Synthesis and characterization of two novel biological-based nano organo solid acids with urea moiety and their catalytic applications in the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol), coumarin-3-carboxylic acid and cinnamic acid derivatives under mild and green conditions

Abstract

2-Carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as novel, mild and biological-based nano organocatalysts with urea moiety were designed, synthesized and fully characterized by FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry, elemental analysis, thermal gravimetric, derivative thermal gravimetric, X-ray diffraction patterns, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy and UV/Vis analysis. The catalytic applications of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid were studied in the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol), coumarin-3-carboxylic acid and cinnamic acid derivatives via the condensation reaction between several aromatic aldehydes and 1-phenyl-3-methylpyrazol-5-one (synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols)), the Knoevenagel condensation of Meldrum’s acid with salicylaldehyde derivatives (synthesis of coumarin-3-carboxylic acids) and the condensation of Meldrum’s acid with aromatic aldehydes (synthesis of cinnamic acids) under mild and solvent-free conditions. In the presented studies, some products were formed and reported for the first time. The described nano organo solid acids have potential in industry.

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Introduction

It is broadly known that there is a growing need for more ecologically sustainable approaches in fine chemical processes and the pharmaceutical industry, with focus on the design, synthesis and applications of catalysts because catalysis has a major role in pollution prevention. This extension well-known as ‘Green Chemistry’ or ‘sustainable development’ requires a shift from the common focus of method efficacy, where attention is mainly on product yield, to one that gives economic value, limits waste and avoids the use of toxic or dangerous materials.^1–3 The significant properties seen in water, due to its chemical and physical properties, are very beneficial for selectivity and reactivity that cannot be achieved in other organic solvents and make it an efficient solvent for many organic reactions, not just for biochemical procedures.^4,5 In the field of organic chemistry for example nucleoside, peptide or combinatorial synthesis, available amine protecting groups are frequently needed which are stable under a wide range of reaction conditions and are simply and selectively cleavable.⁶

The design, synthesis and use of high efficiency catalysts in synthetic organic procedures such as metal-free organic molecules (organocatalysts) have a high amount of attention from the scientific community as they have gradually improved approaches for the synthesis of more complex molecules.⁷ Organocatalysts have an important influence and advantage in the creation of pharmacological intermediates when compared with transition metal catalysts. One advantage of organocatalysts relates to their favorable surface to volume ratio which enhances the contact between reactants and catalyst support and in turn increases the catalytic activity.^8–10

Heterocycles are very common in organic and bioorganic chemistry both industrially and biologically. Among them, pyrazoles appear in a range of bio-active drugs in the pharmaceutical industry, as they are the main structure moiety of various biologically active compounds.¹¹ For instance, they represent analgesic, anti-pyretic, anti-anxiety and anti-inflammatory properties. 2,4-Dihydro-3H-pyrazol-3-one derivatives counting 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) have a wide spectrum of agreed biological activity, being applied as antidepressant,¹² gastric secretion stimulatory,¹³ anti-pyretic,¹⁴ anti-bacterial¹⁵ anti-inflammatory¹⁶ and anti-filarial agents.¹⁷ Furthermore, the analogous 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) are used as insecticides,¹⁸ pesticides,¹⁹ fungicides²⁰ and dyestuffs²¹ and as the chelating and extracting reagents for numerous metal ions.²¹

Coumarin derivatives have a wide range of uses in the perfume, pharmaceutical, and cosmetic industries.²² Various carboxycoumarins have been applied as triplet sensitizers^23,24 and fluorescent probes.^25,26 Coumarin-3-carboxylic acid derivatives are common starting materials for the synthesis of coumarins, which are identified natural products and have various biological activities.²⁷ Coumarin-3-carboxylic acids are usually synthesized via Knoevenagel condensation²⁸ of ortho-hydroxyaryl aldehydes with malonic acid,^28,29 cyanoacetic ester³⁰ and malonic ester.^29,31

In biological chemistry, cinnamic acid is a main intermediate in phenylpropanoid and shikimate methods. Shikimic acid is a precursor of aromatic amino acids, numerous alkaloids and indole derivatives. It is created both in free form, and in the form of esters (cinnamyl, ethyl, benzyl), in several essential oils, oil of cinnamon, resins and balsams, balsam of Peru and balsam of Tolu etc. These derivatives are significant intermediates in the biosynthetic process of most aromatic natural products. They are broadly spread in plants and have a broad range of activities.³² Furthermore cinnamic acids are also applied as precursors for the synthesis of commercially significant cinnamic esters.³³

In continuation of our previous studies related to the design, synthesis, applications and development of novel solid acids,³⁴ N-halo reagents,³⁵ novel nano structure, green and harmless ionic liquids, molten salts and organocatalysts for organic functional group transformations,³⁶ herein, we wish to report the synthesis and characterization of two biological-based nano organocatalysts with urea moiety. With this aim, semicarbazide hydrochloride and urea have been used for the synthesis of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid, respectively (Scheme 1). The synthesized organocatalysts were used for the synthesis of numerous 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives via the condensation reaction between several aromatic aldehydes and 1-phenyl-3-methylpyrazol-5-one under mild, green and solvent-free conditions (Scheme 2). Moreover, in additional work two organocatalysts were used in the synthesis of several coumarin-3-carboxylic acids via the Knoevenagel condensation of Meldrum’s acid with salicylaldehyde derivatives, and in the synthesis of cinnamic acids via the condensation of Meldrum’s acid with aromatic aldehydes under mild, green and solvent-free conditions (Scheme 3).

Scheme 1 The synthesis of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid.

Scheme 2 The synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives using 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano organocatalysts.

Scheme 3 The synthesis of coumarin-3-carboxylic acid and cinnamic acid derivatives using 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts.

Results and discussion

Characterization of 2-carbamoylhydrazine-1-sulfonic acid as a nano structure organocatalyst (i)

The structure of 2-carbamoylhydrazine-1-sulfonic acid used as a novel nano structure organocatalyst, was studied and characterized by FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry, CHN, TG, DTG, DTA, EDX, XRD, SEM, TEM, AFM and UV/Vis analysis.

