CC BY-NC-ND 4.0 · SynOpen 2020; 04(04): 89-95
DOI: 10.1055/s-0040-1706391
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A Task-Specific Ionic-Liquid-Mediated Solvent-Free Protocol for Direct Access to Dimethyl Acetal Protected Benzimidazole 2-Carboxaldehydes

Barnali Deb
a  Department of Chemistry, Tripura University, Suryamaninagar, 799 022, India   Email: [email protected]
,
Ankita Chakraborty
a  Department of Chemistry, Tripura University, Suryamaninagar, 799 022, India   Email: [email protected]
,
Jewel Hossain
b  Department of Chemistry, Ram Thakur College, Agartala 799 003, India
,
a  Department of Chemistry, Tripura University, Suryamaninagar, 799 022, India   Email: [email protected]
› Author Affiliations
The authors gratefully acknowledge financial support from the Science and Engineering Research Board (SERB), Govt. of India (Project No EMR/2016/001537). The authors are also grateful to the Department of Science and Technology, Ministry of Science and Technology, India for providing the 400 MHz NMR facility under the auspices of the DST-FIST programme (No SR/FST/CSI-263/2015).
 


Abstract

A robust and straightforward protocol has been developed for the synthesis of a diverse array of dimethyl acetal protected benz­imidazole-2-carboxaldehydes by reacting various 2-amino aniline derivatives with methyl 4,4-dimethoxy-3-oxobutanoate using the task-specific­ imidazolium ionic liquid (HBIm·TFA) as a promoter for N-C/C-N annulation processes. The present protocol offers several advantages over existing protocols, such as single-step process, short reaction times, very mild reaction conditions, high yields, ease of purification, recovery and reusability of the catalyst, and scale-up of the reaction.


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In drug discovery programs and for identifying biological leads, nitrogen-containing fused heterocyclic molecules play an important role as molecular templates. Among them, benzimidazole-containing heterocycles are of importance because of their broad spectrum of biological and therapeutic potentialities,[1] making them one of the more widely investigated heterocyclic scaffolds. In addition to their biological potential, they are important intermediates in many synthetic organic and inorganic reactions,[2] in dye and polymer synthesis,[3] in fluorescence,[4] chemosensing,[5] crystal engineering,[6] and corrosion science.[7] They also act as ligands in the synthesis of transition-metal complexes of structural and biological interest.[8] Therefore, their synthesis has received considerable attention and this has led to the development of several methods for the synthesis of benzimidazoles. These include the condensation of aromatic 1,2-diamines with carboxylic acids or their derivatives, generally under harsh conditions,[3] [9] oxidative cyclocondensation[10] with aldehydes, or copper(I) catalysed coupling of o-haloacetanilides with amines or amidines,[11] while very recently we and others also developed a benzimidazole synthesis by reaction with 1,2-diaminobenzene derivatives with active methylene compounds using a range of activators.[12] [13] [14] In addition to these methods, rearrangement of quinoxalines or quinoxalone derivatives under different conditions to form benzimidazole derivatives have been documented.[14] Derivatives of benzimidazole-2-carboxaldehyde have found applications in diverse therapeutic areas,[15] as well as in chalcone preparation,[16] generation of Schiff’s bases,[17] and for the creation of a library of fused poly­heterocycles.[18] Unfortunately no straightforward synthesis of functionalized benzimidazole-2-carboxaldehydes has been reported to date. They can be synthesized via multistep pathways (such as pathways 1–5 in Scheme [1]): (1) condensation of o-phenylenediamine with tartaric acid followed by cleavage of the diol with NaIO4;[18d] [e] (2) condensation of 1,2-diaminobenzene with glycolic acid and then oxidation with MnO2;[19] (3) oxidation of 2-methyl benzimidazole with SeO2;[20] (4) direct and/or directed lithiation at the 2-position of benzimidazole followed by trapping with DMF;[21] and (5) condensation of 1,2-diamino enzene with ethyl diethyoxyacetate in Na/EtOH followed by hydrolytic cleavage.[22]

Zoom Image
Scheme 1 General strategies involved in the synthesis of benzimidazole 2-carboxaldehydes

However, despite some notable advantages of the reported methods for the synthesis of benzimidazoles and benzimidazole 2-carboxaldehydes they generally suffer from a range of drawbacks, such as the requirement for stoichiometric or excess amounts of strong oxidants, high temperatures, transition-metal catalysts or harsh reaction conditions. In the area of organic synthesis, C–C bond-cleavage reaction is a topic of interest that allows C-C/C-N bond annulation to be used to construct new molecules of interest.[23] In spite of significant advances in this field, most methods rely on transition-metal catalysis. In recent times, much attention has been focused on organic reactions promoted by ionic liquids.

As a part of our ongoing program to explore the potential of protic ionic liquids in the activation of various functional groups and subsequent organic transformations, we have already demonstrated their efficacy as bifunctional catalysts for Boc protection-deprotection of amines, cleavage of 1,3-dioxolanes and in grinding chemistry.[10a] [24] Herein, we wish to report a strategy for the direct synthesis of dimethyl acetal protected benzimidazole 2-carboxaldehydes using methyl 4,4-dimethoxy-3-oxobutanoate in the presence of 1-butyl imidazolium trifluoroacetate (HBIm·TFA) as a bifunctional catalyst (Scheme [2]).

