research article glycerol containing triacetylborate...

Research ArticleGlycerol Containing Triacetylborate MediatedSyntheses of Novel 2-Heterostyryl Benzimidazole Derivatives:A Green Approach

Ashok Kumar Taduri, P. N. Kishore Babu, and B. Rama Devi

Department of Chemistry, College of Engineering, Jawaharlal Nehru Technological University Hyderabad, Kukatpally,Hyderabad Andhra Pradesh 500 085, India

Correspondence should be addressed to Ashok Kumar Taduri; [email protected]

Received 9 November 2013; Revised 20 February 2014; Accepted 24 March 2014; Published 27 April 2014

Academic Editor: Robert Salomon

Copyright © 2014 Ashok Kumar Taduri et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

A very simple, mild, efficient, and novel green methodology has been developed for the syntheses of some 2-hetero/styryl-benzimidazoles. Title compounds were synthesized by the condensation of 𝑜-phenylenediamine with cinnamic acids at 150–180∘Cfor 5-6 h using glycerol containing triacetylborate (10–20mol%) as the reaction medium. In an alternative approach, condensationof 2-methylbenzimidazole derivatives with aromatic aldehydes was done using glycerol containing triacetylborate (10–20mol%) asthe reaction medium.

1. Introduction

Using solvents in chemical synthesis represents a greaterchallenge in terms of green chemistry and among themsolvents like water, PEG-600, and ionic liquids have provedto be potential green solvents for organic synthesis. In thepast [1], glycerol as solvent has not been used extensively fororganic synthesis and in recent years, various developmentshave been made to prove that glycerol can be used as analternate solvent and can feasibly be considered as an efficientgreen solvent [2, 3]. Cinnamic acids and its derivatives (i-iv) (Figure 1) such as ethyl cinnamate, sodium cinnamate,and benzylcinnamate have century old history as potentialantituberculosis agents [4–7]. Benzimidazole scaffold beingan important pharmacophore and privileged structure inmedicinal chemistry [8, 9], a new series of 5-(bromo/nitro)-2-styryl-benzimidazoles were synthesized earlier using cin-namic acids in ethylene glycol under reflux conditions andshowed good antimicrobial and antitubercular activities (vii)[10, 11]. 2-Styryl-benzimidazoles and its analogues (v) werealso reported as MAO-B inhibitors [12], in which the styrylcompounds were synthesized using 2-methylbenzimidazole

condensed with aromatic aldehydes refluxing at 180∘C for24 h (Figure 1).

Recently, some new styryl benzimidazoles were reportedas probes for imaging neurofibrillary tangles in Alzheimer’sdisease [13], in which new iodo derivatives of styryl-benzimidazoles were prepared by the condensation of sub-stituted 𝑜-phenylenediamines with cinnamaldehydes reflux-ing in DMF [13]. Other methods for the preparation of2-styrylbenzimidazoles involves the use of PPA at 200∘Cgave a low 30% yield [10] and the conventional Phillipsmethod, in which 𝑜-phenylenediamine condensed with cin-namic acids refluxing in 4N HCl, for the synthesis of 2-styrylbenzimidazoles, resulted in the recovery of startingmaterial [10].

The widespread interest in benzimidazole containingskeletons having a wide spectrum of activity has promotedextensive studies for their synthesis. While there are manystrategies available for benzimidazole synthesis, there are afew methods available for the preparation of 2-styryl type ofbenzimidazoles. The earlier methods involve nongreen [14–17] routes like using PPA or high temperatures, long reactiontimes, various work-upmethods, and low yieldsmade to look

Hindawi Publishing CorporationOrganic Chemistry InternationalVolume 2014, Article ID 260726, 9 pageshttp://dx.doi.org/10.1155/2014/260726

2 Organic Chemistry International

O

OH

O O

R

R

N

NH

N N

N N

O

O

O

OO

X X

CH3

O Na− +

(i) (ii) (iii)

(iv) (v) (vi)

Figure 1: Cinnamic acid and its derivatives showing various biological activities.

for other methods for the synthesis of 2-styryl type of benz-imidazoles.Though the abovemethodswere effective in com-pletion of the reaction, but they suffer from eco-friendly prac-tise. Therefore, the discovery of practicable greener routesutilizing easily available starting materials like glycerol andtriacetylborate which were considered as environmentallyfriendly for the synthesis of 2-hetero/styrylbenzimidazolescontinues to attract the attention of researchers.

