Metal catalyst free one-pot synthesis of 2-arylbenzimidazoles from α-aroylketene dithioacetals

Abstract

An efficient green synthetic approach has been developed towards the synthesis of 2-aryl substituted benzimidazoles from α-aroylketene dithioacetals (AKDTAs) 1 and o-phenylenediamine (OPD) 2. The reaction has been achieved in water with a catalytic amount of acetic acid. 2-Arylbenzimidazoles have been synthesized in remarkable yields under both thermal and microwave conditions. The metal catalyst free condition makes this transformation very green, practical and attractive.

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Introduction

A great number of biologically active molecules contain the benzimidazole scaffold and especially 2-substituted benzimidazole has been found to be biologically more potent. Their application is further extended as poly(ADP-ribose) phosphorylase inhibitors,¹ histamine H4 receptor binders,² antiparasitic,³ cardiovascular,⁴ anticancer,⁵ antimicrobial,⁶ and antihypertensive⁶ agents. In addition, benzimidazoles have been found to have antiulcer activity and inodilator applications (Fig. 1).⁷ The AKDTAs 1 are three carbon synthons, and they are highly functionalized α,β-unsaturated ketones containing both electron withdrawing carbonyl group and electron donating alkylthio substituents well known for their donor–acceptor double bond. The alkylthio group is a very good leaving group and it can be easily replaced by nucleophiles. In several reactions, the AKDTAs 1 behave as α,β-unsaturated carbonyl compounds wherein, depending upon the nucleophile/reaction conditions either 1,2- or 1,4-addition takes place. In acidic media nucleophiles prefer 1,2- addition and it has been extensively used for the synthesis of wide variety of heterocyclic compounds.⁸

Fig. 1 Structures of representative benzimidazole core motif.

Several methods have been reported for the synthesis of 2-substituted benzimidazoles.^9–11 Generally, the conventional method involves the reaction of aryl aldehyde/carboxylic acid or their derivatives with 1,2-diamines to afford the benzimidazole at elevated temperature in the presence of strong acids like polyphosphoric acid,¹² and mineral acid,^13–15 several other catalysts like indium triflate,¹⁶ iodine,¹⁷ cetylpyridinium bromide¹⁸ PEG-400¹⁹ (bromodimethyl)sulfonium bromide,²⁰ ammonium acetate,²¹ cobalt(II) chloride hexahydrate,²² ceric ammonium nitrate²³ and enzymatic catalyst lipozyme²⁴ have been used instead of mineral acids for this cyclocondensation. Recently, substituted benzimidazole has been reported by reacting 2 with aryl aldehydes using 4-OMe-TEMPO as the catalyst under aerobic conditions.²⁵ In addition, C–N bond formation via a cross coupling reaction, and direct C–H activation using a transition metal catalyst have also been reported to construct the benzimidazole skeleton.²⁶

The distinctive methods of assembling these valuable heterocycles are highly dependent on using 2 as the precursor. The literature for the other methods to synthesize 2-arylbenzimidazoles have been comprehensively reviewed (Scheme 1).^27–32

Scheme 1 Strategies for the synthesis of 2-arylbenzimidazoles.

Water mediated organic synthesis has become one of the most attractive protocols in view of environmental aspects. We now report a conceptually novel, simple and effective metal catalyst free direct cyclocondensation of readily available AKDTAs 1 with 2 in the presence of acetic acid as a catalyst in water to afford 4 in excellent yields. The development of a lab route for the synthesis of benzimidazole 4 under metal catalyst free and eco-friendly conditions is worth considering for its practical approach on larger scale operations. Rao et al. reported trisubstituted pyrrole³³ and 3-aroyl coumarin³⁴ by reacting AKDTA with TosMIC and salicylaldehydes, respectively. In continuation of exploring the synthetic potential of AKDTAs 1, we were interested to construct seven membered benzodiazepine derivatives which are pharmacologically and biologically valuable.^35–37

Following the literature,³⁴ a variety of AKDTAs 1 have been synthesized (Table 1). Further, a mixture of AKDTA 1m and 2 was heated in the presence of glacial acetic acid (g/v) at 100 °C for 30 min (Scheme 2). The reaction went smoothly and the crude product was purified by recrystallization with ethanol.

Table 1 Synthesis of AKDTA 1a–v³⁴

Entry	Ar		Yield^a (%)
a Isolated yield after recrystallization.
1	C6H5	1a	88
2	2-Naphthyl	1b	92
3	1-Naphthyl	1c	85
4	4-ClC6H4	1d	92
5	4-CH3C6H4	1e	82
6	Ferrocenyl	1f	85
7	Pyrenyl	1g	80
8	3-NO2C6H4	1h	80
9	3-OCH3C6H4	1i	85
10	2-FC6H4	1j	84
11	3-CF3C6H4	1k	85
12	4-BrC6H4	1l	80
13	4-OCH3C6H4	1m	80
14	2,4-Cl2C6H3	1n	82
15	3,4-F2C6H3	1o	83
16	3,4-Cl2C6H3	1p	79
17	3-BrC6H4	1q	84
18	2-CF3C6H4	1r	84
19	2-F,5-CF3C6H3	1s	70
20	4-IC6H4	1t	77
21	2-F,4-CF3C6H3	1u	72
22	3-CF3,4-ClC6H3	1v	77

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Scheme 2 Cyclocondensation between 1m and 2 in AcOH.