Zoom Image
Scheme 2 Protic ionic liquid promoted synthesis of benzimidazole 2-carboxaldehyde dimethylacetals

Table 1 Screening of Catalysts for Optimisation of Reaction

Entry

Activator

Temp (°C)

Time

Yield (%)a

1

[BMIm]Brb

80

4 h

50

2

[BMIm]OHb

80

12 h

20

3

[HBIm][TFA]b

80

15 min

95

4

[HBIm][TFA]b

rt

2 h

NR

5

none

80

2 h

NR

6

[Et3NH][TFA]b

80

2 h

trace

7

SiO2-KHSO4

80

2 h

80

8

SiO2-HClO4

80

2 h

80

9

SiO2-H2SO4

80

3 h

82

10

FeCl3-SiO2

80

90 min

87

11

Nano TS 1

80

50 min

83

12

Amberlite IR120H+

80

2 h

78

13

Amberlyst 15

80

90 min

73

14

[HBIm][TFA]

80

30 min

92c

a Isolated yield on 1 mmol scale.

b 5 mol% was used.

c 10 mmol scale.

To optimize the reaction conditions, o-phenylenediamine (1a) and methyl 4,4-dimethoxy-3-oxobutanoate (2) were chosen for the model reaction under different reaction conditions. Previously we have reported[12a] that the neutral ionic liquid [BMIm]Br or basic ionic liquid [BMIm]OH (10 mol%) could be utilised as activators for the synthesis of benzimidazoles by reaction of o-phenylenediamines with β-keto esters or amides at 115–120 °C, with the reaction proceeding through formation of a seven-membered benzo­diazepinone intermediate. Unfortunately our initial attempts with these ionic liquid activators failed to produce the desired product in satisfactory yield on heating 1a with 2 at 80 °C for 4 or 12 hours, respectively (Table [1], entries 1 and 2), and further increasing the temperature did not improve the yield, probably due to decomposition of 2. However, heating the reaction mixture at 80 °C in the presence of 5 mol% of protic ionic liquid (HBIm·TFA) for 15 min produced the desired benzimidazole 2-carboxldehyde dimethyl acetal 3a in 95% yield (entry 3), although reactions at room temperature or without catalyst were not successful (entries 4 and 5). The appearance of two singlets at δ = 5.70 ppm (1H) and 3.46 ppm (6H) in the 1H NMR spectrum and at δ = 98.4 and 53.6 ppm in the 13C NMR spectra of 3a corroborated the presence of the dimethyl acetal group (see Supporting Information). A molecular ion at m/z 193 further supported the structure of 3a. We also carried out the reaction with triethyl ammonium trifluoroacetate ([Et3NH][TFA]), prepared from an equimolar mixture of triethylamine and trifluoroacetic acid under identical reaction conditions (entry 6) but no product was detected. We also screened some silica supported acidic reagents such as SiO2-KHSO4 (40 mg, 10% KHSO4),[25] SiO2-HClO4 (40 mg, 10% w/v),[26] SiO2-H2SO4 (40 mg, 10% w/v),[27] SiO2-FeCl3 (32 mg containing ca. 10% FeCl3),[12b] [28] and nano titania-silica (TS1).[29] These supported reagents also afforded 2-(1,1-dimethoxy)methyl benzimidazole (3a) in 80, 80, 82, 87, and 83% yield, respectively (entries 7–11). The reaction was also investigated using commercially available sulfonic acid resins Amberlyst-15 and Amberlite IR 120H+ (entries 12 and 13). The resin-based catalysts resulted in lower yields compared to the silica supported reagents. No reaction was observed when the model reaction was conducted using 5 mol% of neat trifluoroacetic acid (results not shown). These control experiments indicated that both a proton and imidazolium cation are essential to produce 3a in high yield.

From the results presented in Table [1], the protic ionic liquid (HBImTFA) showed the best catalytic activity for the synthesis of 3a with respect to both reaction time and yield. The reaction could also be scaled up to 10 mmol scale with very little decrease of the yield using the same mol% of ionic liquid (entry 14). It is noteworthy that the high yield of 3a indicates its stability in the mildly acidic reaction medium. Another important feature of the present protocol is the recyclability of the ionic liquid for five cycles without significant loss of catalytic efficiency (95–88%). Since most of the benzimidazole product solidified after completion of reaction, the product could be collected by filtration and the mother liquor containing the ionic liquid recycled after evaporation of solvent.