In continuation of our earlier work on the synthesis of 2-styrylbenzimidazoles, now we wish to extend our approachby using other heterocyclic aldehydes like furfuraldehyde,piperonaldehyde and thiophene-2-aldehyde, and so forth, inaddition to benzaldehyde derivatives, in a very green way byusing glycerol and triacetylborate as green and as a recyclablereaction medium.

2. Materials and Methods

All the reagents used in this work were obtained fromcommercial suppliers. Solvents were freshly distilled beforebeing used. Melting points were determined using a BuchiMelting Point B-545 apparatus and are uncorrected. TLCanalyses were done on glass plates coated with silica gel GF-254 and spotting was done using Iodine/UV lamp. IR spectrawere recorded on a Perkin-Elmer model 446 instrument inKBr phase. 1H NMR were recorded in CDCl

3/DMSO using

400MHz Varian Gemini spectrometer and mass spectrawere recorded on LC-MS spectrometer, model HP5989A. 13CNMR was recorded in DMSO using 100MHz spectrometer.

2.1. General Procedure for the Synthesis of 2-Styryl-benzimidazole Derivatives from O-PDA and CinnamicAcids. An intimate mixture of o-penylenediamine 1 (1.08 g,10mM) was dissolved in a 100mL round bottom flask. Tothis, triacetylborate (0.2 g, 10mol%) was added, followedby the addition of cinnamic acids 2 (10mM) and allowedit to boil at 160–180∘C in oil-bath for 3 h using Dean-Starkapparatus. The completion of the reaction was monitored bychecking TLC. At the end of this period, the reactionmixturewas poured into ice cold water. The pH of the solution was

adjusted to 8.0–10.0. The formed product was filtered, driedand recrystallized by using a suitable solvent.

2.2. General Procedure for the Synthesis of 2-Styryl-benzimidazole Derivatives from 2-Methylbenzimidazolesand Aromatic Aldehydes. An intimate mixture of 2-methylbenzimidazole 4(a-b) (1.32 g, 10mM) was dissolvedin 10mL of glycerol in a 100mL round bottom flask. Tothis, triacetylborate (0.2 g, 10mol%) was added, followedby the addition of corresponding aromatic aldehydes 5(a-i)(10mM) and allowed it to boil at 160–180∘C in oil-bathfor 3 h using Dean-Stark apparatus. The completion of thereaction was monitored by checking TLC. At the end of thisperiod, the reaction mixture was poured into ice cold waterand the pH of the solution was adjusted to 8.0–10.0. Filterthe compound and recrystallize it by using a suitable solvent.

2.2.1. (E)-2-(2-(Benzo[d][1,3]dioxol-5-yl)vinyl)-1H-benzimid-azole (3f). Wheatish light brown crystals, Yield (2.2 g, 85%),m.p 200–204∘C, IR (KBr, ]max in cm−1): 3435 (–NH), 2922(=C–H), 1683 (C=N), 1620 (C=C), 1H NMR (DMSO-𝑑

6,

400MHz) 𝛿 ppm: 2.5 (s, 2H, –CH2), 7.2–7.4 (d, 1H, –C=CH,

JH-H = 16.4Hz), 7.5–7.3 (m, 4 aryl, 3 phenyl protons), 7.8–8.0 (d, 1H, –CH=C, JH-H = 16.4Hz), 10.0 (s, 1H, –NH ofbenzimidazole), 13C NMR (DMSO-𝑑

6, 100MHz) 𝛿 ppm:

102.29, 108.54, 109, 122, 124, 128, 130, 132, 134, 138, 148, 152 (1dioxymethylene carbon, 6 aryl carbons, 6 phenylic carbons,2 vinylic carbons and 1 imidazole quaternary carbon), MS(𝑚/𝑧): 265.10 (M+∙), Anal. Calcd. for C

16H12N2O2: C, 72.72;

H, 4.58; N, 10.60; O, 12.11% Found: C, 72.84; H, 4.70; N, 10.68;O, 12.25%.