The isolated product was well characterized by ¹H and ¹³C NMR spectra. Anticipating the compound to be 3, the ¹H NMR spectrum displayed a singlet at δ 12.86 for the aromatic NH-proton and one singlet at δ 3.82 for OMe group, a pair of doublets at δ 7.09 and 8.09 ppm with mutual coupling constant J = 8.8 Hz for the two CH protons of the phenyl group of 1m. Two multiplets were appeared at δ 7.14–7.15 and 7.46–7.59 for the CH aromatic protons of 2. But no peak was noticed for the SMe group and the olefinic proton at δ 2.48 ppm and δ 6.86 ppm. Thus the NMR data do not match with compound 3 but perfectly match with 4m and the mass spectrum [m/z 225 (M + 1)] also confims the formation of benzimidazole. Extensive literature studies revealed that this is the first report to the synthesis of 2-arylbenzimidazole 4 from AKDTA 1. Some of the earlier reports for the synthesis of 2-arylbenzimidazole involve the use of expensive metal catalysts, more reaction time and steps and expensive reagents. The advantages of the present method are that it is metal catalyst free with less reaction time and excellent yields. All of the starting materials of AKDTAs 1 are solids and stable, with high melting points and can be easily prepared with simple reaction techniques. Hence, we report the synthesis of 2-arylbenzimidazole by a conceptually novel method of cyclocondensation between AKDTAs 1 and 2. The cyclocondensation was optimized with 4, which was observed through several reactions between AKDTA 1 and 2 (Table 2).

Table 2 Optimization of the reaction conditions towards the synthesis of 4 from 1 and 2

Entry	Solvent	Catalyst (mol%)	Temp. (°C)	Time	Yield (%)^d
a Reaction failed to occur.b Unreacted 1 & 2 recovered.c Complex reaction mixture.d Isolated yield.e Reaction performed at microwave (MW, 120 W, 100 °C).
1	None	None	100	3 h	Nr^a
2	None	AcOH (100)	Rt	72 h	60^b
3	None	AcOH(100)	100	15 min	75
4	None	AcOH (40)	100	30 min	87
5	None	AcOH (30)	100	30 min	65^b
6	None	Formic acid (50)	80	3 h	—^c
7	EtOH	None	90	3 h	Nr^a
8	EtOH	AcOH (40)	90	3 h	60^b
9	MeCN	AcOH (40)	80	2 h	75^b
10	MeCN	Yb(OTf)3 (50)	80	5 h	65^b
11	DMF	Yb(OTf)3 (50)	100	5 h	75^b
12	EtOH	p-TsOH (40)	100	30 min	83
13	EtOH	p-TsOH (40, MW)^e	100	2 min	85
14	H2O	p-TsOH (MW)	100	2 min	50
15	H2O	H2SO4 (1 M)	100	30 min	—^c
16	H2O	HCl (1 M)	100	30 min	50^b
17	H2O	AcOH (100)	100	1 h	87
18	H2O	AcOH (40)	Rt	120 h	20^b
19	H2O	AcOH (40)	100	2 h	95

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Once 4m had been synthesized, several cyclocondensations were tried by variation of reaction conditions (Table 2). The reaction time increased gradually when we reduced the amount of AcOH. The absence of acetic acid did not give the product 4m (Table 2, entry 1). We examined the mild Lewis acid ytterbium(III) trifluoromethanesulfonate (Yb(OTf)₃) with two different solvents to afford 4m in 65 and 75% yields (Table 2, entry 10 & 11). With a catalytic amount of p-TsOH in ethanol, the reaction proceeded smoothly in both thermal (30 min) and microwave (MW, 2 min) conditions with good yield (Table 2, entry 12–13). The drawback of this condition is in water/p-TsOH media under microwave condition only 50% of product was observed (Table 2, entry 14). In HCl, the yield was very low and H₂SO₄ and formic acid media did not give the desired product (Table 2, entry 15–16 & 6). The reaction was performed in ethanol, acetonitrile and water as solvents in the presence of AcOH (40 mol%) at 100 °C. Among the above solvents, a mixture of water–AcOH (40 mol%) gave 4m in maximum yield (95%, Table 2, entry 19). The optimal reaction conditions were a result of 2-(4-methoxyphenyl)-1H-benzo[d]imidazole 4m with 2 in the presence of water–AcOH (40 mol%) at 100 °C for 2 h. Overall, the synthesis of 2-arylbenzimidazoles from AKDTA 1 and 2 proceeds only in the presence of acid medium.

In the next step, variation of the aryl groups was studied and several 2-arylbenzimidazole derivatives 4a–v were synthesized using the optimal reaction conditions (Table 3). Halogen substituted aryls and polyaryls such as 1 and 2-naphthyl, pyrene and ferrocene substituted benzimidazoles were consecutively investigated and the yields were excellent. Some of the final products 4a,c,f–g,j,l and 4t were obtained as pure crystalline products after simple work-up with saturated sodium bicarbonate solution. Later, we carried out the reaction between 1 and 2 under microwave irradiation at 100 °C for 5 min to furnish 4a–v in good to excellent yields (78–90%, Table 3). There is not much difference in the yield of the products, when compared with thermal conditions. Thus the shorter reaction time and good to excellent yields encouraged us to repeat all the reactions under microwave irradiation (Table 3).

Table 3 Synthesis of 4a–v from 1 and 2 in H₂O–AcOH (40 mol%) medium for both thermal and MW conditions^a

Entry	Ar		Yield
			Thermal (%)	MW^c (%)
a All reactions carried out with 1 (1 mmol), 2 (1 mmol), AcOH (40 mol%), water at 100 °C (i) thermal 2 h, (ii) MW 5 min.b Yields after recrystallization.c Isolated yield.
1	C6H5	4a	95^b	90
2	2-Naphthyl	4b	92	88
3	1-Naphthyl	4c	93^b	87
4	4-ClC6H4	4d	88	82
5	4-CH3C6H4	4e	87	82
6	Ferrocenyl	4f	88^b	83
7	Pyrenyl	4g	90^b	87
8	3-NO2C6H4	4h	89	82
9	3-OCH3C6H4	4i	88	83
10	2-FC6H4	4j	82^b	79
11	3-CF3C6H4	4k	84	80
12	4-BrC6H4	4l	90^b	85
13	4-OCH3C6H4	4m	90	88
14	2,4-Cl2C6H3	4n	85	81
15	3,4-F2C6H3	4o	84	78
16	3,4-Cl2C6H3	4p	83	80
17	3-BrC6H4	4q	89	84
18	2-CF3C6H4	4r	83	79
19	2-F,5-CF3C6H3	4s	80	78
20	4-IC6H4	4t	90^b	86
21	2-F,4-CF3C6H3	4u	87	82
22	3-CF3,4-ClC6H3	4v	87	83