Having optimized the reaction conditions, the scope of the reaction with various o-phenylenediamines with methyl 4,4-dimethoxy-3-oxobutanoate was subsequently explored; the results are summarized in Figure [1]. A wide range of aromatic diamines with electron-withdrawing or electron-donating groups at different positions of the aromatic ring, reacted smoothly in the presence of protic ionic liquid ([HBIm]TFA) to afford benzimidazole-2-carboxaldehyde dimethyl acetals 3be and 3gl in good to excellent yields within two hours. In contrast, 4-nitro-1,2-diaminobenzene afforded a different type of benzimidazole by C–C bond cleavage due to the presence of the strongly electron-withdrawing group in the aromatic ring depleting the negative charge on the nitrogen in intermediate D (see Scheme [3] below), with methoxy-directed oxidative cleavage resulting in 6-nitro-1H-benzo[d]imidazole-2-yl acetate (3f) in 35% yield with concomitant formation of many other unidentified products. All the synthesized products 3al were characterized by spectroscopic analyses. Unfortunately, 2,3-diaminopyridine failed to give the corresponding pyrido-imidazol­e derivative; rather, it produced the seven-membered heterocycle 3m, as an inseparable mixture of tautomers, in 75% yield. A similar trend was observed in the case of 2-aminothiophenol, which yielded benzothiazepinone 3n as the sole product. Attempted reaction of 2-aminophenol yielded a mixture of unidentified products, probably due to the lower nucleophilicity of the phenolic OH group, meaning that the cyclisation step is not favourable.

Zoom Image
Figure 1 o-Phenylenediamine scope

Considering the mechanism of the reaction, we anticipated that both the imidazolium cation and N-H proton are indispensable for catalytic activity as neither the imidazolium cation (entries 1 and 2) nor proton alone (entries 6, 12 and 13) provide the optimum yield of product, but N-butyl imidazolium trifluoroacetate provided the best yield in the shortest reaction time. Thus, we speculate that dual activation of the ketone oxygen of the ketone and the oxygens of the acetal group of reagent 2 (A in Scheme [3]) by both the proton and imidazolium cation activates the ketone carbonyl, thereby making it more susceptible to nucleophilic attack by the amino group of the o-phenylenediamine.

Zoom Image
Scheme 3 Plausible mechanism for dual activation of 2 by [HBIm]TFA and catalytic cycle in the synthesis of acetal 3

The resulting imine C undergoes ring-closure onto the second amino group to form aminal D followed by hydrogen-bond-assisted C–C bond cleavage to give the benzimidazole (Scheme [3]). Although the possibility of simultaneous activation of both carbonyls of 2, leading to B, cannot be overlooked; in such a situation, the benzodiazepinone may result from attack by the two amino groups on both activated carbonyls.

1H and 13C NMR spectra were recorded with a Bruker Ascend 400 spectrometer (400 MHz for 1H and 100 MHz for 13C). Chemical shifts are reported in parts per million with tetramethylsilane internal reference, and coupling constants are reported in Hertz. Proton multiplicities are represented as s (singlet), d (doublet), dd (double doublet), t (triplet), q (quartet), and m (multiplet). Infrared spectra were recorded with a Fourier transform infrared (FT-IR, Model: Spectrum 100) spectrophotometer as KBr pellets or in thin films. The reported melting points are uncorrected. High-resolution mass spectrometric (HR-MS) data were acquired by electrospray ionization with a Q-ToF-micro quadrupole mass spectrometer.

All commercial reagents were used without further purification, unless otherwise specified. Ethyl acetate and petroleum ether (60−80 °C) were distilled before use. Column chromatography was performed on silica gel (60−120 mesh, 0.12−0.25 mm). Analytical thin-layer chromatography was performed on 0.25 mm silica gel plates with a UV254 fluorescent indicator.


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General Procedure

The requisite o-phenylenediamine (108 mg, 1 mmol) and methyl 4,4-dimethoxy-3-oxobutanoate (194 mg, 1.1 mmol) were taken in a cone-shaped (10 mL) flask equipped with a small magnetic bar. HBIm·TFA (12 mg, 0.05 mmol) was then added to the mixture, which was heated at 80 °C without solvent until the disappearance of the o-phenylenediamine (TLC). After completion of reaction, the solid mass was washed several times with water to remove the ionic liquid catalyst. Finally, the product was purified by crystallization using ethyl acetate­–hexane, and ionic liquid was recovered from the mother liquo­r. In some cases, the product was purified by column chromato­graphy over silica gel, eluting with 10–50% ethyl acetate in hexane.


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2-(Dimethoxymethyl)-1H-benzimidazole (3a)

Yield: 182 mg (95%); colourless solid; mp 180 °C.

IR (neat): 2824, 1423, 1329, 1116, 1066 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.66–7.64 (dd, J = 5.6, 3.2 Hz, 2 H), 7.30–7.28 (dd, J = 6.0, 3.2 Hz, 2 H), 5.70 (s, 1 H), 3.46 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 150.3, 137.9, 122.9, 115.6, 98.4, 53.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C10H12N2O2: 193.0977; found: 193.0959.


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2-(Dimethoxymethyl)-6-methyl-1H-benzimidazole (3b)

Yield: 187 mg (91%); thick liquid.

IR (neat): 2927, 2828, 1692, 1442, 1325, 1107, 1055 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 8 Hz, 1 H), 7.40 (s, 1 H), 7.10 (d, J = 7.6 Hz, 1 H), 5.67 (s, 1 H), 3.44 (s, 6 H), 2.47 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 150.0, 132.8, 124.4, 115.2, 98.5, 53.5, 21.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H14N2O2: 207.1134; found: 207.1011.