2.2.2. (E)-2-(2-(Furan-2-yl)vinyl)-1H-benzimidazole (3g).Brown crystals, Yield (1.97 g, 94%), m.p 218–220∘C, IR (KBr,]max in cm−1): 3405 (–NH), 3101 (=C–H), 1894 (C=N), 1633(C=C), 1H NMR (DMSO-𝑑

6, 400MHz) 𝛿 ppm: 6.91–6.95

(d, 1H, –C=CH (vinylic proton), JH-H = 16.4Hz), 7.16–7.18(t, 1H, furan proton), 7.23–7.28 (q, 2H, phenylic protons),7.44–7.45 (d, 1H, furan proton), 7.57–7.61 (q, 2H, phenylicprotons), 7.67-7.68 (d, 1H, furan proton), 7.92-7.96 (d, 1H,

Organic Chemistry International 3

–CH=C–(vinylic proton), JH-H = 16.4Hz), 10.0 (s, 1H, –NHof benzimidazole), 13C NMR (DMSO-𝑑


114.47, 114.50, 122.87, 127.96, 128.51, 129.15, 129.48, 137.39,140.33, 149.87 (6 aryl carbons, 4 furyl carbons, 2 vinyliccarbons and 1 imidazole quaternary carbon), MS (𝑚/𝑧):211.10 (M+∙), Anal. Calcd. for C

13H10N2O: C, 74.27; H, 4.79;

N, 13.33; O, 7.61% Found: C, 74.34; H, 4.84; N, 13.60; O, 7.73%.

2.2.3. (E)-2-(2-(Thiophen-2-yl)vinyl)-1H-benzimidazole (3h).Light green crystals, Yield (1.97 g, 92%), m.p 198–200∘C, IR(KBr, ]max in cm−1): 3405 (–NH), 3101 (=C–H), 1894 (C=N),1633 (C=C), 1H NMR (DMSO-𝑑

6, 400MHz) 𝛿 ppm: 6.91–

6.95 (d, 1H, –C=CH (vinylic proton), JH-H = 16.4Hz), 7.16–7.18 (t, 1H, thiophenyl proton), 7.23–7.28 (q, 2H, phenylicprotons), 7.44-7.45 (d, 1H, thiophenyl proton), 7.57–7.61 (q,2H, phenylic protons), 7.67–7.68 (d, 1H, thiophenyl proton),7.92–7.96 (d, 1H, –CH=C–(vinylic proton), JH-H = 16.4Hz),10.0 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-𝑑

6,

100MHz) 𝛿 ppm: 114.47, 114.50, 122.87, 127.96, 128.51, 129.15,129.48, 137.39, 140.33, 149.87 (6 aryl carbons, 4 thiophenylcarbons, 2 vinylic carbons and 1 imidazole quaternary car-bon), MS (𝑚/𝑧): 227.07 (M+∙), Anal. Calcd. for C

13H10N2S:

C, 69.00; H, 4.45; N, 12.38; S, 14.17% Found: C, 69.24; H, 4.52;N, 12.40; S, 14.27%.

2.2.4. (E)-Phenyl(2-styryl-1H-benzimidazol-6-yl)methanone(3i). Light orange crystals, Yield (2.9 g, 90%), m.p 202–204∘C, IR (KBr, ]max in cm−1): 3401 (–NH), 2956 (=C–H),1891 (C=N), 1610 (C=C), 1644 (C=O), 1H NMR (DMSO-𝑑

6,

400MHz) 𝛿 ppm: 7.33–7.37 (d, 1H, –C=CH, vinylic proton,JH-H = 16.4Hz), 7.48–7.67 (m, 8 aryl, 5 phenyl), 10.2 (s, 1H,–NH of benzimidazole), 13C NMR (DMSO-𝑑

6, 100MHz)

𝛿 ppm: 102, 106, 108, 110, 112, 120, 121, 122, 128, 129, 130,132, 142, 148, 152, 190 (12 aryl carbons, 6 phenyl carbons, 2vinylic carbons, 1 imidazole quaternary carbon and 1 carbonylcarbon),MS (𝑚/𝑧): 325.2 (M+∙), Anal. Calcd. for C

22H16N2O:

C, 81.46; H, 4.97; N, 8.64; O, 4.93% Found: C, 81.54; H, 4.99;N, 8.76; O, 4.97%.

