Trichloroacetimidate-Triggered Expeditious and Novel Synthesis of N-Acylbenzotriazoles

This manuscript is dedicated to Prof. (em). Richard R. Schmidt for his notable contribution on imidate chemistry

Abstract

A facile route for the synthesis of a diverse range of N-acylbenzotriazole derivatives from the corresponding carboxylic acids has been established through a carbonyl activation pathway. In this method, trichloroacetonitrile is performed as an effective reagent for an easy access of N-acylbenzotriazoles which was simply proceeded through the activation of carboxylic acids via in situ imidate formation in anhydrous 1,2-dichloroethane followed by addition of 1H-benzotriazole at 80 °C for 3–4 h. Easy handling, one-pot, and metal-free conditions demonstrate the notable merits of the devised protocol.

Keywords

N-acylbenzotriazole - benzotriazole - coupling reaction - imidate - trichloroacetonitrile

The benzotriazole methodology successfully offers a versatile synthetic protocol in organic synthesis for the rapid construction of a diverse range of molecular architectures having robust applications in chemistry, biology, and material science.[1] [2] The notable advantages, such as the nontoxic, inexpensive, and high stability nature of benzotriazole make it a useful synthetic auxiliary. Toward this end, numerous benzotriazole-based reagents, ligands, and intermediates have received attention in several organic transformations, mainly because of their special chemical behavior during the course of reaction.[3–5] Various reports have been documented for the synthesis of esters and amides,[6] thioesters,[7] acyl azides,[8] peptides,[9] diketones,[10] β-ketonitriles,[11] sulfones,[12] oxazolines, and thiazolines,[13] using N-acylbenzotriazoles through N-, O-, S-, and C-acylations under ambient conditions.[14] Furthermore, benzotriazole ring cleavage (BtRC) methodology enables the synthesis of N-phenylamides,[15] benzoxazoles,[16] and benzothiazoles,[17] significantly by utilizing the respective N-acylbenzotriazoles. In addition, carbamates, ureas, and thiocarbamates have been successfully prepared through Curtius rearrangement in good-to-excellent yields.[18] Therefore, development of novel and common routes for an easy access of N-acylbenzotriazoles is a highly promising area.

The formation of N-acylbenzotriazoles involves the key transformation of carboxylic acids in organic synthesis. Therefore, efforts have been devoted to develop robust protocols for easy access to N-acylbenzotriazoles (Scheme [1]). The approaches are commonly characterized by two archetypal pathways. The first involves carbonyl activation (where BtH is added to activated carboxylate), which mainly comprises activators such as I₂/PPh₃, NBS/PPh₃, or TCT/PPh₃;[19] [20] [21] [22] EDC or DCC[23] along with tosyl chloride[24] and BtH with or without base. Alternatively, activation of benzotriazole involves a carboxylic acid being added to the activated BtH. Surprisingly, very few reports are available for the BtH activation process. For example, 1-(methane sulfonyl)benzotriazole has been shown to be electrophilic enough to react with carboxylic acids in the presence of Et₃N,[25a] and the reaction of thionyl chloride with BtH (3–4 equiv.) accomplished the acylation of benzotriazole.[25b] Investigations of suitable reagents that proceed through BtH activation has received less attention because of the side products generated from the loss of the leaving group are reactive towards sensitive functionalities. Moreover, the carbonyl activation pathway has been explored, mainly because this process avoids the use of strong acids and bases which makes the transformation more convenient and practical. We have recently reported a new approach using 2,2′-dipyridyl disulfide/PPh₃ [26] and further extended this with the aid of TCICA/PPh₃ [27] for easy access to diverse N-acylbenzotriazoles from the corresponding acids through a carbonyl activation pathway in high-to-excellent yields. In the context of carbonyl activation, a report is well documented for the conversion of carboxylic acids into respective amides (via acid chloride formation) using the combination of the activators trichloroacetonitrile (TCA) and PPh_3. [28] However, the disclosed protocol was limited to the synthesis of benzamides, rather than acylation of benzotriazole.[28]

Scheme 1 Established tactics for synthesis of N-acylbenzotriazoles from the corresponding carboxylic acids.