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2-(Dimethoxymethyl)-5,6-dimethyl-1H-benzimidazole (3c)

Yield: 209 mg (95%); colourless solid; mp 100 °C.

IR (neat): 2926, 1691, 1516, 1449, 1192, 1062 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.39 (s, 2 H), 5.66 (s, 1 H), 3.43 (s, 6 H), 2.36 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 149.4, 131.9, 115.7, 98.6, 77.0, 53.5, 20.3.

HRMS (ESI-TOF): m/z [M+H]+ calcd for C12H16N2O2: 221.1290; found: 221.1250.


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6-Chloro-2-(dimethoxymethyl)-1H-benzimidazole (3d)

Yield: 203 mg (90%); colourless solid; mp 140 °C.

IR (neat): 2920, 1421, 1321, 1105, 1055 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.63 (s, 1 H), 7.55 (s, 1 H), 7.25 (s, 1 H), 5.66 (s, 1 H), 3.46 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 151.3, 128.6, 123.6, 98.3, 77.0, 53.7.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C10H11ClN2O2: 227.0587; found: 227.0561.


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2-(Dimethoxymethyl)-1H-benzimidazole-5-carboxylic Acid (3e)

Yield: 200 mg (85%); yellowish solid; mp 70 °C.

IR (neat): 2938, 2835, 1679, 1417, 1191, 1055 cm–1.

1H NMR (400 MHz, DMSO-d 6): δ = 12.87 (s, 1 H), 12.74 (s, 1 H), 8.21 (s, 0.5 H), 8.08 (s, 0.5 H), 7.82 (s, 1 H), 7.67 (s, 0.5 H), 7.52 (s, 0.5 H), 5.65 (s, 1 H), 3.38 (s, 6 H).

13C NMR (100 MHz, DMSO-d 6): δ (two tautomers) = 168.2, 153.8, 152.9, 146.4, 142.7, 137.6, 133.9, 125.4, 124.7, 124.4, 123.1, 121.5, 119.2, 114.1, 112.0, 98.9, 55.1, 53.9.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H12N2O4: 237.0875; found: 237.0838.


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Methyl 2-(6-Nitro-1H-benzo[d]imidazole-2-yl)acetate (3f)

Yield: 83 mg (35%); orange solid; mp 130 °C.

IR (neat): 2944, 1726, 1520, 1339, 1223, 1012 cm–1.

1H NMR (400 MHz, DMSO-d 6): δ = 13.09 (bs, 1 H), 8.45 (s, 1 H), 8.10 (bs, 1 H), 7.71 (bs, 1 H), 4.11 (s, 2 H), 3.70 (s, 3 H).

13C NMR (100 MHz, DMSO-d 6): δ = 169.2, 152.8, 142.9, 139.6, 118.4, 115.1, 112.2, 108.6, 52.7, 35.5.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C10H9N3O4: 236.0671; found: 236.0830.


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1-Benzyl-2-(dimethoxymethyl)-1H-benzimidazole (3g)

Yield: 231 mg (82%); thick liquid.

IR (neat): 2938, 2832, 1607, 1457, 1334, 1198, 1062 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.83 (d, J = 7.6 Hz, 1 H), 7.31–7.15 (m, 6 H), 7.14 (d, J = 6.4 Hz, 2 H), 5.58 (s, 3 H), 3.45 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 149.6, 141.9, 136.3, 135.7, 128.5, 127.4, 126.5, 123.3, 122.2, 120.3, 110.4, 100.6, 54.6, 47.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H18N2O2: 283.1447; found: 283.1429.


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1-Butyl-2-(dimethoxymethyl)-1H-benzimidazole (3h)

Yield: 198 mg (80%); thick liquid.

IR (neat): 2956, 1462, 1421, 1334, 1203, 1063 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 7.2 Hz, 1 H), 7.39 (d, J = 7.2 Hz, 1 H), 7.32–7.24 (m, 2 H), 5.60 (s, 1 H), 4.30 (t, J = 8 Hz, 2 H), 3.47 (s, 6 H), 1.86–1.79 (m, 2 H), 1.47–1.38 (m, 2 H), 0.98 (t, J = 7.2 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 149.2, 141.9, 135.6, 123.1, 122.1, 120.3, 110.0, 100.5, 54.7, 44.1, 31.7, 20.2, 13.8.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H20N2O2: 249.1603; found: 249.1589.


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1-Hexyl-2-(dimethoxymethyl)-1H-benzimidazole (3i)

Yield: 246 mg (89%); yellowish sticky solid.

IR (neat): 2929, 1462, 1421, 1334, 1203, 1063 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.79 (dd, J = 11.6, 2.0 Hz, 1 H), 7.39 (dd, J = 5.7, 2.0 Hz, 1 H), 7.32–7.24 (m, 2 H), 5.59 (s, 1 H), 4.30 (t, J = 7.6 Hz, 2 H), 3.48 (s, 3 H), 1.88–1.80 (m, 2 H), 1.41–1.32 (m, 6 H), 0.90 (t, J = 7.2 Hz, 3 H).