2.2.5. (E)-(2-(4-Fluorostyryl)-1H-benzimidazol-6-yl)(phenyl)methanone (3j). Black crystals, Yield (1.97 g, 90%), m.p 178–180∘C, IR (KBr, ]max in cm−1): 3432 (–NH), 3178 (=C–H),1909 (C=N), 1628 (C=C), 1700 (C=O), 1H NMR (DMSO-𝑑

6,

400MHz) 𝛿 ppm: 7.09–7.13 (d, 1H, –C=CH– vinulic proton,JH-H = 16.4Hz), 7.3–7.9 (m, 8 aryl, 4 phenyl), 8.09–8.13 (d,1H, –CH=C–, vinylic proton, JH-H = 16.4Hz), 10.2 (s, 1H,–NH of benzimidazole), 13C NMR (DMSO-𝑑

6, 100MHz)

𝛿 ppm: 102.29, 106.24, 108.53, 110, 112, 120, 121, 122, 128.51,129, 130, 132, 142, 148, 152, 190.91 (12 aryl carbons, 6 phenylcarbons, 2 vinylic carbons, 1 imidazole quaternary carbonand 1 carbonyl carbon), MS (𝑚/𝑧): 343.2 (M+∙), Anal. Calcd.for C22H15FN2O: C, 77.18; H, 4.42; F, 5.55; N, 8.18; O, 4.67%

Found: C, 77.32; H, 4.69; F, 5.69; N, 8.27; O, 4.73%.

2.2.6. (E)-(2-(4-Chlorostyryl)-1H-benzimidazol-6-yl)(phenyl)methanone (3k). Brown crystals, Yield (3.2 g, 90%), m.p 130–132∘C, IR (KBr, ]max in cm−1): 3426 (–NH), 2898 (=C–H),

1909 (C=N), 1601 (C=C), 1680 (C=O), 1H NMR (DMSO-𝑑6,

400MHz) 𝛿 ppm: 7.09–7.13 (d, 1H, –C=CH– vinulic proton,JH-H = 16.4Hz), 7.3–7.9 (m, 8 aryl, 4 phenyl), 8.09–8.13 (d,1H, –CH=C–, vinylic proton, JH-H = 16.4Hz), 10.2 (s, 1H,–NH of benzimidazole), 13C NMR (DMSO-𝑑

6, 100MHz)

𝛿 ppm: 102.29, 106.24, 108.53, 110, 112, 120, 121, 122, 128.51,129, 130, 132, 142, 148, 152, 190.91 (12 aryl carbons, 6 phenylcarbons, 2 vinylic carbons, 1 imidazole quaternary carbon and1 carbonyl carbon), MS (𝑚/𝑧): 359.1 (M+∙), Anal. Calcd. forC22H15ClN2O: C, 73.64; H, 4.21; Cl, 9.88; N, 7.81; O, 4.46%

Found: C, 73.52; H, 4.39; Cl, 9.96; N, 7.87; O, 4.53%.

2.2.7. (E)-(2-(4-Nitrostyryl)-1H-benzimidazol-6-yl)(phenyl)methanone (3l). Light yellow crystals, Yield (3.2 g, 90%), m.p210–212∘C, IR (KBr, ]max in cm

−1): 3410 (–NH), 2960 (=C–H),1680 (C=N), 1620 (C=C), 1670 (C=O), 1H NMR (DMSO-𝑑

6,

400MHz) 𝛿 ppm: 7.0–8.3 (m, 8 aryl, 4 phenyl and 2 vinylicprotons, JH-H = 16.4Hz), 10.2 (s, 1H, –NH of benzimidazole),13C NMR (DMSO-𝑑

6, 100MHz) 𝛿 ppm: 102, 106, 108, 110,

112, 120, 121, 122, 128, 129, 130, 132, 142, 148, 152, 190 (12 arylcarbons, 6 phenyl carbons, 2 vinylic carbons, 1 imidazolequaternary carbon and 1 carbonyl carbon), MS (𝑚/𝑧): 370.2(M+∙), Anal. Calcd. for C

22H15N3O3: C, 71.54; H, 4.09; N,

11.38; O, 12.99% Found: C, 71.62; H, 4.29; N, 11.47; O, 13.05%.