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There are number of mechanisms envisioned for the formation of 2-arylbenzimidazole 4 from o-phenylenediamine 2 with aldehyde or acid or acid chloride etc. Based on the results, we propose a plausible mechanism for the one-pot synthesis of 4 by the cyclocondensation of AKDTA 1 and 2 (Scheme 3). When the mixture of AKDTA 1 and 2 with catalytic glacial acetic acid was heated at 100 °C, initially 1 is protonated followed by instantaneous nucleophilic addition of an amine group of 2 at C-1 position to give imine(II). This imine formation makes the C-1 position more electron deficient and attracts further nucleophilic addition by another amine group of 2 to afford a five membered heterocycle 2-(2,2-bis(methylthio)vinyl)-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole(III). In order to achieve the aromaticity, elimination of ethynyl(methyl)sulfane 5 by cleavage of the C–C bond of the ketene group and MeSH 6 has occurred to afford 4 in excellent yields. Elimination of 5 and 6 is the driving force for the formation of 4.

Scheme 3 Plausible mechanism for the two component cyclocondensation.

Conclusions

In summary, we have demonstrated the synthesis of substituted arylbenzimidazoles from AKDTAs 1a–v and readily available 2 under mild and green medium in excellent yields for both thermal and MW conditions. It is noteworthy that this methodology is very simple, less time consuming, metal catalyst free, involving eco-friendly solvent and milder reaction conditions. The economical and environmental advantages of this protocol adds practical value for industrial applications.

Experimental section

General methods

The melting points reported in this work are uncorrected. Unless stated otherwise, solvents and chemicals were obtained from commercial sources and used without further purification. The ¹H and ¹³C NMR spectra of the new compounds were measured at 300 or 400 MHz in DMSO-d₆ and CDCl₃. Chemical shifts are reported as δ values (ppm) relative to tetramethylsilane (δ 0.0) as internal standard. Mass spectra were obtained using an electrospray ionization (ESI) mass spectrometer and recorded in positive and negative mode. Infrared spectra were recorded on an FT-IR spectrometer with the major peaks listed. HRMS (ESI-TOF) analyses were recorded on a mass spectrometer. Petroleum ether employed in column chromatographic purification refers to the fraction which boils at 40–60 °C. Microwave reactions have been carried out in a Biotage Microwave Synthesizer.