The IR spectrum of the nano organocatalyst showed two peaks at 3430 cm⁻¹ and 3304 cm⁻¹ which can be related to the N–H stretching group on the semicarbazide moiety and the O–H stretching group on the –SO₃H, respectively. Furthermore, the two peaks at 1207 cm⁻¹ and 1172 cm⁻¹ are linked to the vibrational modes of O–SO₂ bonds. The absorption related to S=O bond vibration appeared at 1043 cm⁻¹. Also, the two peaks at 1686 cm⁻¹ and 1609 cm⁻¹ are correlated to the C=O stretching group on amide moiety, respectively (Fig. S1†).

Moreover, the ¹H NMR and ¹³C NMR spectra of the 2-carbamoylhydrazine-1-sulfonic acid in DMSO-d₆ are confirmed in Fig. S2 and S3,† respectively. Fig. S2† shows that the main peak in the ¹H NMR spectra of the nano organocatalyst is linked to two –NH groups which are detected at δ = 9.35 ppm. The peaks related to the –SO₃H group are found at 8.73 ppm and the peak correlated to the –NH₂ group on semicarbazide moiety appears at 6.59 ppm.

Also, the significant peak in the ¹³C NMR spectra of the nano structure organocatalyst is related to the amide group on the semicarbazide moiety which is detected at δ = 158.2 ppm (Fig. S3†).

The mass spectrum is also in accordance with the catalyst structure and displays a parent peak at 155 m/z (Fig. S4†). Also, the elemental analysis data (CHNS) confirms the presence of a water molecule.

Thermal gravimetric (TGA), derivative thermal gravimetric (DTG) and differential thermal analysis (DTA) of 2-carbamoylhydrazine-1-sulfonic acid were considered at 25 to 700 °C, with a temperature increase rate of 10 °C min⁻¹ under a nitrogen atmosphere. The results are shown in Fig. 1. The TG, DTG and DTA analysis of the nano structure organocatalyst displayed significance losses in one step, and decomposed after 367 °C.

Fig. 1 TG, DTG and DTA analysis of 2-carbamoylhydrazine-1-sulfonic acid.

Energy-dispersive X-ray spectroscopy (EDX) from the attained nano structure organocatalyst confirmed the presence of the expected elements in the structure of the organocatalyst, namely oxygen and sulfur (Fig. 2).

Fig. 2 EDX of 2-carbamoylhydrazine-1-sulfonic acid.

The size, shape and morphology of 2-carbamoylhydrazine-1-sulfonic acid were studied using X-ray diffraction (XRD) pattern, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM) analysis. The XRD pattern of the organocatalyst was considered in an area of 10–90° (Fig. 3). As revealed in Fig. 3, the XRD pattern displays diffraction lines of high crystalline nature at 2θ ≈ 16.50°, 20.30°, 21.20°, 23.40°, 25.50°, 26.60°, 27.80°, 28.90°, 31.20°, 36.90°, and 40.20°. The peak width (FWHM), size and inter planar distance from the XRD pattern of 2-carbamoylhydrazine-1-sulfonic acid were considered in the 16.50° to 36.90° range and the achieved results are summarized in Table 1. For instance, assignments for the highest diffraction line, 26.60°, presented an FWHM of 0.15 and a crystalline size for the catalyst of ca. 54.42 nm using the Scherrer equation [D = Kλ/(β cos θ)] (where D is the crystalline size, K is the shape factor, being analogous to 0.9, λ is the X-ray wavelength, β is the full width at half maximum of the diffraction peak, and θ is the Bragg diffraction angle in degrees). An inter planar distance of 0.334710 nm (using the highest diffraction line at 26.60°) was found using the Bragg equation: dhkl = λ/(2 sin θ), (λ: Cu radiation, 0.154178 nm). Crystallite sizes obtained from several diffraction lines by the Scherrer equation were found to be in the nanometer range (27.02–54.42 nm), which is mainly in accordance with the SEM and TEM (Fig. 4).

Fig. 3 XRD pattern of 2-carbamoylhydrazine-1-sulfonic acid.

Table 1 XRD data for the 2-carbamoylhydrazine-1-sulfonic acid

Entry	2θ	Peak width [FWHM] (°)	Size (nm)	Inter planar distance (nm)
1	16.50	0.18	44.60	0.536612
2	20.30	0.17	47.47	0.436939
3	21.20	0.19	42.55	0.418590
4	23.40	0.22	36.88	0.379709
5	25.50	0.15	54.30	0.348895
6	26.60	0.15	54.42	0.334710
7	27.80	0.16	51.16	0.320529
8	28.90	0.20	41.02	0.308574
9	31.20	0.19	43.42	0.286331
10	36.90	0.31	27.02	0.243304
11	40.20	0.25	33.84	0.224059

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Fig. 4 SEM (a) and TEM (b, c and d) of 2-carbamoylhydrazine-1-sulfonic acid.

Atomic force microscopy (AFM) is a technique that lets us find and analyze surfaces with high resolution and attention. AFM provides great benefits, almost any model can be imaged: for example hard surfaces such as the surface of a ceramic material, or the dispersal of a metallic nano composite; or very soft, such as plastic materials, or molecules of proteins. Fig. 5 shows the two and three dimensional AFM images of 2-carbamoylhydrazine-1-sulfonic acid. No key division area in size is identified in the illustrations. From the three dimensional 2.1 μm² × 2.1 μm² framework, we can see that the achieved nano structure organocatalyst shows an interrupted structure with a preferable outside planarity. The surface of the coat on the 2-carbamoylhydrazine-1-sulfonic acid nano structure was clearly shown to be less than 65 nm.

Fig. 5 Two-dimensional (a and b) and three-dimensional (c and d) AFM topography images of 2-carbamoylhydrazine-1-sulfonic acid.