2.2.8. (E)-(2-(4-Methylstyryl)-1H-benzimidazol-6-yl)(phenyl)methanone (3m). Black crystals, Yield (3.2 g, 90%), m.p 198–200∘C, IR (KBr, ]max in cm−1): 3420 (–NH), 3214 (=C–H),1642 (C=N), 1603 (C=C), 1616 (C=O), 1H NMR (DMSO-𝑑

6,

400MHz) 𝛿 ppm: 2.4 (s, 3H, –CH3), 7.0–8.2 (m, 8 aryl, 4

phenyl and 2 vinylic protons, JH-H = 16.4Hz), 10.0 (s, 1H, –NHof benzimidazole), 13C NMR (DMSO-𝑑


21, 102, 106, 108, 110, 112, 120, 121, 122, 128, 129, 130, 132, 142, 148,152, 190 (12 aryl carbons, 6 phenyl carbons, 2 vinylic carbons,1 imidazole quaternary carbon and 1 carbonyl carbon), MS(𝑚/𝑧): 370.2 (M+∙), Anal. Calcd. for C

22H15N3O3: C, 71.54;

H, 4.09; N, 11.38; O, 12.99% Found: C, 71.62; H, 4.29; N, 11.47;O, 13.05%.

2.2.9. (E)-(2-(2-(Benzo[d][1,3]dioxol-5-yl)vinyl)-1H-benzim-idazol-6-yl)(phenyl)methanone (3n). Dark brown crystals,Yield (3.2 g, 90%), m.p > 240∘C, IR (KBr, ]max in cm−1): 3422(–NH), 2917 (=C–H), 1644 (C=N), 1575 (C=C), 1609 (C=O),1H NMR (DMSO-𝑑

6, 400MHz) 𝛿 ppm: 2.5 (s, 2H, –CH

2),

6.2–6.26 (d, 1H, –C=CH–, vinylic proton, JH-H = 16.4Hz), 7.0–8.0 (m, 8 aryl, 4 phenyl and 1 vinylic protons, JH-H = 16.4Hz),9.8 (s, 1H, –NH of benzimidazole), 13C NMR (DMSO-𝑑

6,

100MHz) 𝛿 ppm: 114.30, 115.04, 116.96, 125.42, 128.45, 128.68,129.12, 129.30, 129.48, 129.59, 131.08, 132.22, 132.33, 133.76,134.37, 137.58, 137.64, 137.74, 195.17 (1 dioxymethylene carbon,12 aryl carbons, 6 phenylic carbons, 2 vinylic carbons, 1imidazole quaternary carbon, 1 carbonyl carbon), MS (𝑚/𝑧):370.2 (M+∙), Anal. Calcd. for C

22H15N3O3: C, 71.54; H, 4.09;

N, 11.38; O, 12.99% Found: C, 71.62; H, 4.29; N, 11.47; O,13.05%.


NH2

NH2O

HO

Ar

Ar+

R

R

Green conditions

O

O O

OO

O

CH3

CH3

H3CB

HO OHOH

HN

HNCH

C

3–5h, 160–180∘C

2(a–h)1(a-b)

3(a–p)(R=H, NO2, −COPh)

(1a:R=H)(1b:R=−COPh)

Scheme 1: Synthesis of 2-styrylbenzimidazoles 3(a–p) from 1(a-b) and 2(a–h).

CH3 H

HN

N

ArR H

N

HNCH

C

OAr+

RGreen conditions

O

O OOO

O

CH3

CH3

H3CB

HO OHOH

150–160∘C

5(a–h)4(a-b)

3(a–p)(R=H, −COPh)

(4a R=H)(4b R=−COPh)

5-6h,

Scheme 2: Synthesis of 2-styrylbenzimidazoles 3(a–p) from 4(a-b) and 5(a–h).