General procedure for the preparation of 3,3-bis(methylthio)-1-arylprop-2-en-1-one (1a–v). To a stirred suspension of freshly prepared sodium tert-butoxide (6.0 g, 0.0625 mol) in dry benzene (5 ml) at 0 °C a solution of arylethanone (3 g, 0.0250 mol) and carbon disulfide (2.87 g, 0.0375 mol) in dry benzene (5 ml) was added through a pressure equalizer funnel and the mixture was vigorously stirred at 0 °C for 90 min. Appearance of a reddish solid in the reaction medium indicated the formation of disodium 3-oxo-3-(3-phenyl)-1-propene-1,1-dithiolate. A solution of methyl iodide (4.26 g, 0.030 mol) in dry benzene (5 ml) was carefully added to this suspension, drop-wise over 10 min at 0 °C and the reaction mixture was allowed to stir at 0 °C for 90 min. After completion of the reaction (TLC; hexanes : EtOAc = 7 : 3), the mixture was transferred into a 100 ml beaker containing 50 g of crushed ice and the contents of the beaker were stirred well. A light yellow coloured solid that formed was filtered and washed with water (10 ml × 3). The crude solid was re-crystallized from EtOH to furnish 3.10 g of 1,1-di(methylsulfanyl)-3-(aryl)-1-propen-3-one in 80–92% yield as light yellow colored crystals.
3,3-Bis(methylthio)-1-phenylprop-2-en-1-one³⁴ (1a). Pale yellow solid; yield 88%, mp. 94–96 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.48 (s, 3H), 2.64 (s, 3H), 6.86 (s, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 6.8 Hz, 1H), 7.94 (m, 2H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.9, 17.2, 109.3, 127.6, 128.3, 131.6, 139.2, 166.3, 185.5. LC-MS calcd m/z 224, found 225 [(M + 1)]⁺.
3,3-Bis(methylthio)-1-(naphthalen-2-yl)prop-2-en-1-one³⁴(1b). Yellow solid; yield 92%, mp. 96–98 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.71 (s, 3H), 7.05 (s, 1H), 7.57–7.64 (m, 2H), 7.95–8.02 (m, 3H), 8.10 (d, J = 7.2 Hz, 1H), 8.62 (s, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.1, 17.4, 109.6, 124.3, 126.5, 127.6, 127.7, 128.4, 129.3, 132.6, 134.9, 136.6, 166.3, 185.5. LC-MS calcd m/z 274, found 275 [(M + 1)]⁺.
3,3-Bis(methylthio)-1-(naphthalen-1-yl)prop-2-en-1-one³⁴ (1c). Yellow solid; yield 85%, mp. 79–82 °C; ¹H NMR (300 MHz, CDCl₃) δ_H: 2.46 (s, 3H), 2.57 (s, 3H), 6.56 (s, 1H), 7.45–7.54 (m, 2H), 7.70 (d, J = 8 Hz, 1H), 7.92 (d, J = 12 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.8, 17.1, 113.5, 124.5, 125.8, 126.0, 126.8, 128.1, 130.1, 130.7, 133.6, 138.9, 165.9, 189.3. LC-MS calcd m/z 274, found 275 [(M + 1)]⁺.
1-(4-Chlorophenyl)-3,3-bis(methylthio)prop-2-en-1-one³⁴ (1d). Yellow solid; yield 92%, mp. 104–106 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.47 (s, 3H), 2.65 (s, 3H), 6.84 (s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.4 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.9, 17.3, 108.9, 128.6, 129.0, 137.7, 183.8.* LC-MS calcd m/z 258, found 259 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
3,3-Bis(methylthio)-1-p-tolylprop-2-en-1-one³⁴ (1e). Yellow solid; yield 82%, mp. 98–100 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.63 (s, 3H), 2.78 (s, 1H), 6.84 (s, 1H), 7.23 (d, J = 8.8 Hz, 2H), 7.64 (d, J = 8.8 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.0, 17.3, 55.4, 21.5, 109.6, 127.8, 129.1, 136.7, 142.3, 165.5, 185.4. LC-MS calcd m/z 238, found 239 [(M + 1)]⁺.
3,3-Bis(methylthio)-1-ferrocenyl-2-propen-1-one³⁴ (1f). Yellow solid; yield: 85%, mp. 112–114 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.42 (s, 3H), 2.60 (s, 3H), 4.16 (s, 4H), 4.50 (s, 1H), 4.83 (s, 2H), 6.41 (s, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.9, 17.4, 69.0, 69.8, 71.6, 81.6, 111.3, 160.9, 189.3. LC-MS calcd m/z 332, found 333 [(M + 1)]⁺.
3,3-Bis(methylthio)-1-pyrenyl-2-propen-1-one³³ (1g). Yellow solid; yield: 80% yield, mp. 150–152 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.56 (s, 3H), 2.61 (s, 3H), 6.82 (s, 1H), 7.35 (s, 1H), 8.13 (t, J = 8 Hz, 1H), 8.22–8.29 (m, 3H), 8.33–8.38 (m, 4H), 8.63 (d, J = 9.2 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ_C: 15.0, 17.3, 114.2, 124.2, 124.8, 124.9, 125.5, 126.2, 127.1, 128.3, 128.5, 128.7, 128.8, 130.6, 132.7, 135.7, 189.6.* LC-MS calcd m/z 348, found 349 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
3,3-Bis(methylthio)-1-(3-nitrophenyl)prop-2-en-1-one³⁸ (1h). Yellow solid; yield: 80%, mp. 110–112 °C; ¹H NMR (400 MHz, CDCl₃) δ_H: 2.57 (s, 3H), 2.62 (s, 3H), 6.74 (s, 1H), 7.64 (t, J = 8 Hz, 1H), 8.26 (d, J = 8 Hz, 1H), 8.35 (d, J = 8 Hz, 1H), 8.71 (s, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.5, 16.8, 107.3, 121.7, 125.3, 128.9, 132.9, 140.1, 147.6, 169.6, 181.9. LC-MS calcd m/z 269, found 270 [(M + 1)]⁺.
1-(3-Methoxyphenyl)-3,3-bis(methylthio)prop-2-en-1-one³⁸ (1i). Yellow solid; yield 84%, mp. 88–90 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.65 (s, 3H), 3.80 (s, 3H), 6.83 (s, 1H), 7.13 (d, J = 8 Hz, 1H), 7.41 (t, J = 8 Hz, 2H), 7.54 (d, J = 8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.9, 17.3, 55.3, 109.4, 112.4, 117.9, 119.9, 129.3, 140.7, 159.7, 166.5, 185.2. LC-MS calcd m/z 254, found 255 [(M + 1)]⁺.
1-(2-Fluorophenyl)-3,3-bis(methylthio)prop-2-en-1-one³⁸ (1j). Yellow solid; yield: 84%, mp. 70–72 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.50 (s, 3H), 2.58 (s, 3H), 6.66 (s, 1H), 7.28–7.33 (m, 2H), 7.55–7.61 (m, 1H), 7.75 (t, J = 8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.1, 17.3, 113.2, 113.3, 116.0, 116.3, 124.4, 127.5, 127.7, 131.2, 132.9, 133.1, 158.8, 162.1, 167.0, 182.3. LC-MS calcd m/z 242, found 243 [(M + 1)]⁺.