The UV/Vis absorbance spectrum of the nano structure organocatalyst was compared with those of reactants and reaction mixture to highlight the distinction between the UV/Vis absorbance pattern of the catalyst, reactants and reaction mixture. As revealed in Fig. S5,† λ_max in the UV/Vis spectrum of the organocatalyst was at about 227 nm. In the UV/Vis spectra of 4-chlorobenzaldehyde, 1-phenyl-3-methylpyrazol-5-one and the reaction mixture, the λ_max values displayed at about 252, 240 and 244 nm, respectively.

Characterization of carbamoylsulfamic acid as a nano structure organocatalyst (ii)

The structure of carbamoylsulfamic acid was considered and identified by FT-IR, ¹H NMR, ¹³C NMR, mass, CHN, TG, DTG, DTA, EDX, XRD, SEM, TEM and UV/Vis analysis.

The IR spectrum of the carbamoylsulfamic acid nano structure has two distinct peaks at 3331 cm⁻¹ and 3180 cm⁻¹ which can be assigned to the N–H stretching group on the urea moiety and O–H stretching group on –SO₃H, respectively. Additionally, the two peaks at 1233 cm⁻¹ and 1171 cm⁻¹ are related to vibrational modes of O–SO₂ bonds. The absorption correlated to S=O bond vibration appears at 1024 cm⁻¹. Moreover, the two peaks at 1700 cm⁻¹ and 1554 cm⁻¹ are correlated to the C=O stretching group and C–N stretching group on the amide moiety (Fig. S6†).

Furthermore, the ¹H NMR and ¹³C NMR spectra of the carbamoylsulfamic acid in DMSO-d₆ are shown in Fig. S7 and S8,† respectively. Fig. S7† displays a key peak related to –NH and –NH₂ group which are known at δ = 9.09 ppm, and peaks correlated to –SO₃H group are presented at 7.11 ppm.

Furthermore, the main peak of the ¹³C NMR spectra is linked to the amide group on the urea moiety which is identified at δ = 154.8 ppm (Fig. S8†).

The mass spectrum of the nano structure is in agreement with the structure of the catalyst and shows the parent peak at 140 m/z (Fig. S9†). Also, the elemental analysis data (CHNS) confirms the presence of a water molecule.

TGA, DTG and DTA of carbamoylsulfamic acid were also considered. The correlating diagrams are presented in Fig. 6. These reveal that the nano structure has good stability; accordingly there was no clear mass loss before 498 °C. The significant weight loss of the catalyst occurred after 498 °C, so it is suitable for catalytic applications in organic synthesis.

Fig. 6 TGA, DTG and DTA analysis of carbamoylsulfamic acid.

Energy-dispersive X-ray spectroscopy (EDX) from the achieved nano structure shows the existence of the anticipated elements in the structure, namely oxygen and sulfur (Fig. 7).

Fig. 7 EDX of carbamoylsulfamic acid.

To confirm the nano structure of carbamoylsulfamic acid, firstly, its XRD pattern was considered. As revealed in Fig. 8, the XRD pattern displays peaks at 2θ ≈ 15.70°, 21.50°, 23.20°, 24.70°, 30.10°, 34.10° and 41.80°. SEM and TEM were also carried out (Fig. 9). Peak width (FWHM), size and inter planar distance linked to the XRD pattern were considered in the 16.00° to 32.40° range and the achieved results are summarized in Table 2. The average crystallite size, D, was calculated by the Debye–Scherrer formula: D = Kλ/(β cos θ), K is the Scherrer constant, λ is the X-ray wavelength, β is the half-maximum peak width, and θ is the Bragg diffraction angle. The average size of the nano structure attained from this equation was found to be about 9.01–63.92 nm, which is in good agreement with the SEM and TEM images (Fig. 9).

Fig. 8 XRD pattern of the carbamoylsulfamic acid.

Fig. 9 SEM (a) and TEM (b, c and d) of carbamoylsulfamic acid.

Table 2 XRD data for the carbamoylsulfamic acid

Entry	2θ	Peak width [FWHM] (°)	Size (nm)	Inter planar distance (nm)
1	15.70	0.32	36.45	0.563772
2	21.50	0.63	12.84	0.414817
3	23.20	0.90	9.01	0.390921
4	24.70	0.25	32.53	0.360010
5	30.10	0.30	27.71	0.296539
6	34.10	0.13	63.92	0.262614
7	41.80	0.40	21.26	0.215845

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The UV/Vis absorbance spectrum of the nano structure was compared with that of the reactants, reaction mixture and product to highlight the difference. As displayed in Fig. S10,† λ_max in the UV/Vis spectrum of the organocatalyst appears at about 233 nm. In comparison the UV/Vis spectra of 4-chlorobenzaldehyde, 1-phenyl-3-methylpyrazol-5-one, the reaction mixture and product, have λ_max values presented at about 252, 240, 229 and 245 nm, respectively.

Application of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as nano structure organocatalysts in the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives

At first, to optimize the reaction conditions, the condensation reaction of 4-chlorobenzaldehyde and 1-phenyl-3-methylpyrazol-5-one was chosen as a model and various amounts of nano organocatalyst at 50–90 °C were confirmed on it under solvent-free conditions (Table 3). As revealed in Table 3, the best results were achieved when the reaction was attained in the presence of 10 mol% of organocatalyst at 60 °C (Table 3, entry 3). No improvement was observed in the yield with increasing the amount of the nano organocatalysts and temperature (Table 3, entries 4–12). Table 3 obviously shows that in the absence of a nano organocatalyst, the product formed in low yields. To compare the effect of the solution in comparison with solvent-free conditions, a mixture of 4-chlorobenzaldehyde and 1-phenyl-3-methylpyrazol-5-one was again used as a model. The presence of 10 mol% of nano organocatalysts in several solvents such as C₂H₅OH, CH₃CN, CH₃CO₂Et and toluene were studied at 60 °C. Solvent-free conditions were found to be the best.