2.2.10. (E)-(2-(2-(Furan-2-yl)vinyl)-1H-benzimidazol-6-yl)(phenyl)methanone (3o). Black crystals, Yield (3.2 g, 90%),m.p 100–102∘C, IR (KBr, ]max in cm−1): 3423 (–NH), 2921(=C–H), 1642 (C=N), 1597 (C=C), 1617 (C=O), 1H NMR(DMSO-𝑑

6, 400MHz) 𝛿 ppm: 6.6–8.1 (m, 8 aryl, 3 furanyl

and 2 vinylic protons, JH-H = 16.4Hz), 10.2 (s, 1H, –NH ofbenzimidazole), 13C NMR (DMSO-𝑑

6, 100MHz) 𝛿 ppm: 111,

112, 118, 125.12, 128.45, 128.68, 128.91, 129.47, 130.43, 131.85,132.27, 137.75, 139.96, 152.32, 195.27 (12 aryl carbons, 4 furanylcarbons, 2 vinylic carbons, 1 imidazole quaternary carbonand 1 carbonyl carbon), MS (𝑚/𝑧): 370.2 (M+∙), Anal. Calcd.for C22H15N3O3: C, 71.54; H, 4.09; N, 11.38; O, 12.99% Found:

C, 71.62; H, 4.29; N, 11.47; O, 13.05%.

2.2.11. (E)-Phenyl(2-(2-(thiophen-2-yl)vinyl)-1H-benzimid-azol-6-yl)methanone (3p). Light green crystals, Yield (3.2 g,90%), m.p 108–110∘C, IR (KBr, ]max in cm−1): 3427 (–NH),3060 (=C–H), 1633 (C=N), 1597 (C=C), 1614 (C=O), 1HNMR (DMSO-𝑑

6, 400MHz) 𝛿 ppm: 6.6–8.1 (m, 8 aryl, 3

thiophenyl and 2 vinylic protons, JH-H = 16.4Hz), 10.2 (s, 1H,–NH of benzimidazole), 13C NMR (DMSO-𝑑

6, 100MHz) 𝛿

ppm: 111, 112, 118, 125.12, 128.45, 128.68, 128.91, 129.47, 130.43,131.85, 132.27, 137.75, 139.96, 152.32, 195.27 (12 aryl carbons, 4thiophenyl carbons, 2 vinylic carbons, 1 imidazole quaternarycarbon and 1 carbonyl carbon), MS (𝑚/𝑧): 370.2 (M+∙), Anal.Calcd. for C

22H15N3O3: C, 71.54; H, 4.09; N, 11.38; O, 12.99%

Found: C, 71.62; H, 4.29; N, 11.47; O, 13.05%.


Table 1: Synthesis of 2-(2-(4-chloro-phenyl)-vinyl)-1-H-benzimidazoles.

Entry Triacetylborate (mol-%) glycerol∗ used (+)not used (−) Solvents used Time (h) Yield (%)

1. — − — 05 502. — + Glycerol 05 503. 2 − — 05 604. 5 − — 05 685. 10 − — 05 706. 2 + Glycerol 05 607. 5 + Glycerol 05 788.# 10# +# Glycerol# 05# 90#

9. 20 + Glycerol 05 8410. 20 − Ethylene glycol 06 6011. 20 − PEG-600 06 0Reactions were carried out in oil bath using Dean-Stark apparatus at 160∘C (entries 2, 6, 7, 8, and 9), 120∘C (entry 11), 190∘C (entry 10), or under solvent freeconditions at 180∘C (entries 1, 3, 4, and 5).∗10mL glycerol was used in all the above reactions.