3,3-Bis(methylthio)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one³⁸ (1k). Yellow solid; yield: 85%, mp. 88–90 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.68 (s, 3H), 6.90 (s, 1H), 7.74 (t, J = 8 Hz, 1H), 7.92 (d, J = 8 Hz, 1H), 8.18 (s, 1H), 8.28 (d, J = 7.6 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.0, 17.3, 108.4, 124.4, 128.0, 128.9, 130.7, 131.1, 139.9, 168.8, 183.7. LC-MS calcd m/z 292, found 293 [(M + 1)]⁺.
1-(4-Bromophenyl)-3,3-bis(methylthio)prop-2-en-1-one³⁹ (1l). Yellow solid; yield: 80%, mp. 100–104 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.50 (s, 3H), 2.66 (s, 3H), 6.84 (s, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 14.4, 16.8, 108.3, 125.8, 129.0, 131.1, 137.5, 167.1, 183.2.* LC-MS calcd m/z 303, found 304 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
1-(4-Methoxyphenyl)-3,3-bis(methylthio)prop-2-en-1-one³⁹ (1m). Yellow solid; yield: 80%, mp. 100–102 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.45 (s, 3H), 2.63 (s, 3H), 3.82 (s, 1H), 6.84 (s, 1H), 7.00 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.1, 17.3, 55.4, 109.8, 113.7, 129.4, 132.2, 162.6, 164.6, 184.6.* LC-MS calcd m/z 254, found 255 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
1-(2,4-Dichlorophenyl)-3,3-bis(methylthio)prop-2-en-1-one⁴⁰ (1n). Yellow solid; yield: 82%, mp. 108–110 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.54 (s, 3H), 6.44 (s, 1H), 7.50 (d, J = 9.2 Hz, 1H), 7.58 (d, J = 8 Hz, 1H), 7.68 (s, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.0, 17.2, 112.5, 127.2, 129.9, 130.8, 131.7, 136.2, 138.8, 167.7, 184.9. LC-MS calcd m/z 293, found 294 [(M + 1)]⁺.
1-(3,4-Difluorophenyl)-3,3-bis(methylthio)prop-2-en-1-one (1o). Yellow solid; yield: 83%, mp. 137 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.68 (s, 3H), 6.81 (s, 1H), 7.43–7.48 (m, 1H), 7.65 (d, J = 6.8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.0, 17.3, 106.7, 108.1, 110.3, 110.7, 142.5, 161.1, 161.3, 164.4, 164.6, 169.5, 182.3. LC-MS calcd m/z 260 found 261 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₁H₁₀F₂OS₂Na [M + Na]⁺ 283.0039 found 283.0034.
1-(3,4-Dichlorophenyl)-3,3-bis(methylthio)prop-2-en-1-one (1p). Yellow solid; yield: 79%, mp. 118–120 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.48 (s, 3H), 2.67 (s, 3H), 6.83 (s, 1H), 7. 73 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 8.14 (s, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.1, 17.4, 108.1, 126.7, 129.6, 130.4, 132.8, 135.9, 138.9, 168.9, 182.6. LC-MS calcd m/z 293, found 294 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₁H₁₀Cl₂OS₂Na [M + Na]⁺ 314.9448 found 314.9440.
1-(3-Bromophenyl)-3,3-bis(methylthio)prop-2-en-1-one (1q). Yellow solid; yield: 84%, mp. 78–80 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.48 (s, 3H), 2.67 (s, 3H), 6.83 (s, 1H), 7.46 (t, J = 8 Hz, 1H), 7.75 (d, J = 8 Hz, 1H), 7.96 (d, J = 7.6 Hz, 1H), 8.07 (s, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.1, 17.5, 108.7, 122.7, 126.3, 130.1, 130.8, 134.5, 141.3, 168.3, 183.9. LC-MS calcd m/z 303, found 304 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₁H₁₁BrOS₂Na [M + Na]⁺ 324.9332 found 324.9326.
3,3-Bis(methylthio)-1-(2-(trifluoromethyl)phenyl)prop-2-en-1-one (1r). Pale yellow solid; yield: 84%, mp. 108–110 °C; ¹H NMR (300 MHz, CDCl₃) δ_H: 2.46 (s, 3H), 2.54 (s, 3H), 6.26 (s, 1H), 7.27–7.61 (m, 3H), 7.69 (d, J = 8 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ_C: 16.9, 19.1, 78.6, 79.0, 79.4, 114.1, 128.2, 128.3, 129.1, 130.1, 131.3, 133.7, 143.4, 169.8, 189.5. LC-MS calcd m/z 292, found 293 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₂H₁₁F₃OS₂Na [M + Na]⁺ 315.0101 found 315.0093.
1-(2-Fluoro-5-(trifluoromethyl)phenyl)-3,3-bis(methylthio)prop-2-en-1-one (1s). Yellow solid; yield: 70%, mp. 88–90 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.51 (s, 3H), 2.58 (s, 3H), 6.66 (s, 1H), 7.57 (t, J = 9.2 Hz, 1H), 7.95–8.02 (m, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.3, 17.4, 112.4, 117.1, 119.4, 124.8, 126.3, 127.5, 128.2, 129.2, 129.9, 160.8, 163.3, 169.6, 180.4. LC-MS calcd m/z 310, found 311 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₂H₁₀F₄OS₂Na [M + Na]⁺ 333.0007 found 333.0003.
1-(4-Iodophenyl)-3,3-bis(methylthio)prop-2-en-1-one (1t). Yellow solid; yield: 77%, mp. 88–90 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.64 (s, 3H), 6.82 (s, 1H), 7.73 (d, J = 8 Hz, 1H), 7.86 (d, J = 8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.1, 17.4, 99.1, 108.7, 128.0, 129.3, 137.7, 138.7, 167.7, 184.68.* LC-MS calcd m/z 350, found 351 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₁H₁₁IOS₂Na [M + Na]⁺ 372.9194 found 372.9190. [* – Two carbon signals have merged together.]
1-(2-Fluoro-4-(trifluoromethyl)phenyl)-3,3-bis(methylthio)prop-2-en-1-one (1u). Yellow solid; yield: 72%, mp. 84–86 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.51 (s, 3H), 2.57 (s, 3H), 6.63 (s, 1H), 7.67 (d, J = 8 Hz, 1H), 7.79 (d, J = 10.4 Hz, 1H), 7.92 (t, J = 8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.2, 17.4, 112.4, 113.8, 113.9, 114.0, 121.3, 121.4, 121.5, 124.3, 130.7, 132.2, 134.3, 134.7, 158.6, 161.2, 169.6, 180.7. LC-MS calcd m/z 310, found 311 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₂H₁₀F₄OS₂Na [M + Na]⁺ 333.0007 found 333.0001.
1-(4-Chloro-3-(trifluoromethyl)phenyl)-3,3-bis(methylthio)prop-2-en-1-one (1v). Yellow solid; yield: 77%, mp. 126–128 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H: 2.49 (s, 3H), 2.68 (s, 3H), 6.88 (s, 1H), 7.85 (d, J = 8 Hz, 1H), 8.25 (s, 1H), 8.29 (d, J = 8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ_C: 15.2, 17.5, 107.9, 121.2, 123.9, 126.8, 126.9, 128.5, 128.8, 131.7, 135.0, 135.6, 137.9, 169.8, 182.7. LC-MS calcd m/z 326, found 327 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₂H₁₀ClF₃OS₂Na [M + Na]⁺ 348.9711 found 348.9708.