Table 3 Results of the amount of catalyst and temperature on the condensation reaction of 4-chlorobenzaldehyde and 1-phenyl-3-methylpyrazol-5-one under solvent-free conditions

Entry	Catalyst amount (mol%)	Reaction temperature (°C)	Reaction time (min)		Yield (%)
			Cat (ii)	Cat (i)	Cat (ii)	Cat (i)
1	—	60	160	160	60	60
2	10	50	25	30	87	85
3	10	60	15	20	91	93
4	10	70	20	20	90	90
5	10	80	20	20	92	90
6	10	90	20	20	92	90
7	15	50	25	30	87	85
8	20	50	25	30	87	85
9	15	60	15	20	91	93
10	20	60	15	20	91	93
11	15	70	20	20	90	90
12	20	70	20	20	90	90

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After optimization of the reaction conditions, to study the efficacy and the scope of the offered process, several 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives were produced via the condensation reaction between aromatic aldehydes and 1-phenyl-3-methylpyrazol-5-one in the presence of catalytic amounts of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts under solvent-free reaction conditions. The results are presented in Table 4. The effect of substituents on the aromatic ring was estimated to have a strong effect in terms of yields under these reaction conditions. Both class of aromatic aldehydes with electron-releasing or electron-withdrawing substituents on their aromatic ring offered the favorable products in high to excellent yields within a short reaction time. The reaction times of aromatic aldehydes with electron withdrawing groups were faster than those with electron donating groups.

Table 4 Synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives using 10 mol% of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalyst

Entry	Aldehyde	Time (min)		Yield (%)		Mp (°C) [lit.]
		Cat (ii)	Cat (i)	Cat (ii)	Cat (i)
1	N,N-Dimethylaminobenzaldehyde	210	210	87	85	172–173
2	4-Chloro-3-nitrobenzaldehyde	20	20	95	92	238–240 [237–238]^37
3	3-Bromobenzaldehyde	15	12	96	98	172–174 [173–176]^38
4	Terephthalaldehyde (2 : 1)	30	25	90	87	211–213
5	Terephthalaldehyde	40	40	83	85	213–215 [194–196]^39
6	Terephthalaldehyde-mono-diethylacetal	60	50	89	85	254–255
7	3-Fluorobenzaldehyde	30	25	97	96	183–184
8	Ethyl-3-formyl-1H-indol-2-carbaldehyde	30	30	90	93	231–233
9	4-Pyridinecarboxaldehyde	20	20	94	93	248–250
10	4-Chlorobenzaldehyde	15	20	91	93	213–214 [215–216]^37
11	2-Chlorobenzaldehyde	12	15	95	94	236–237 [235–237]^37
12	2,4-Dichlorobenzaldehyde	25	30	90	85	229–230 [227–229]^37
13	3-Chlorobenzaldehyde	15	15	92	94	235–237 [150–152]^39
14	2-Methoxybenzaldehyde	40	45	88	90	212–213 [210–213]^37
15	3-Hydroxybenzaldehyde	30	30	93	94	166–168 [165–168]^40
16	Benzaldeyhe	20	20	95	93	161–163 [169–171]^37
17	3-Nitrobenzaldehyde	15	20	97	94	150–151 [151–154]^37
18	4-Nitrobenzaldehyde	10	10	98	95	230–232 [225]^37
19	3-Phenoxybenzaldehyde	25	30	94	97	194–195
20	α-Methylcinnamaldehyde	45	55	90	92	163–164
21	2-Hydroxybenzaldehyde	30	30	93	90	227–228 [227–229]^41
22	Naphthalene-2-carbaldehyde	27	35	95	90	206–207 [204–206]^37
23	Naphthalene-1-carbaldehyde	45	45	98	99	213–215 [228–230]^38
24	4-Hydroxy-3-methoxybenzaldehyde	45	50	91	94	205–207 [200–201]^42
25	2-Nitrobenzaldehyde	30	30	90	92	222–224 [221–223]^39
26	4-Bromobenzaldehyde	10	10	96	94	202–204 [183–185]^37
27	4-Fluorobenzaldehyde	20	25	95	97	145–146 [182–184]^37

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A probable mechanism to explain the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives 3, includes: an initial step to create benzylidene intermediate 8 via the nucleophilic addition of 1-phenyl-3-methyl-5-pyrazolone 2 to aromatic aldehyde 1 followed by dehydration; then, Michael addition after the 1-phenyl-3-methyl-5-pyrazolone 2 is added gives 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives 3 (Scheme 4).

Scheme 4 Suggested mechanism for the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives using 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts.

Additionally, reusability of the catalysts was examined upon condensation between 4-chlorobenzaldehyde and 1-phenyl-3-methylpyrazol-5-one. After the completion of the reaction, ethyl acetate was added to the reaction mixture and stirred and heated to separate the product and remaining starting materials from the catalyst. This solution was washed with absolute ethanol to separate the organocatalysts (the product and starting materials are soluble in hot ethyl acetate and the nano organocatalysts are soluble in absolute ethanol). The organocatalysts were then separated from the ethanol and reused for alternative reactions. The catalytic activity of the catalysts was retained within the limits of the experimental errors for four continuous runs (Fig. 10). The structure of the reused organocatalysts was confirmed via IR spectra. Furthermore, the size and morphology of the reused catalysts was studied by XRD (Fig. S11 and S12†).

Fig. 10 The reusability of the nano structure organocatalyst (i) in 20 minutes and nano structure organocatalyst (ii) in 15 minutes.

To study the efficacy of our organocatalysts (via the calculated TOF, TON and atomic economic values) on the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives, the condensation of 4-chlorobenzaldehyde and 1-phenyl-3-methylpyrazol-5-one was used as a model. The TOF values were calculated via the equation TOF = yield (%)/[time (min) × catalyst amount (mol%)]. TON values were calculated via the equation TOF = yield (%)/catalyst amount (mol%). Atomic economic values were calculated via the equation AE = [molecular weight/the total molecular weight] × 100. In the presence of cat (i) the TOF value was found to be 0.47, and using cat (ii) the TOF value 0.61 was found. In the presence of cat (i) the TON value 9.3 was measured, and using cat (ii) the TON was 9.1. In the presence of cat (i) or cat (ii) the atomic economic value, 96.32, was found (Table 5). In homogeneous catalyst systems, TON is the number of molecules of reactants that per molecule of catalyst converts to molecules of product. While, TOF is the number of molecules of reactants that molecule of catalyst can in seconds, minutes or hours converts them to molecules of product.