13C NMR (100 MHz, DMSO-d 6): δ = 149.2, 142.0, 135.6, 123.1, 122.1, 120.4, 110.0, 100.7, 54.7, 44.3, 31.4, 29.6, 22.5, 14.0.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H24N2O2: 277.1916; found: 277.1789.


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1-Octyl-2-(dimethoxymethyl)-1H-benzimidazole (3j)

Yield: 275 mg (90%); yellowish sticky solid.

IR (neat): 2925, 1461, 1336, 1201, 1066, 965 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.80 (t, J = 6.8 Hz, 1 H), 7.40 (d, J = 7.2 Hz, 1 H), 7.33–7.26 (m, 2 H), 5.60 (s, 1 H), 4.31 (t, J = 7.6 Hz, 2 H), 3.49 (s, 3 H), 1.87–1.81 (m, 2 H), 1.38–1.29 (m, 10 H), 0.90 (t, J = 7.2 Hz, 3 H).

13C NMR (100 MHz, DMSO-d 6): δ = 149.2, 142.0, 135.7, 123.1, 122.1, 120.4, 110.0, 100.7, 54.7, 44.4, 31.8, 29.7, 29.2, 29.1, 27.0, 22.6, 14.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H28N2O2: 305.2229; found: 305.2210.


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1-Allyl-2-(dimethoxymethyl)-1H-benzimidazole (3k)

Yield: 200 mg (86%); thick liquid.

IR (neat): 2933, 2831, 1620, 1515, 1331, 1206, 1064 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.80–7.78 (m, 1 H), 7.36–7.24 (m, 3 H), 6.00–5.90 (m, 1 H), 5.57 (s, 1 H), 5.20 (d, J = 10 Hz, 1 H), 5.10 (d, J = 17.2 Hz, 1 H), 4.96 (d, J = 5.6 Hz, 2 H), 3.46 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 149.2, 142.0, 135.6, 132.4, 123.3, 122.2, 120.3, 117.3, 110.3, 100.7, 54.8, 46.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H16N2O2: 233.1290; found: 233.1302.


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2-(Dimethoxymethyl)-1-(prop-2-ynyl)-1H-benzimidazole (3l)

Yield: 212 mg (92%); thick liquid.

IR (neat): 2933, 2821, 2311, 1694, 1516, 1461, 1336, 1067 cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.80 (d, J = 7.6 Hz, 1 H), 7.55 (d, J = 8 Hz, 1 H), 7.39–7.28 (m, 2 H), 5.61 (s, 1 H), 5.16 (s, 2 H), 3.50 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 148.8, 141.8, 135.1, 123.7, 122.7, 120.4, 110.1, 100.8, 77.1, 73.1, 55.0, 33.7.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H14N2O2: 231.1134; found: 231.1045.


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(Z)-2-(Dimethoxymethyl)-1H-pyrido[2,3-b][1,4]diazepin-4(5H)-one and (Z)-4--(Dimethoxymethyl)-1H-pyrido[3,2-b][1,4]di­azepin-2(5H)-one (3m)

Yield: 176 mg (75%); yellowish solid; mp 140 °C.

IR (neat): 3118, 2932, 1669, 1619, 1460, 1103, 1044 cm–1.

1H NMR (400 MHz, DMSO-d 6): δ = 8.26–8.24 (dd, J = 6.8, 1.2 Hz, 1 H), 7.15 (t, J = 7.2 Hz, 1 H), 7.01–6.99 (dd, J = 7.6, 1.2 Hz, 1 H), 6.35 (s, 1 H), 6.18 (s, 2 H), 5.20 (s, 1 H), 3.34 (s, 6 H).

13C NMR (100 MHz, DMSO-d 6): δ = 160.0, 158.0, 142.9, 142.5, 117.9, 113.8, 111.8, 103.1, 99.8, 53.9.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H37N3O3: 236.1035; found: 236.1023.


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(Z)-2-(Dimethoxymethyl)benzo[b][1,4]thiazepin-4(5H)-one (3n)

Yield: 70%; thick liquid.

IR (neat): 3276, 2945, 1615, 1478, 1438, 1272, 1150, 1066 cm–1.

1H NMR (400 MHz, CDCl3): δ = 10.56 (s, 1 H), 7.28 (m, 2 H), 6.95 (t, J = 7.6 Hz, 2 H), 4.88 (s, 1 H), 4.81 (s, 1 H), 3.74 (s, 3 H), 3.42 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 170.8, 148.1, 135.4, 129.0, 127.3, 122.7, 117.3, 115.9, 84.9, 79.8, 55.8, 50.9.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H13NO3S: 252.0649; found: 252.1009.