General method for the synthesis of (E)-aryl-1H-benzo[d]-benzimidazole (4a–v).
Method I (conventional heating method). To the mixture of AKDTA 1 (1 mmol), o-phenylenediamine 2 (1 mmol), acetic acid (40 mol%) in water (6 ml) was added and heated at 100 °C for 2 h. The reaction mixture was treated with sodium bicarbonate and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with water, dried and concentrated under rotary vacuum evaporation. The crude residue was recrystallized to obtain pure solid product 4a–v (80–95% yields).
Method II (microwave irradiation method). A 10 ml glass vial sealed by a septum, containing a mixture of AKDTA 1 (1 mmol) o-phenylenediamine 2 (1 mmol), and acetic acid (40 mol%) in water (6 ml) was placed in a microwave synthesizer. The vial was then subjected to microwave irradiation programmed at 120 W, 100 °C with 1 bar pressure. After completion of the reaction (5 min), the vial was cooled to room temperature and extracted with ethyl acetate and the crude was purified by recrystallization in ethanol to yield pure 4a–v (78–90%).
2-Phenyl-1H-benzo[d]imidazole⁴¹ (4a). Off white crystalline solid; yield: 95% (thermal), 90% (MW), mp. 296 °C; UV λ_max (MeOH) = 241 nm (log ε = 2.39), 202 nm (log ε = 2.61). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.15–7.22 (m, 2H), 7.46–7.75 (m, 4H), 7.65 (d, J = 7.6 Hz, 1H), 8.16 (d, J = 6.8 Hz, 2H), 12.86 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 111.3, 118.9, 121.7, 122.5, 126.4, 128.9, 129.8, 130.2, 135.0, 143.8, 151.2. LC-MS calcd m/z: 194, found 195 [(M + 1)]⁺.
2-(Naphthalene-2-yl)-1H-benzo[d]imidazole⁴² (4b). Off white solid; yield: 92% (thermal), 90% (MW), mp. 214–215 °C; UV λ_max (MeOH) = 316 nm (log ε = 2.75), 281 nm (log ε = 2.65), 241 nm (log ε = 2.88). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.19–7.23 (m, 2H), 7.54–7.69 (m, 4H), 7.97–8.08 (m, 3H), 8.30 (d, J = 8.4 Hz, 1H), 8.72 (s, 1H), 13.03 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 129.0, 131.1, 131.6, 131.8, 132.7, 133.3, 133.3, 137.9, 138.6, 156.7.* LC-MS calcd m/z: 244 found 245 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(Naphthalene-1-yl)-1H-benzo[d]imidazole⁴¹ (4c). Off white solid; yield: 93% (thermal), 87% (MW), mp 270–272 °C; UV λ_max (MeOH) = 306 nm (log ε = 2.58), 226 nm (log ε = 2.88). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.22–7.26 (m, 2H), 7.58–7.68 (m, 5H), 7.80–8.04 (m, 2H), 8.08 (d, J = 8.4 Hz, 1H), 9.10 (d, J = 7.6 Hz, 1H), 12.92 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 122.4, 125.5, 126.6, 126.8, 127.3, 128.3, 128.7, 130.4, 131.1, 134.0, 151.8. LC-MS calcd m/z: 244, found 245 [(M + 1)]⁺.
2-(4-Chlorophenyl)-1H-benzo[d]imidazole⁴¹ (4d). Off white solid; yield: 88% (thermal), 82% (MW), mp. 290–292 °C; UV (MeOH) λ_max = 307 nm (log ε = 2.77), 245 nm (log ε = 2.45). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.20 (s, 2H), 7.52 (d, J = 6.8 Hz, 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.66 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 12.94 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 122.5, 128.3, 129.1, 129.3, 135.3, 150.7.* LC-MS calcd m/z: 228, found 229 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-p-Tolyl-1H-benzo[d]imidazole⁴¹ (4e). Off white solid; yield: 87% (thermal), 82% (MW), mp. 275–277 °C; UV λ_max (MeOH) = 304 nm (log ε = 2.77), 243 nm (log ε = 2.53). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.13–7.20 (m, 2H), 7.34 (d, J = 8 Hz, 2H), 7.49 (d, J = 6.4 Hz, 1H), 7.62 (d, J = 7.6 Hz, 1H), 8.05 (d, J = 8 Hz, 2H), 12.76 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 22.0, 112.8, 127.4, 128.4, 130.3, 140.4, 152.5.* LC-MS calcd m/z: 208, found 209 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(Ferrocenyl-2-yl)-1H-benzo[d]imidazole⁴³ (4f). Off white solid; yield: 88% (thermal), 83% (MW), mp. 300 °C; UV λ_max (MeOH) = 304 nm (log ε = 2.70), 206 nm (log ε = 2.93). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 4.08 (s, 4H), 4.45 (s, 2H), 5.02 (s, 2H), 7.08–7.15 (m, 2H), 7.42 (d, J = 6.8 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 12.30 (s, 1H). ¹³C NMR (100 MHz, DMSO-d₆) δ_C: 60.7, 69.8, 70.2, 74.8, 110.9, 118.4, 121.8, 153.4. LC-MS calcd m/z: 303, found 304 [(M + 1)]⁺.
2-(Pyren-2-yl)-1H-benzo[d]imidazole (4g). Off white solid; yield: 90% (thermal), 87% (MW), mp. 300 °C; UV λ_max (MeOH) = 351 nm (log ε = 3.51), 278 nm (log ε = 2.69), 241 nm (log ε = 2.87). IR (KBr): 3423, 3043, 1743, 1649, 1421, 1278, 1018, 842, 746 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.26–7.28 (m, 2H), 7.71–7.74 (m, 2H), 8.20 (t, J = 7.6 Hz, 1H), 8.27–8.37 (m, 3H), 8.45 (d, J = 8 Hz, 1H), 8.56 (d, J = 8 Hz, 1H), 9.51 (d, J = 9.2 Hz, 1H), 13.13 (s, 1H). ¹³C NMR (100 MHz, DMSO-d₆) δ_C: 122.6, 124.2, 124.8, 125.1, 125. 3, 126.0, 126.1, 126.4, 127.1, 127.8, 128.9, 129.1, 130.8, 131.4, 132.0. LC-MS calcd m/z: 318, found 319 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₂₃H₁₆N₂Na [M + Na]⁺ 343.1211 found 343.1208.