Functionalization of various groups via imidate formation is well known, and they are the important class of intermediates to introduce different groups,[29] as well as acting as a directing group.[30] Different imidate-based complexes of gold[31] and palladium[32] are also known for use in catalysis. Among which, trichloroacetimidates are known to be powerful leaving groups in glycoscience[33] [34] [35] [36] and have been extensively explored as glycosyl donors in glycosylation reactions with various acceptors in the presence of a suitable promoter.[37] Numerous reports have demonstrated the formation of O/N-glycosides with glycosyl trichloroacetimidates that do not require the addition of a promoter.[38]

Thus, in continuation of our previous studies into N-acylbenzotriazole synthesis, we have continued investigating the activation of carboxylic acids via trichloroacetimidates and have established that these act as effective reagents for easy access to N-acylbenzotriazoles, the results of which we wish to report herein.

Table 1 Reaction Optimization Study for N-Acylbenzotriazole Synthesis via Trichloroacetimidate Intermediates

Entrya	CCl3CN (equiv.)	Temp (°C)	Base (equiv.)	Solventb	Time (h)	Yield (%)c
1	1.0	60	DMAP (0.5)	DCM	2	45
2	1.0	80	DMAP (1.0)	DCM	3	50
3	1.0	80	DMAP (1.0)	DCE	3	58
4	2.0	80	DMAP (1.0)	DCE	3	80
5	4.0	80	DMAP (1.0)	DCE	3	78
6	–	80	DMAP (1.0)	DCE	3	NIL
7	2.0	80	DMAP (1.0)	toluene	3	70
8	2.0	80	DMAP (1.0)	DMF	3	45
9	2.0	80	DMAP (1.0)	CHCl3	3	52
10	2.0	80	DMAP (1.0)	H2O	8	NIL
11	2.0	80	Et3N (1.0)	DCE	3	42
12	2.0	80	DBU (1.0)	DCE	3	70
13	2.0	80	K2CO3 (1.0)	DCE	3	48
14	2.0	80	–	DCE	3	40
15	2.0	r.t	DMAP (1.0)	DCE	3	trace
16	2.0	120	DMAP (1.0)	DCE	3	78
17	2.0	150	DMAP (1.0)	DCE	3	72

^a Reactions carried out at reflux under argon atmosphere.

^b Dry solvents were used.

^c Yields reported after column chromatography (SiO₂).

Our investigation commenced with a model reaction of 1-naphthoic acid (1.0 equiv.) with trichloroacetonitrile (CCl₃CN, 1.0 equiv.) and 4-dimethylaminopyridine (DMAP, 0.5 equiv.) in dichloromethane (DCM) at 60 °C for 2.0 h to afford (1H-benzo[d][1,2,3]triazol-1-yl)(napthalen-1-yl)methanone (2q) in moderate yield (Table [1], entry 1). After establishing CCl₃CN as suitable reagent, we proceeded to improve the reaction yield. The types of base and CCl₃CN in various ratios and solvents were investigated at different temperatures and for the different time intervals. The yield was seen to be enhanced when 1.0 equivalent of base is used at 80 °C for 3 h under the established reaction conditions (Table [1], entry 2). In continuation, the conversion was improved when the molar ratio of CCl₃CN was doubled at 80 °C for 3 h in DCE, resulting in 80% yield of compound 2q (Table [1], entry 4). Increasing the amount of CCl₃CN up to 4.0 equivalents did not result in a better outcome in terms of reaction yield (Table [1] entry 5). However, no product was detected when the reaction was carried without CCl₃CN (Table [1], entry 6), confirming that CCl₃CN is essential. Towards optimization, we examined the reaction by varying the solvents such as toluene, CHCl₃, and DMF (Table [1], entries 7–9), although these were found to be less efficient than DCE. Water was also taken examined, but no conversion was observed (Table [1], entry 10). Different bases such as Et₃N, DBU, and K₂CO₃ were considered, but no reasonable improvement in the yield was detected. Among these only DBU was found to be efficient, which showed approximately the same result as DMAP (Table [1], entry 12). The reaction was also carried out without base (Table [1], entry 14), but only traces of product were detected, which confirms that base is necessary. At room temperature, low conversion was observed (Table [1], entry 15), but conversion increases with increasing temperature up to 80 °C (Table [1], entry 4) and a notable reduction in yield was observed when the reaction was carried out at higher temperature (Table [1], entries 16 and 17). From the above investigations we concluded that optimal conditions involved CCl₃CN (2.0 equiv.) and DMAP (1.0 equiv.) in DCE, followed by the addition of 1H-benzotriazole at 80 °C for 3 h. Under these conditions, compound 2q was isolated in 80% yield after column chromatography (Table [1], entry 4).