OHOH HO

CH3CH3

CH3

CH3

O

O

O

O

O BBH3C

−CH3COOH

HH

H

NC

C

OOO

OO

(vii) (viii)

(viii)

R

RR

R

Ar

Ar

ArAr

Ar

Ar Ar

(ix)

(3)

(4)

(5)

+ HO OH

CH2

−CH3COOH

−CH3COOH

OH

OH

OH

OH

HO

HO

HO

HOHO

HO HOCH3O O

O OB

B

BB

H3O

H

H H

H

N

HN

HNN

H HH

HH

HHH

NHN

NC

O

O

OO

O O

O

OOO

O

R

+

+

+

+

+

+

+

HO

HO

−Glycerol

∙∙

∙∙∙∙

−

Scheme 3: Plausible mechanism for the formation of 2-styrylbenzimidazoles (3) from (4) and arylaldehyde (5) using glycerol andtriacetylborate.

3. Results and Discussion

In continuation of our earlier strategies for the establishmentof 2-styryl-benzimidazoles using green solvents like ethyleneglycol [10], now we have developed a highly efficient andsimple green methodology for the synthesis of 2-styryl-benzimidazole derivatives 3(a–p), by direct condensation of

equivalent amounts of substituted 𝑜-phenylenediamines 1(a-b) with various cinnamic acids 2(a–h) using 10–20mol % oftriacetylborate and glycerol (10mL) as reaction medium at160–180∘C for 3–5 h (Scheme 1).

In an alternative approach, 2-methylbenzimidazoles 4(a-b) were condensed with a variety of aromatic aldehydes5(a–h) using glycerol (10mL) as solvent and triacetylborate


Table 2: Synthesis of 2-hetero/styryl-benzimidazoles 3(a–p) from cinnamic acids 2(a–h) and benzaldehydes 5(a–h).

S.number Product 3(a–p) Method-1 (diamine + cinnamic acid) Method-2 (2-MeBz + aldehydes) M.P (∘C)

Time(h)

Temp(∘C)

Yield(%)

Time(h)

Temp(∘C)

Yield(%)

1.

HN

N4 160 90 6 160 88 205 (202) [16]

2.

HNN F

3.5 150 86 6 160 92 114-115 (113) [15]

3.

HN

N Cl3.5 160 90 6 160 90 221–223 (223-224)

[16]

4.

HNN NO2

4 150 90 6 160 92 >240 (262-263) [16]

5.

HNN CH3

5 160 85 6 160 88 210–212 (214–216)[16]

6.

HNN

OO 5 160 78 6 150 85 200–204

7. N

HN

O5 150 92 5 150 94 218–220

8. N

HN

S5 160 92 5 150 90 198–200

9.N

HN

O

5 160 90 6 160 88 202–204

10.N

HN

F

O

5 160 84 6 160 90 178–180

11.ClN

HN

O

5 160 90 6 160 90 130–132

12.N

HN

NO2

O

5 150 92 6 160 86 210–212

13.N

HN

CH3

O

5 150 88 6 160 86 198–200


Table 2: Continued.

S.number Product 3(a–p) Method-1 (diamine + cinnamic acid) Method-2 (2-MeBz + aldehydes) M.P (∘C)

Time(h)

Temp(∘C)

Yield(%)

Time(h)

Temp(∘C)

Yield(%)

14.N

HN

OO

O

5 160 84 5 160 88 >240

15.N

HN

O

O

5 160 80 5 150 82 100–102

16.N

HN

S

O

5 150 78 5 150 80 108–110

−CH3COOH−CH3COOH

−CH3COOH

OHOH

OHOH

OH

OH

OHHO

HO

CH3

CH3

CH3 CH3CH3

CH3

CH3

O O

O

O

O OO

OO

O O

O

O

OO

O

OO

OOOO

O

O

BB

B

B B B

B

B

−

HN H

NHN

O

OO

O OO

O

OO

(vii)(viii)

Ar

Ar

Ar

Ar

Ar

ArAr(4)

+

+

OH

OH

OH

OH

OHOH

OH

HO

HO

HO

H

H H

H

N

N NR

R

R

R R

(3)

(1)

NH2

NH2

NH2NH2

−H2O

+

+

+

+

+

OOCCH 3

(x)

∙∙

∙∙

∙∙

∙∙

∙∙

∙∙

Scheme 4: The alternative proposed mechanism for the formation of (3) from (1) and (4) using glycerol and triacetylborate.