Table 5 TOF and TON of nano organocatalysts after recycling

Recycle	TOF		TON
	Cat (ii)	Cat (i)	Cat (ii)	Cat (i)
1	0.61	0.47	9.1	9.3
2	0.59	0.43	8.8	8.5
3	0.53	0.30	8.0	6.0
4	0.49	0.26	7.3	5.1

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Application of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as nano structure organocatalysts in the synthesis of coumarin-3-carboxylic acid

Initially, to optimize the reaction conditions, the condensation reaction of salicylaldehyde with Meldrum’s acid was selected as a model and different amounts of nano organocatalysts under 25–70 °C were confirmed under solvent-free conditions (Table 6). As shown in Table 6, the best results were attained when the reaction was carried out using 10 mol% of nano structure organocatalyst at 50 °C (Table 6, entry 3). No improvement in the yield was detected by further increasing the amount of nano organocatalyst or temperature (Table 6, entries 4–7). Table 6 clearly shows that using nano organocatalysts, product was synthesized in low yields. To compare the effect of solution or solvent-free conditions, the model reaction was run in the presence of 10 mol% of organocatalyst at 50 °C, in various solvents for example C₂H₅OH, CH₃CN, CH₃CO₂Et and toluene. Solvent-free conditions were the best for this reaction.

Table 6 The effect of catalyst and temperature on the condensation reaction between salicylaldehyde and Meldrum’s acid under solvent-free conditions

Entry	Catalyst amount (mol%)	Reaction temperature (°C)	Reaction time (min)		Yield (%)
			Cat (ii)	Cat (i)	Cat (ii)	Cat (i)
1	5	50	20	30	91	94
2	10	r.t.	180	180	70	72
3	10	50	5	15	97	98
4	10	60	5	15	97	98
5	10	70	5	15	97	98
6	15	50	5	15	96	96
7	20	50	5	15	96	96

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Following optimization, to study the efficiency and the scope of the introduced procedure, coumarin-3-carboxylic acid derivatives were formed via the Knoevenagel condensation reaction between several salicylaldehyde with Meldrum’s acid, using catalytic amounts of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the organocatalysts under solvent-free reaction conditions. The results are presented in Table 7. The effect of substituents on the aromatic ring was evaluated and has a strong effect in terms of yield. Aromatic salicylaldehydes with electron-releasing or electron-withdrawing substituents on their aromatic ring produced the appropriate products in high to excellent yields in a short reaction time. The reaction times of aromatic salicylaldehydes with electron withdrawing groups were faster than those with electron donating groups. In addition, reusability of the catalysts were also examined.

Table 7 Synthesis of coumarin-3-carboxylic acid derivatives via the Knoevenagel condensation using 10 mol% of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts

Entry	Salicylaldehyde	Time (min)		Yield (%)		Mp (°C)
		Cat (ii)	Cat (i)	Cat (ii)	Cat (i)
1	Salicylaldehyde	5	15	87	98	190–192 (ref. 43)
2	5-Bromosalicylaldehyde	20	30	94	95	196–198 (ref. 43)
3	2-Hydroxy-1-naphthaldehyde	40	50	95	96	183–185 (ref. 43)
4	5-Nitrosalicylaldehyde	15	20	97	85	216–217 (ref. 43)
5	5-Hydroxysalicylaldehyde	5	15	96	88	268–270 (ref. 44)
6	3-Hydroxysalicylaldehyde	40	30	95	83	284–286
7	3,5-Dichlorosalicylaldehyde	20	25	94	96	193–195 (ref. 44)

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Application of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts in the synthesis of cinnamic acid

To optimize the reaction conditions, the condensation reaction between benzaldehydes with Meldrum’s acid was selected as a typical reaction, and various amounts of nano organocatalyst at 25–110 °C were tested under solvent-free conditions (Table 8). As revealed in Table 8, the appropriate results were achieved when the reaction was carried out using 10 mol% of organocatalyst at 110 °C (Table 8, entry 6). No improvement was identified in the yield through increasing the amount of the nano organocatalyst or the temperature (Table 8, entries 7 and 8). Table 8 shows that in the presence of nano organocatalyst the product was produced in low yields. To compare the effect of the solution in comparison with solvent-free conditions, the model reaction was carried out using 10 mol% of organocatalyst at 110 °C, in various solvents such as C₂H₅OH, CH₃CN, CH₃CO₂Et and toluene. Solvent-free conditions were found to be best.

Table 8 Effect of the amount of catalyst and the temperature on the condensation reaction of benzaldehyde and Meldrum’s acid under solvent-free conditions

Entry	Catalyst amount (mol%)	Reaction temperature (°C)	Reaction time (min)			Yield (%)
			Cat (ii)	Cat (i)	Cat (ii)		Cat (i)
1	5	110	45	60	91		93
2	10	r.t.	180	180	50		50
3	10	60	180	180	75		75
4	10	90	120	120	96		94
5	10	100	60	60	95		96
6	10	110	20	25	97		98
7	15	110	20	25	96		97
8	20	110	20	25	95		92

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After optimization of the reaction conditions, to study the performance and the scope of the presented process, several cinnamic acid derivatives were synthesized via the condensation reaction between various aromatic aldehydes with Meldrum’s acid in the presence of catalytic amounts of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the organocatalysts under solvent-free reaction conditions. The results are shown in Table 9. The effect of aromatic ring substituents was estimated to have a strong effect on yield under these reaction conditions. Both class of aromatic aldehydes containing electron-releasing or electron-withdrawing substituents provided the applicable products in high to excellent yields in a short reaction time. The reaction times of aromatic aldehydes with electron withdrawing groups were faster than those with electron donating groups. Moreover, reusability of the catalysts were also studied.