2-(3-Nitrophenyl)-1H-benzo[d]imidazole⁴⁴ (4h). Off white solid; yield: 89% (thermal), 82% (MW), mp. 208–210 °C; UV λ_max (MeOH) = 306 nm (log ε = 2.64), 245 nm (log ε = 2.52). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.20–7.28 (m, 2H), 7.57 (d, J = 7.6 Hz, 1H), 7.71 (d, J = 8 Hz, 1H), 7.85 (t, J = 8 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.60 (d, J = 8 Hz, 1H), 9.00 (s, 1H), 13.25 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 111.8, 119.5, 121.3, 122.3, 123.4, 124.1, 130.4, 132.2, 132.7, 135.4, 143.9, 148.6, 149.4. LC-MS calcd m/z: 239, found 240 [(M + 1)]⁺.
2-(3-Methoxyphenyl)-1H-benzo[d]imidazole⁴⁵ (4i). Off white solid; yield: 88% (thermal), 83% (MW), mp. 210–212 °C; UV λ_max (MeOH) = 306 nm (log ε = 2.74), 210 nm (log ε = 2.91). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 3.85 (s, 3H), 7.03–7.06 (m, 1H), 7.19 (s, 2H), 7.44 (t, J = 8.4 Hz, 1H), 7.53 (s, 1H), 7.64 (s, 1H), 7.73–7.75 (m, 2H), 12.84 (s, 1H). ¹³C NMR (100 MHz, DMSO-d₆) δ_C: 55.8, 111.9, 116.3, 119.2, 122.6, 130.6, 131.9, 151.6, 160.1.* LC-MS calcd m/z: 224, found 225 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(2-Fluorophenyl)-1H-benzo[d]imidazole (4j). Off white solid; yield: 82% (thermal), 79% (MW), mp. 205–206 °C; UV λ_max (MeOH) = 303 nm (log ε = 2.87), 206 nm (log ε = 3.02). IR (KBr): 3425, 2854, 1739, 1423, 1018, 748 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.12–7.25 (m, 2H), 7.36–7.45 (m, 2H), 7.52–7.58 (m, 2H), 7.68 (d, J = 7.2 Hz, 1H), 8.23 (t, J = 8 Hz, 1H), 12.53 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 115.9, 116.3, 117.3, 117.5, 125.1, 125.1, 130.1, 130.1, 131.5, 131.6, 131.6, 146.9, 158.6, 161.9. LC-MS calcd m/z: 212, found 213 [(M + 1)]⁺ HRMS (ESI-TOF) calcd for C₁₃H₉FN₂Na [M + Na]⁺ 235.0647 found 235.0641.
2-(3-(Trifluoromethyl)phenyl)-1H-benzo[d]imidazole⁴⁶ (4k). Off white solid; yield: 84% (thermal), 80% (MW), mp. 206–208 °C; UV λ_max (MeOH) = 306 nm (log ε = 2.77), 206 nm (log ε = 2.90). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.19–7.26 (m, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 7.2 Hz, 1H) 7.77–7.85 (m, 2H), 8.46 (d, J = 7.6 Hz, 1H), 8.51 (s, 1H), 13.12 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 111.4, 119.3, 122.2, 123.1, 123.6, 126.0, 129.4, 130.0, 130.7, 131.1, 131.4, 135.2, 150.3. LC-MS calcd m/z: 262, found 263 [(M + 1)]⁺.
2-(4-Bromophenyl)-1H-benzo[d]imidazole⁴⁴ (4l). Off white solid; yield: 90% (thermal), 85% (MW), mp. 296–298 °C; UV λ_max (MeOH) 308 nm (log ε = 2.72), 246 nm (log ε = 2.46). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.16–7.24 (m, 2H), 7.52 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 8.4 Hz, 2H), 12.94 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 122.6, 123.8, 128.6, 129.7, 132.0, 150.8.* LC-MS calcd m/z: 212, found 213 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(4-Methoxyphenyl)-1H-benzo[d]imidazole⁴⁴ (4m). Off white solid; yield: 90% (thermal), 88% (MW), mp. 225–226 °C; UV λ_max (MeOH) = 307 nm (log ε = 2.82), 248 nm (log ε = 2.52). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 3.82 (s, 3H), 7.09 (d, J = 8.8 Hz, 2H), 7.14–7.15 (m, 2H), 7.46–7.59 (m, 2H), 8.09 (d, J = 8.8 Hz, 2H), 12.68 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 14.6, 122.1, 123.2, 128.4, 151.9, 161.0.* LC-MS calcd m/z: 224, found 225 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(2,4-Dichlorophenyl)-1H-benzo[d]imidazole⁴⁷ (4n). Off white solid; yield: 85% (thermal), 81% (MW), mp. 216–218 °C; UV λ_max (MeOH) = 296 nm (log ε = 2.56), 207 nm (log ε = 2.95). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.23–7.24 (m, 2H), 7.59–7.62 (m, 3H), 7.82 (s, 1H), 7.93 (d, J = 8.4 Hz, 1H), 12.72 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 127.4, 132.2, 133.5, 134.3, 137.6, 137.8, 140.5, 153.2.* LC-MS calcd m/z: 262, found 263 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(3,4-Difluorophenyl)-1H-benzo[d]imidazole (4o). Off white solid; yield: 84% (thermal), 78% (MW), mp. 230 °C; UV λ_max (MeOH) = 306 nm (log ε = 2.69), 242 nm (log ε = 2.39). IR (KBr): 3445, 3300, 1620, 1400, 1200, 1080, 760 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.19–7.28 (m, 2H), 7.36–7.40 (m, 1H), 7.55 (d, J = 8 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.84 (d, J = 7.4 Hz, 2H), 13.05 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 104.9, 105.2, 105.6, 109.6, 109.9, 111.9, 119.6, 122.5, 123.5, 133.8, 133.9, 134.1, 135.3, 143.9, 149.3, 161.4, 161.6, 164.7, 164.88. LC-MS calcd m/z: 230, found 231 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₃H₈F₂N₂Na [M + Na]⁺ 253.0553 found 253.0548.