(10–20mol %) at 150–180∘C for 5-6 h resulted 2-styryl-benzimidazole derivatives 3(a–p) (Scheme 2). The mostimportant advantages of our method are as follows: (a)it is totally green procedure that involves homogeneouscatalysis; (b) only 10–20mol % of triacetylborate is sufficientto complete the reaction; (c) the very simple workup doesnot involve the use of any acids; (d) the products, which in

general possess stable high melting points, solidify readilyand hence can be very easily collected and recrystallized fromsuitable solventwithout need for further purification; (e) usedtriacetylborate is cheap and readily available; (f) the yieldsof all the products are good and the reaction procedure ishighly a general one with 100% conversion in all the cases (nostarting materials were apparent by TLC).


In order to ascertain the necessity of triacetylborate,glycerol, or both, the correct solvent and the requiredtemperature, the reaction of 4-chlorobenzaldehyde (5c) with2-methylbenzimidazole (4a) was carried out separately inglycerol alone (entry 2), without glycerol and triacetylborate,that is, solvent free manner (entry 1), only triacetylborate (2–20mol %) (entries 3, 4, and 5), or both triacetylborate andglycerol (10mL) (entries 6 to 9) or in other solvents (entries10, 11) at various temperatures (Table 1). It was found that only10mol% of triacetylborate and glycerol as reactionmedium at170∘C (Table 1, entry 8#) provided the best conditions for thesynthesis of 2-styryl type benzimidazoles in good yields. Themethod is further suitable for heteroaromatic aldehydes likefurfural, thiophene-2-carboxaldehyde, and piperonaldehyde.

Triacetylborate is prepared according to the reportedprocedure [18], which is soluble in glycerol, maintaining theoptimum acidity of the reaction medium and at the sametime it is not necessary to use acids like H

2SO4or HCl and

oxalic acid to prepare salts or to recover the product duringthe work-up process. Both triacetylborate and glycerol, beinghighly soluble in water, can be recycled after the reaction.Thewater solution obtained as the filtrate can be lyophilized toreclaim the boric acid (tested by the usual way of obtainingthe green flame of ethyl borate with ethanol without addingConc. H

2SO4) which, when dried, could be further reused for

the preparation of triacetylborate.The reaction proceeds by the formation of a solke-

tal/glycerol aldehyde acetal [19, 20] type of intermediate (ix)formed by the condensation of glycerol (viii) and aromaticaldehyde (5) in presence of triacetylborate (vii), which act asa Lewis acid, is further reacted with 2-methylbenzimidazole4(a-b), and forms 2-styryl-benzimidazole 3(a-p) by losingwater molecules. At the end glycerol as a by-product can becollected as filtrate and purified for further usage (Scheme 3).

This reaction mechanism can be explained in anotherapproach, in which triacetylborate (vii) and glycerol (viii)react together to form an intermediate by losing two acetatemolecules and combine with cinnamic acid (4), where theboron loses its third acetate molecule and accepts electronsfrom the oxygen atom of cinnamic acid and forms interme-diate (x), which is further reacts with o-pheneylenediamine(1) and undergoes intramolecular cyclisation to form the finalproduct (3) (Scheme 4).

The above reactions using triacetylborate as the reagentwas found to be general and has been extended to all otherderivatives, yielding 3(a–p). All the reactions done can besummarized in Table 2.

4. Conclusions

We have highlighted the potential of triacetylborate andglycerol for the first time as a cheap, mild, highly efficient,nontoxic, and recyclable reaction medium for the high yield-ing synthesis of 2-hetero/styryl-benzimidazoles at 160–180∘Cwith wide variations both in the aldehydes and cinnamicacids and also in the 2-methylbenzimidazoles. Thus, thisgreen approach opens an important alternative to the useof volatile organic solvents and, therefore, should be highlybeneficial to both academics and industry.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding publication of this paper.

Acknowledgments

The authors are thankful to the authorities of JawaharlalNehru Technological University, Hyderabad, for providinglaboratory facilities. The authors are also grateful to theCSIR-CDRI, Lucknow, for providing financial support inthe form of OSDD project. The authors are also thankfulto CFRD, Osmania University, Hyderabad, for providingspectral analysis.

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