Table 9 Synthesis of cinnamic acid derivatives using 10 mol% of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts

Entry	Aldehyde	Time (min)		Yield (%)		Mp (°C)
		Cat (ii)	Cat (i)	Cat (ii)	Cat (i)
1	Benzaldehyde	20	25	97	98	128–129 (ref. 45)
2	4-Chlorobenzaldehyde	5	10	94	94	254–256 (ref. 45)
3	2-Chlorobenzaldehyde	10	20	95	96	209–210
4	2,4-Dichlorobenzaldehyde	5	8	98	98	235–238
5	4-Nitrobenzaldehyde	5	10	93	95	292 ^46 ^(Decompose)
6	4-Chloro-3-nitrobenzaldehyde	15	20	95	93	187–189
7	3-Nitrobenzaldehyde	10	15	92	92	202–203 (ref. 45)
8	Naphthalene-1-carbaldehyde	5	8	96	95	215–217
9	3-Bromobenzaldehyde	10	12	94	93	174–175
10	4-Methoxybenzaldehyde	20	25	93	96	168–170 (ref. 45)
11	2-Methoxybenzaldehyde	30	40	91	94	183–185 (ref. 47)
12	4-Methylbenzaldehyde	30	30	95	94	200–202 (ref. 46)
13	Terephthalaldehyde	10	10	90	89	187^(Decompose)

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A probable mechanism for the synthesis of coumarin-3-carboxylic acids and cinnamic acids are suggested in Scheme 5.^43,45 The mechanism involves a Knoevenagel reaction between salicylaldehyde derivatives (4) with Meldrum’s acid (5) in the presence of catalytic amounts of 2-carbamoylhydrazine-1-sulfonic acid or carbamoylsulfamic acid to give adduct (17), followed by nucleophilic attack of the phenolic group on the carbonyl group of Meldrum’s acid. This resulted in the opening of Meldrum’s acid ring and the preparation of coumarin-3-carboxylic acid derivatives (6). Also, Meldrum’s acid has pK_a = 5 and because it is sensitive to heat, decyclization happens at high temperatures according to the previously proposed mechanism.⁴⁸ The initial step contains the formation of intermediate (21) via the nucleophilic addition of Meldrum’s acid with open ring (20) to aromatic aldehyde (8). Finally, the removal of one water molecule leads to the synthesis of cinnamic acids (7).

Scheme 5 Proposed mechanism for the synthesis of coumarin-3-carboxylic acids and cinnamic acids using 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as the nano structure organocatalysts.

To compare the efficacy of our catalyst with some reported catalysts for the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol), coumarin-3-carboxylic acid and cinnamic acid derivatives, we have presented the results of these catalysts in condensation reactions of: 4-nitrobenzaldehyde with 1-phenyl-3-methyl-5-pyrazolone (in the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol)); Meldrum’s acid with salicylaldehyde (in the synthesis of coumarin-3-carboxylic acid); and benzaldehyde with Meldrum’s acid (in the synthesis of cinnamic acid) in Table 10. As Table 10 shows, nano structure organocatalysts have remarkably improved the synthesis of products.

Table 10 Comparison of syntheses using the nano organocatalysts with those previously reported

Entry	Reaction condition	Catalyst loading	Time (min)	Yield (%)	Ref.
1	Cat (i), solvent-free, 60 °C	10 mol%	20	93	This work
2	Cat (ii), solvent-free, 60 °C	10 mol%	15	91	This work
3	[Dsim]AlCl4, solvent-free, 90 °C	1 mol%	40	91	36e
4	Silica-bonded S-sulfonic acid (SBSSA), EtOH, reflux condition	18 mol%	40	90	40
5	PEG-400, 110 °C	282 mol%	60	94	49
6	Poly(ethylene glycol)-bound sulfonic acid (PEG-SO3H), water, reflux condition	1.5 mol%	15	93	39
7	Cat (i), solvent-free, 50 °C	10 mol%	15	95	This work
8	Cat (ii), solvent-free, 50 °C	10 mol%	5	87	This work
9	Silica sulfuric acid, 120	0.02 g	45	90	50
10	SnCl2·2H2O, solvent-free, 80 °C	10 mol%	60	80	43
11	K3PO4, C2H5OH, r.t.	20 mol%	45	94	44
12	Cat (i), solvent-free, 110 °C	10 mol%	25	98	This work
13	Cat (ii), solvent-free, 110 °C	10 mol%	20	97	This work
14	Piperidine, C2H5OH (200 mL), 100 °C	1.5 mmol	7 h	80	51
15	BBr3, 4-DMAP, Py	—	12 h	65	45

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Conclusion

In summary, two novel, mild, green and efficient nano structure organo solid acids, 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid, with urea as a biological moiety were designed, synthesized and completely identified by FT-IR, ¹H NMR, ¹³C NMR, mass, elemental analysis, TG, DTG, XRD, SEM, TEM, EDX, AFM and UV/Vis analysis. The catalytic applications of the described organo solid acids were investigated for the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol), coumarin-3-carboxylic acid and cinnamic acid derivatives via the condensation reaction between several aromatic aldehydes and: 1-phenyl-3-methylpyrazol-5-one (synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols)); the Knoevenagel condensation of Meldrum’s acid with salicylaldehyde derivatives (synthesis of coumarin-3-carboxylic acids) and; the condensation of Meldrum’s acid with aromatic aldehydes (synthesis of cinnamic acids) under mild, green and solvent-free conditions. Further studies showed that the nano structure organocatalyst acidity plays a major role in the dual-catalyzed reactions. Significant advantages of these reactions are that they are relatively environmentally benign, biological-based, low cost, have a cleaner reaction profile, high yield, short reaction time, simple product isolation, reusable catalysts and close agreement with green chemistry guidelines. Finally, on the basis of our observations and the above mentioned advantages, herein, we think that both of the described biological-based acids and/or catalysts have potential for industrial production.