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Supporting Information

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  • 7 Roque JM, Pandiyan T, Cruz J, Garcia-Ochoa E. Corros. Sci. 2008; 50: 614
    • 8a Hussain A, AlAjmi MF, Rehman MT, Khan AA, Shaikh PA, Khan RA. Molecules 2018; 23: 1232
    • 8b Sahki AF, Messaadia L, Merazig H, Chibani A, Bouraiou A, Bouacida S. Chem. Sci. 2017; 129: 21
    • 8c Chkirate K, Karrouchi K, Dege N, Sebbar NK, Ejjoummany A, Radi S, Adarsh NN, Talbaoui A, Ferbinteanu M, Essassi EM, Gracia Y. New J. Chem. 2020; 44: 2210
    • 9a Gray DN. J. Heterocycl. Chem. 1970; 7: 947
    • 9b Hudkins RL. Heterocycles 1995; 41: 1045
    • 9c Mukhopadhyay C, Ghosh S, Butcher RJ. ARKIVOC 2010; 75
    • 10a Majumdar S, Chakraborty M, Pramanik N, Maiti DK. RSC Adv. 2015; 5: 51012
    • 10b Maiti DK, Halder S, Pandit P, Chatterjee N, Joarder DD, Pramanik N, Saima Y, Patra A, Maiti PK. J. Org. Chem. 2009; 74: 8086
    • 10c Chari MA, Shobha D, Sasaki T. Tetrahedron Lett. 2011; 52: 5575
    • 10d Inamdar SM, More VK, Mandal SK. Tetrahedron Lett. 2013; 54: 579
    • 10e Sharghi H, Asemani O. Synth. Commun. 2009; 39: 860
    • 10f Wen X, El Bakali J, Deprez-Poulain R, Deprez B. Tetra­hedron Lett. 2012; 53: 2440
    • 11a Peng J, Ye M, Zong C, Hu F, Feng L, Wang X, Wang Y, Chen C. J. Org. Chem. 2011; 76: 716
    • 11b Ma D, Xie S, Xue P, Zhang X, Dong J, Jiang Y. Angew. Chem. Int. Ed. 2009; 48: 4222
    • 11c Prasenjit S, Tamminana R, Nibadita P, Md AA, Rajesh P, Tharmalingam P. J. Org. Chem. 2009; 74: 8719
    • 11d Yang D, Fu H, Hu L, Jiang Y, Zhao Y. J. Org. Chem. 2008; 73: 7841
    • 11e Evindar G, Batey RA. J. Org. Chem. 2006; 71: 1802
    • 11f Zou B, Yuan Q, Ma D. Angew. Chem. Int. Ed. 2007; 119: 2652
    • 12a Chakraborty A, Majumdar S, Maiti DK. Tetrahedron Lett. 2016; 57: 3298
    • 12b Majumdar S, Chakraborty A, Bhattacharjee S, Debnath S, Maiti DK. Tetrahedron Lett. 2016; 57: 4595
    • 13a Li Z, Dong J, Chen X, Li Q, Zhou Y, Yin S.-F. J. Org. Chem. 2015; 80: 9392
    • 13b Mayo MS, Yu X, Zhou X, Feng X, Yamamoto Y, Bao M. Org. Lett. 2014; 16: 764
  • 14 Mamedov VA. RSC Adv. 2016; 6: 42132
    • 15a Chen YL, Hedberg K, Guarino K, Retsema JA, Anderson M, Manousos M, Barrett J. J. Antibiot. 1991; 44: 870
    • 15b Villa P, Arumugam N, Almansour AI, Kumar RS, Mahalingam SM, Marrioka K, Thangamani S. Bioorg. Med. Chem. Lett. 2019; 29: 729
    • 15c Hehir S, O’Donova L, Carty MP, Aldabbagh F. Tetrahedron 2008; 64: 4196
    • 15d Plater MJ, Barnes P, McDonald LK, Wallace S, Archer N, Gelbrich T, Hortonc PN, Hursthouse MB. Org. Biomol. Chem. 2009; 7: 1633
  • 16 Davis MC, Groshens TJ. Synth. Commun. 2012; 2664
    • 17a Reddy NB, Zyryanov GV, Reddy GM, Balakrishna A, Padmaja A, Padmavathi V, Reddy CS, Garcia JR, Sravya G. J. Heterocycl. Chem. 2019; 56: 589
    • 17b Omprakash KL, Reddy KG, Pal AV. C, Reddy LM. N. Indian J. Chem., Sect. A: Inorg., Bio-inorg., Phys., Theor. 1984; 23: 89
    • 18a Manna SK, Mondal SK, Ahmed A, Mondal A, Jana A, Iqbal M, Samanta S, Ray JK. RSC Adv. 2014; 4: 2474
    • 18b Manna SK, Das T, Samanta S. ChemistrySelect 2019; 4: 8781
    • 18c Ryabukhin DS, Turdakov AN, Soldatova NS, Kompanets MO, Ivanov AY, Boyarskaya IA. Beilstein J. Org. Chem. 2019; 15: 1962
    • 18d Evans RC, Douglas P, Winscom CJ. Coord. Chem. Rev. 2006; 250: 2093
    • 18e Sivasankari G, Boobalan S, Thamizhini P, Sharmila A, Kavitha K, Archana S. J. Chem. Pharm. Res. 2018; 10: 7
    • 19a Kone A, Ouattara M, Zon D, Chany A.-C, Collet S, Sissouma D, Adjou A. World J. Pharm. Res. 2018; 7: 1589
    • 19b Ooi HC, Suschitzky H. J. Chem. Soc., Perkin Trans. 1 1982; 2871
  • 20 El-Ahwany MF, Abd El-Azim MH. M. Curr. Sci. 2018; 115: 310
    • 21a Katritzky AR, He H-Y, Long Q, Cui X, Level J, Wilcox AL. ARKIVOC 2000; (iii): 240
    • 21b Katritzky AR, Rewcastle GW, Fan WQ. J. Org. Chem. 1988; 53: 5685
  • 22 Meng L, Wang SC, Fettinger JC, Kurth MJ, Tantillo DJ. Eur. J. Org. Chem. 2009; 1578
    • 23a Sara P. Angew. Chem. Int. Ed. 2019; 58: 14044
    • 23b Jiang H, Yang J, Tang X, Li J, Wu W. J. Org. Chem. 2015; 80: 8763
    • 23c Cho SH, Kim JY, Kwak J, Chang S. Chem. Soc. Rev. 2011; 40: 5068
    • 23d Song G, Wang F, Li X. Chem. Soc. Rev. 2012; 41: 3651
    • 24a Majumdar S, De J, Chakraborty A, Maiti DK. RSC Adv. 2014; 4: 24544
    • 24b Majumdar S, De J, Chakraborty A, Roy D, Maiti DK. RSC Adv. 2015; 5: 3200
    • 24c Majumdar S, Chakraborty M, Maiti DK, Chowdhury S, Hossain J. RSC Adv. 2014; 4: 16497
  • 25 Das RN, Sarma K, Pathak MG, Goswami A. Synlett 2010; 2908
  • 26 Kumar R, Kumar D, Chakraborty AK. Synthesis 2007; 299
  • 27 Azizian J, Karimi AR, Kazemizadeh Z, Mohammadi AA, Mohammadizadeh MR. Synthesis 2005; 1095
    • 28a Nasrollahzadeh M, Bayat Y, Habibi D, Moshaee S. Tetrahedron Lett. 2009; 50: 4435
    • 29a Wilde N, Pelz M, Gebhardt SG, Gläser R. Green Chem. 2015; 17: 3378
    • 29b Zhang T, Zuo Y, Liu M, Song C, Guo X. ACS Omega 2016; 1: 1034