2-(3,4-Dichlorophenyl)-1H-benzo[d]imidazole (4p). Off white crystalline solid; yield: 83% (thermal), 80% (MW), mp. 235 °C; UV λ_max (MeOH) = 294 nm (log ε = 2.60), 205 nm (log ε = 2.90). IR (KBr): 3439, 3380, 1590, 1590, 1312, 1020, 800 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.23 (t, J = 8.4 Hz, 2H), 7.54 (d, J = 7.2 Hz, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 8.38 (s, 1H), 13.05 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 115.8, 122.7, 127.8, 129.2, 130.2, 132.9, 133.5, 135.5, 139.3, 148.5.* LC-MS calcd m/z: 263, found 264 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₃H₈Cl₂N₂Na [M + Na]⁺ 284.9962 found 284.9955. [* – Two carbon signals have merged together.]
2-(3-Bromophenyl)-1H-benzo[d]imidazole⁴⁴ (4q). Off white solid; yield: 89% (thermal), 84% (MW), mp. 262–264 °C; UV λ_max (MeOH) = 306 nm (log ε = 2.79), 207 nm (log ε = 2.95). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.19–7.27 (m, 2H), 7.50–7.56 (m, 2H), 7.67–7.70 (m, 2H), 8.18 (d, J = 8 Hz, 1H), 8.37 (s, 1H), 13.00 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 155.0, 137.4, 137.2, 135.4, 130.2, 127.5.* LC-MS calcd m/z: 273, found 274 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(2-(Trifluoromethyl)phenyl)-1H-benzo[d]imidazole⁴⁸ (4r). White crystalline solid; yield: 83% (thermal), 79% (MW), mp. 274–276 °C; UV λ_max (MeOH) = 282 nm (log ε = 2.47), 206 nm (log ε = 2.92). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.18–7.26 (m, 2H), 7.52 (d, J = 8 Hz, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.74–7.85 (m, 3H), 7.93 (d, J = 7.6 Hz, 1H), 12.72 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 127.1, 131.1, 133.5, 134.5, 136.5, 137.1, 154.4.* LC-MS calcd m/z: 262, found 263 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(2-Fluoro-5-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole (4s). Off white crystalline solid; yield: 80% (thermal), 78% (MW), mp. 215 °C; UV λ_max (MeOH) = 307 nm (log ε = 2.73), 206 nm (log ε = 2.89). IR (KBr): 3441, 3053, 2924, 1789, 1404, 1332, 1159, 752 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.24–7.30 (m, 2H), 7.61 (d, J = 7.6 Hz), 7.75 (dd, J = 8.4 Hz, J = 7.2 Hz, 2H), 7.94 (d, J = 10.8 Hz, 1H), 8.46 (t, J = 8 Hz, 1H), 12.77 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 105.2, 109.6, 109.9, 111.9, 119.6, 122.5, 123.5, 133.9, 134.1, 135.3, 143.9, 149.3, 161.6, 164.7. LC-MS calcd m/z: 280, found 281 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₄H₈F₄N₂Na [M + Na]⁺ 303.0521 found 303.0516.
2-(4-Iodophenyl)-1H-benzo[d]imidazole⁴⁹ (4t). Off white crystalline solid; yield: 90% (thermal), 86% (MW), mp. 290–292 °C; UV λ_max (MeOH) = 310 nm (log ε = 2.82), 252 nm (log ε = 2.53). ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.16–7.19 (m, 1H), 7.56–7.58 (m, 1H), 7.92 (dd, J = 8 Hz, 8.4 Hz, 2H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 96.2, 122.4, 128.6, 130.2, 137.9, 150.9.* LC-MS calcd m/z: 320, found 321 [(M + 1)]⁺. [* – Two carbon signals have merged together.]
2-(2-Fluoro-4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole (4u). Off white solid; yield: 87% (thermal), 82% (MW), mp. 230 °C; UV λ_max (MeOH) = 308 nm (log ε = 2.75), 206 nm (log ε = 2.85). IR (KBr): 3441, 3086, 1770, 1444, 1332, 1130, 740 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.24–7.30 (m, 2H), 7.61 (d, J = 7.6 Hz, 1H), 7.75 (dd, J = 8.4 Hz, J = 7.2 Hz, 2H), 7.94 (d, J = 10.8 Hz, 1H), 8.46 (t, J = 8 Hz, 1H), 12.77 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 112.4, 113.8, 114.1, 119.4, 121.7, 122.4, 123.5, 131.4, 135.4, 143.2, 157.7, 161.1. LC-MS calcd m/z: 280, found 281 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₄H₈F₄N₂Na [M + Na]⁺ 303.0521 found 303.0516.
2-(4-Chloro-3-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole (4v). Off white solid; yield: 87% (thermal), 83% (MW), mp. 200 °C; UV λ_max (MeOH) = 309 nm (log ε = 2.78), 246 nm (log ε = 2.50). IR (KBr): 3444, 3053, 1618, 1438, 1317, 1180, 743 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆) δ_H: 7.20–7.28 (m, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 8 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.61 (s, 1H), 13.18 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 129.3, 130.6, 133.1, 133.5, 134.4, 135.7, 136.6, 137.6, 154.2.* LC-MS calcd m/z: 296, found 297 [(M + 1)]⁺. HRMS (ESI-TOF) calcd for C₁₄H₈ClF₃N₂Na [M + Na]⁺ 319.0226 found 319.0220. [* – Two carbon signals have merged together.]

Acknowledgements

SS thanks DST-MRP, New Delhi and UGC – MRP, New Delhi for the financial assistances. PD thanks UGC for meritorious fellowship. We thank DST-IRHPA for fundings towards higher resolution NMR spectrometer. We thank Prof. H. Surya Prakash Rao, Department of Chemistry, Pondicherry University, Puducherry for generous help in recording spectra and helpful discussions. SS dedicates this manuscript to his mentor Prof. H. Surya Prakash Rao, Department of Chemistry, Pondicherrry University, Puducherry-14.

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Footnote

† Electronic supplementary information (ESI) available: Copies of representative spectra. See DOI: 10.1039/c3ra47761d

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