Experimental

General procedure for the preparation of the organocatalyst 2-carbamoylhydrazine-1-sulfonic acid

In a round-bottomed flask (50 mL) semicarbazide hydrochloride (10 mmol; 1.115 g) in CH₂Cl₂ (3 mL), was drop wise added to chlorosulfonic acid (10 mmol; 1.165 g) and stirred at 0–25 °C for 60 min. Then, the solvent was removed through distillation under reduced pressure and the product was dried under vacuum at 50 °C for 60 min. The white solid product was filtered, washed with CH₂Cl₂ three times, and then dried under vacuum. 2-Carbamoylhydrazine-1-sulfonic acid was characterized by FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry, elemental analysis, TG, DTG, XRD, SEM, TEM, EDX and AFM analysis (Scheme 1).

2-Carbamoylhydrazine-1-sulfonic acid. Mp: 142–144 °C; yield: 98% (1.520 g); spectral data: IR (KBr): ν 3430, 3300, 3096, 1608, 1564, 1491, 1206, 1169, 1042, 881 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 6.59 (brs, 2H, –NH₂), 8.73 (brs, 1H, –OH), 9.35 (brs, 2H, –NH); ¹³C NMR (100 MHz, DMSO-d₆): δ 158.2; MS: m/z = 155 [M]⁺; anal. calcd for CH₅N₃O₄S + H₂O: C, 6.82; H, 3.12; N, 23.34; S, 19.21. Found: C, 6.94; H, 4.08; N, 24.27; S, 18.52.

General procedure for the preparation of the organocatalyst carbamoylsulfamic acid

In a round-bottomed flask (50 mL) urea (10 mmol; 0.600 g) in CH₂Cl₂ (3 mL), was drop wise added to chlorosulfonic acid (10 mmol; 1.165 g) and stirred at 0–25 °C for 60 min. Then, the solvent was removed through distillation under reduced pressure and the product was dried under vacuum at 50 °C for 60 min. The white solid product was filtered, washed with CH₂Cl₂ three times, and then dried under vacuum conditions. Carbamoylsulfamic acid was characterized by FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry, elemental analysis, TG, DTG, XRD, SEM, TEM and EDX analysis (Scheme 1).

Carbamoylsulfamic acid. Mp: 102–104 °C; yield: 98% (1.373 g); spectral data: IR (KBr): ν 3331, 3180, 1700, 1554, 1316, 1233, 1171, 1057, 1024, 883 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆): δ 7.11 (brs, 1H, –OH), 8.73 (brs, 1H, –NH and –NH₂); ¹³C NMR (100 MHz, DMSO-d₆): δ 154.8; MS: m/z = 140 [M]⁺; anal. calcd for CH₄N₂O₄S + H₂O: C, 7.82; H, 3.32; N, 17.49; S, 21.38. Found: C, 7.60; H, 3.82; N, 17.72; S, 20.27.

General procedure for the preparation of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives

To the mixture of aromatic aldehyde (1 mmol) and 1-phenyl-3-methyl-5-pyrazolone (2 mmol), 2-carbamoylhydrazine-1-sulfonic acid or carbamoylsulfamic acid (10 mol%) was added and mixed under solvent-free conditions at 60 °C for the appropriate time as described in Table 4. After completion of the reaction which was observed via TLC (n-hexane/ethyl acetate: 5/2), the mixture was washed with water and the nano organocatalyst was separated, the solid product was then purified by recrystallization from ethanol. All of the desired product(s) were characterized by comparison of their physical data with those of known compounds.

General procedure for the preparation of coumarin-3-carboxylic acid derivatives

To a mixture of Meldrum’s acid (1 mmol) with salicylaldehyde derivatives (1 mmol), 2-carbamoylhydrazine-1-sulfonic acid or carbamoylsulfamic acid (10 mol%) was added and mixed under solvent-free conditions at 50 °C for the appropriate time as described in Table 7. After completion of the reaction which was detected via TLC (n-hexane/ethyl acetate: 5/3), the mixture was washed with water and the nano organocatalyst was separated, the solid product was then purified by recrystallization from ethanol. All of the desired product(s) were characterized by comparison of their physical data with those of known compounds.

General procedure for the preparation of cinnamic acid derivatives

To a mixture of Meldrum’s acid (1 mmol) with aromatic aldehydes (1 mmol), 2-carbamoylhydrazine-1-sulfonic acid or carbamoylsulfamic acid (10 mol%) was added and mixed under solvent-free conditions at 110 °C for the suitable time as described in Table 9. After completion of the reaction which was identified via TLC (n-hexane/ethyl acetate: 5/3), the mixture was washed with water and the nano organocatalyst was separated, the solid product was then purified by recrystallization from ethanol. All of the desired product(s) were characterized by comparison of their physical data with those of known compounds.

Spectral data analysis for compounds

4-((4-(Dimethylamino)phenyl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (Table 4, entry 1). Yellow solid; mp 172–173; ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 2.30 (s, 6H), 2.82 (s, 6H), 4.84 (s, 1H, CH), 6.65 (d, 2H), 7.06 (d, 2H), 7.24 (t, 2H), 7.44 (t, 4H), 7.71 (d, 4H), 12.32 (s, 1H, OH), 13.96 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 12.11, 32.69, 40.85, 113.01, 120.91, 125.94, 128.09, 129.37, 130.43, 138.10, 146.64, 149.28, 157.92; IR (KBr, cm⁻¹): 3460, 3075, 1600, 1582, 1517, 1502, 1481, 1398, 1348, 1282, 1199, 1042, 810, 748, 690; m/z (%) = 480 (M⁺).