Corresponding Author

Swapan Majumdar
Department of Chemistry, Tripura University
Suryamaninagar, 799 022
India   

Publication History

Received: 15 September 2020

Accepted after revision: 30 September 2020

Publication Date:
26 October 2020 (online)

© 2020. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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    • 8b Sahki AF, Messaadia L, Merazig H, Chibani A, Bouraiou A, Bouacida S. Chem. Sci. 2017; 129: 21
    • 8c Chkirate K, Karrouchi K, Dege N, Sebbar NK, Ejjoummany A, Radi S, Adarsh NN, Talbaoui A, Ferbinteanu M, Essassi EM, Gracia Y. New J. Chem. 2020; 44: 2210
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    • 9c Mukhopadhyay C, Ghosh S, Butcher RJ. ARKIVOC 2010; 75
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    • 10b Maiti DK, Halder S, Pandit P, Chatterjee N, Joarder DD, Pramanik N, Saima Y, Patra A, Maiti PK. J. Org. Chem. 2009; 74: 8086
    • 10c Chari MA, Shobha D, Sasaki T. Tetrahedron Lett. 2011; 52: 5575
    • 10d Inamdar SM, More VK, Mandal SK. Tetrahedron Lett. 2013; 54: 579
    • 10e Sharghi H, Asemani O. Synth. Commun. 2009; 39: 860
    • 10f Wen X, El Bakali J, Deprez-Poulain R, Deprez B. Tetra­hedron Lett. 2012; 53: 2440
    • 11a Peng J, Ye M, Zong C, Hu F, Feng L, Wang X, Wang Y, Chen C. J. Org. Chem. 2011; 76: 716
    • 11b Ma D, Xie S, Xue P, Zhang X, Dong J, Jiang Y. Angew. Chem. Int. Ed. 2009; 48: 4222
    • 11c Prasenjit S, Tamminana R, Nibadita P, Md AA, Rajesh P, Tharmalingam P. J. Org. Chem. 2009; 74: 8719
    • 11d Yang D, Fu H, Hu L, Jiang Y, Zhao Y. J. Org. Chem. 2008; 73: 7841
    • 11e Evindar G, Batey RA. J. Org. Chem. 2006; 71: 1802
    • 11f Zou B, Yuan Q, Ma D. Angew. Chem. Int. Ed. 2007; 119: 2652
    • 12a Chakraborty A, Majumdar S, Maiti DK. Tetrahedron Lett. 2016; 57: 3298
    • 12b Majumdar S, Chakraborty A, Bhattacharjee S, Debnath S, Maiti DK. Tetrahedron Lett. 2016; 57: 4595
    • 13a Li Z, Dong J, Chen X, Li Q, Zhou Y, Yin S.-F. J. Org. Chem. 2015; 80: 9392
    • 13b Mayo MS, Yu X, Zhou X, Feng X, Yamamoto Y, Bao M. Org. Lett. 2014; 16: 764
  • 14 Mamedov VA. RSC Adv. 2016; 6: 42132
    • 15a Chen YL, Hedberg K, Guarino K, Retsema JA, Anderson M, Manousos M, Barrett J. J. Antibiot. 1991; 44: 870
    • 15b Villa P, Arumugam N, Almansour AI, Kumar RS, Mahalingam SM, Marrioka K, Thangamani S. Bioorg. Med. Chem. Lett. 2019; 29: 729
    • 15c Hehir S, O’Donova L, Carty MP, Aldabbagh F. Tetrahedron 2008; 64: 4196
    • 15d Plater MJ, Barnes P, McDonald LK, Wallace S, Archer N, Gelbrich T, Hortonc PN, Hursthouse MB. Org. Biomol. Chem. 2009; 7: 1633
  • 16 Davis MC, Groshens TJ. Synth. Commun. 2012; 2664
