89 |
39 | 4-F3CC6H4 | Me | C | 146z | 78 |
40 | 4-NO2NC6H4 | Me | C | 146c | 87 |
41 | 4-ClC6H4 | Me | C | 146b | 70 |
42 | 3-O2NC6H4 | Me | C | 146r | 83 |
43 | 4-BrC6H4 | Me | C | 146aa | 80 |
44 | 4-EtOC6H4 | Me | C | 146ab | 70 |
Kiasat and Davarpanah prepared Fe3O4@silica sulfuric acid core–shell nanocomposite and investigated its catalytic activity also in the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-trione derivatives 146 by a similar one-pot three component reaction (Scheme 86, Table 68, Method B).107
Rostami et al. also applied N-propylsulfamic acid supported onto magnetic Fe3O4 nanoparticles (MNPs-PSA) as an efficient and magnetically recoverable catalyst for the synthesis of 2H-Indazolo[2,1-b]phthalazine-1,6,11(13H)-trione 146 from a similar one-pot three-component reaction (Scheme 86, Table 68, Method C).116
The same authors have developed this synthetic method for the preparation of bis-2H-indazolo[2,1-b]phthalazine-trione 146 derivative in a 2:
1.1
:
2 molar ratio of phthalhydrazide to isophthaladehyde and dimedone (Table 68, entry 32).116
Entry | Ar | Product | Yield (%) |
---|---|---|---|
1 | 4-ClC6H4 | 153a | 88 |
2 | 4-BrC6H4 | 153b | 86 |
3 | 4-NCC6H4 | 153c | 90 |
4 | 4-FC6H4 | 153d | 87 |
5 | 2-ClC6H4 | 153e | 88 |
6 | 2-BrC6H4 | 153f | 88 |
7 | 4-MeC6H4 | 153g | 82 |
This review compiles the literatures on the application of nanomaterials in heterocyclic synthesis. The fused heterocycles mentioned in this review are arranged in an organized manner with respect to the type of heterocyclic systems.
In most of the reactions the spent catalyst can be easily separated from the reaction mixture. It can also be reused without noticeable change in its catalytic activity. Magnetic nanomaterials can be easily recovered by simple magnet, therefore it makes the catalyst more efficient.
We hope that this review will be useful not only for organic synthetic and organometallic chemists, but also for heterocyclic and natural product synthetic chemists.
This journal is © The Royal Society of Chemistry 2015 |