4,4′-((4-(Diethoxymethyl)phenyl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) (Table 4, entry 6). Dark violet powder; mp 254–255; ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 1.36 (s, 6H), 2.33 (m, 6H), 3.38 (4H), 4.88 (s, 1H), 5.07 (s, 1H), 7.22 (m, 7H), 7.44 (m, 2H), 7.69 (m, 2H), 7.87 (m, 3H), 12.47 (s, 1H, OH), 14.07 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 12.09, 13.57, 33.23, 58.23, 118.77, 118.89, 121.11, 125.25, 126.14, 127.45, 128.51, 128.82, 129.34, 129.406, 130.00, 133.68, 134.23, 134.84, 136.79, 138.44, 140.45, 146.68, 146.75, 149.92, 152.24; IR (KBr, cm⁻¹): 3473, 3063, 2909, 1616, 1561, 1502, 1499, 1457, 1399, 1368, 1315, 1212, 1119, 995, 855, 811, 747, 687; m/z (%) = 538 (M⁺).

4-((3-Fluorophenyl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (Table 4, entry 7). Cream solid; mp 183–184, ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 2.33 (s, 6H), 4.97 (s, 1H), 7.10 (m, 2H), 7.27 (m, 4H), 7.44 (t, 4H), 7.71 (q, 4H), 12.55 (s, 1H, OH), 13.94 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 12.06, 32.89, 115.10, 115.31, 121.02, 126.08, 129.12, 129.39, 129.45, 129.53, 137.76, 138.63, 138.65, 146.67, 159.93, 162.33; IR (KBr, cm⁻¹): 3444, 3068, 2983, 2930, 1602, 1578, 1503, 1408, 1374, 1347, 1284, 1284, 1216, 1156, 1025, 905, 841, 812, 738, 749, 688; m/z (%) = 454 (M⁺).

Ethyl-3-(bis(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl)-1H-indole-2-carboxylate (Table 4, entry 8). Pale yellow solid; mp 231–233, ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 1.36 (t, 3H), 2.19 (s, 6H), 4.38 (q, 2H), 5.33 (s, 1H, CH) 6.93 (t, 1H), 7.20 (m, 3H), 7.42 (q, 5H), 7.69 (d, 4H), 7.97 (s, 1H), 12.25 (s, 1H, OH), 13.96 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 12.32, 14.76, 32.64, 60.86, 112.68, 119.66, 120.91, 122.33, 123.39, 124.81, 125.81, 126.80, 129.36, 136.72, 147.54, 153.62, 162.26; IR (KBr, cm⁻¹): 3456, 3061, 2924, 2884, 1709, 1622, 1603, 1551, 1497, 1456, 1398, 1319, 1260, 1182, 1151, 1096, 1030, 835, 785, 742, 689; m/z (%) = 548 (M⁺).

4,4′-(Pyridin-4-ylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) (Table 4, entry 9). Dark violet solid; mp 248–250, ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 2.29 (s, 6H), 5.29 (s, 1H, CH), 7.09 (t, 2H), 7.36 (t, 4H), 7.80 (s, 2H), 7.91 (d, 4H),8.82 (s, 2H), 12.33 (s, 1H, OH), 13.79 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 15.92, 32.89, 111.65, 118.46, 121.16, 123.93, 129.06, 129.45, 139.64, 145.19, 149.45, 162.59; IR (KBr, cm⁻¹): 3352, 3087, 2983, 1651, 1634, 1593, 1481, 1319, 1163, 999, 813, 768; m/z (%) = 435 (M⁺).

4-((3-Hydroxy-5-methyl-1-phenyl-1H-pyrazol-4-yl)(3-phenoxyphenyl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (Table 4, entry 19). Cream solid; mp 194–195; ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 2.31 (s, 6H), 4.99 (s, 1H, CH), 6.79 (d, 1H), 7.02 (m, 5H), 7.28 (m, 5H), 7.44 (t, 4H), 7.68 (d, 4H),12.50 (s, 1H, OH) 13.98 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 12.01, 33.32, 116.28, 117.99, 118.86, 121.06, 122.88, 123.73, 126.15, 129.40, 130.13, 130.35, 137.63, 144.90, 146.74, 156.80, 156.85; IR (KBr, cm⁻¹): 3434, 3070, 2923, 1598, 1578, 1498, 1439, 1371, 1253, 1224, 1161, 1019, 787, 752, 685; m/z (%) = 529 (M⁺).

4-(1-(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-methyl-3-phenylallyl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (Table 4, entry 20). Pale yellow solid; mp 163–164; ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 1.79 (s, 3H), 2.29 (s, 6H), 4.33 (s, 1H, CH), 6.36 (s, 1H), 7.25 (m, 6H), 7.44 (t, 4H), 7.72 (d, 4H), 12.39 (s, 1H, OH), 13.89 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 12.05, 17.89, 37.51, 84.28, 121.02, 124.74, 125.97, 126.50, 128.56, 129.22, 129.39, 137.46, 138.44, 146.89, 157.03; IR (KBr, cm⁻¹): 3435, 3058, 2921, 1602, 1579, 1500, 1379, 1266, 1188, 1023, 852, 793, 751, 688; m/z (%) = 476 (M⁺).

4-((4-Hydroxy-3-methoxyphenyl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (Table 4, entry 24). Yellow solid; mp 205–207; ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 2.30 (s, 6H), 3.66 (s, 3H), 4.84 (s, 1H, CH), 6.67 (t, 2H), 6.84 (s, 1H), 7.24 (t, 2H), 7.44 (t, 4H), 7.70 (d, 4H), 8.77 (s, 1H), 12.42 (s, 1H, OH), 14.01 (s, 1H, OH); ¹³C NMR (DMSO-d₆): δ (ppm) 13.01, 33.31, 56.11, 112.38, 115.61, 120.08, 121.03, 126.01, 129.39, 133.73, 145.32, 146.61, 147.63, 154.33; IR (KBr, cm⁻¹): 3456, 3172, 2923, 1600, 1579, 1499, 1415, 1265, 1126, 1039, 782, 752, 692; m/z (%) = 481 (M⁺).

Acknowledgements

The authors gratefully acknowledge the Bu-Ali Sina University Research Council and Center of Excellence in Development of Environmentally Friendly Methods for Chemical Synthesis (CEDEFMCS) for providing support to this work.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra14001c

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