    • 17a Reddy NB, Zyryanov GV, Reddy GM, Balakrishna A, Padmaja A, Padmavathi V, Reddy CS, Garcia JR, Sravya G. J. Heterocycl. Chem. 2019; 56: 589
    • 17b Omprakash KL, Reddy KG, Pal AV. C, Reddy LM. N. Indian J. Chem., Sect. A: Inorg., Bio-inorg., Phys., Theor. 1984; 23: 89
    • 18a Manna SK, Mondal SK, Ahmed A, Mondal A, Jana A, Iqbal M, Samanta S, Ray JK. RSC Adv. 2014; 4: 2474
    • 18b Manna SK, Das T, Samanta S. ChemistrySelect 2019; 4: 8781
    • 18c Ryabukhin DS, Turdakov AN, Soldatova NS, Kompanets MO, Ivanov AY, Boyarskaya IA. Beilstein J. Org. Chem. 2019; 15: 1962
    • 18d Evans RC, Douglas P, Winscom CJ. Coord. Chem. Rev. 2006; 250: 2093
    • 18e Sivasankari G, Boobalan S, Thamizhini P, Sharmila A, Kavitha K, Archana S. J. Chem. Pharm. Res. 2018; 10: 7
    • 19a Kone A, Ouattara M, Zon D, Chany A.-C, Collet S, Sissouma D, Adjou A. World J. Pharm. Res. 2018; 7: 1589
    • 19b Ooi HC, Suschitzky H. J. Chem. Soc., Perkin Trans. 1 1982; 2871
  • 20 El-Ahwany MF, Abd El-Azim MH. M. Curr. Sci. 2018; 115: 310
    • 21a Katritzky AR, He H-Y, Long Q, Cui X, Level J, Wilcox AL. ARKIVOC 2000; (iii): 240
    • 21b Katritzky AR, Rewcastle GW, Fan WQ. J. Org. Chem. 1988; 53: 5685
  • 22 Meng L, Wang SC, Fettinger JC, Kurth MJ, Tantillo DJ. Eur. J. Org. Chem. 2009; 1578
    • 23a Sara P. Angew. Chem. Int. Ed. 2019; 58: 14044
    • 23b Jiang H, Yang J, Tang X, Li J, Wu W. J. Org. Chem. 2015; 80: 8763
    • 23c Cho SH, Kim JY, Kwak J, Chang S. Chem. Soc. Rev. 2011; 40: 5068
    • 23d Song G, Wang F, Li X. Chem. Soc. Rev. 2012; 41: 3651
    • 24a Majumdar S, De J, Chakraborty A, Maiti DK. RSC Adv. 2014; 4: 24544
    • 24b Majumdar S, De J, Chakraborty A, Roy D, Maiti DK. RSC Adv. 2015; 5: 3200
    • 24c Majumdar S, Chakraborty M, Maiti DK, Chowdhury S, Hossain J. RSC Adv. 2014; 4: 16497
  • 25 Das RN, Sarma K, Pathak MG, Goswami A. Synlett 2010; 2908
  • 26 Kumar R, Kumar D, Chakraborty AK. Synthesis 2007; 299
  • 27 Azizian J, Karimi AR, Kazemizadeh Z, Mohammadi AA, Mohammadizadeh MR. Synthesis 2005; 1095
    • 28a Nasrollahzadeh M, Bayat Y, Habibi D, Moshaee S. Tetrahedron Lett. 2009; 50: 4435
    • 29a Wilde N, Pelz M, Gebhardt SG, Gläser R. Green Chem. 2015; 17: 3378
    • 29b Zhang T, Zuo Y, Liu M, Song C, Guo X. ACS Omega 2016; 1: 1034

Zoom Image
Scheme 1 General strategies involved in the synthesis of benzimidazole 2-carboxaldehydes
Zoom Image
Scheme 2 Protic ionic liquid promoted synthesis of benzimidazole 2-carboxaldehyde dimethylacetals
Zoom Image
Figure 1 o-Phenylenediamine scope
Zoom Image
Scheme 3 Plausible mechanism for dual activation of 2 by [HBIm]TFA and catalytic cycle in the synthesis of acetal 3