Scheme 2 Molar ratios: substituted benzoic acids 1 (1.0 equiv.), CCl₃CN (2.0 equiv.), DMAP (1.0 equiv.), BtH (1.0 equiv.). Yields reported after column chromatography (SiO₂).

Subsequently the optimized protocol was applied to construct a library of diverse N-acylbenzotriazole derivatives 2a–t by incorporation of various substituents on the benzene ring of the carboxylic acids (Scheme [2]). Furthermore, we investigated the effect of substituents on the benzene ring of the carboxylic acids and found that the rings substituted with electron-withdrawing groups afforded the compounds 2i,j,k,s in slightly lower yield compared to substrates having electron-donating groups 2m,n,p.

The reaction also proceeded well with polynuclear aromatic precursors. For example, the reaction of α-naphthoic acid under the optimized conditions furnished a good yield of the respective 1H-benzo[d][1,2,3]triazol-1-yl)(napthalen-1-yl)methanone (2q). The α,β-unsaturated acid, cinnamic acid, also reacted well to afford (E)-1-{1H-benzo[d][1,2,3]triazol-1-yl}-3-phenylprop-2-en-1-one (2t) after column chromatography.

To explore the scope of the protocol, we considered the reaction with different aliphatic carboxylic acid derivatives under optimized conditions, where the respective N-acylbenzotriazoles 3a–d were isolated after column chromatography in moderate to good yields (Scheme [3]). The reaction was also carried out with short-chain aliphatic carboxylic acids such as acetic acid under optimized reaction protocol; unfortunately, no reaction was observed.

Scheme 3 Molar ratios: N-acylbenzotriazoles (1, 1.0 equiv.), CCl₃CN (2.0 equiv.), DMAP (1.0 equiv.), BtH (1.0 equiv.). Yields reported after column chromatography (SiO₂).

Trichloroacetimidate as an electrophile has been utilized for esterification reactions under mild reaction conditions.[39] This method involves activation of the alcohol,[39] rather than activation of the carboxylic acid via trichloroacetimidate as described herein.

A possible mechanism for the preparation of 2 is proposed in Scheme [4] for which carboxylic acid 1 initially reacts with trichloroacetonitrile to give the corresponding trichloroacetimidic anhydride intermediate I. Subsequent, addition of benzotriazole to the intermediate II results in formation of final product 2 with the loss of trichloroacetamide III.

Scheme 4 Proposed mechanism for the synthesis of N-acylbenzotriazole 2 via an intermediate imidate.

In conclusion, we report a facile route for the synthesis of N-acylbenzotriazole derivatives by activation of different aromatic and aliphatic carboxylic acid derivatives with trichloroacetonitrile (CCl₃CN). The reaction is proposed to proceed through the formation of the corresponding imidate intermediates leading to the formation of respective N-acylbenzotriazole derivatives. The methodology is a one-pot protocol with broad substrate scope.

All chemicals and solvents were of analytical grade. Thin-layer chromatography (TLC) was performed on 60 F254 silica gel, pre-coated on aluminium plates, and seen under a UV lamp (λ_max = 254 nm). Solvents were condensed under low pressure at temperature < 55°C. Column chromatography was subjected to silica gel (100–200 mesh, 230–400 mesh, Merck). Ethyl acetate and n-hexane were distilled before column chromatography. ¹H, ¹³C, and ¹⁹F NMR spectra were recorded at 500, 125, and 470 MHz, respectively. Chemical shifts were recorded in ppm downfield from internal TMS, J values in Hz. Mass spectra were recorded using SCIEX X500r Q-TOF, ahigh-resolution mass spectrometer (HRMS).

Typical Experimental Procedure for the Synthesis of N-Acylbenzotriazoles 2

To a solution of carboxylic acid (1.0 equiv.) 1,2 dichloroethane, trichloroacetonitrile (2.0 equiv.), and DMAP (1.0 equiv.) were added. Then, the reaction mixture was shaken for 10 min at room temperature, followed by addition of 1H-benzotriazole. The reaction was left at 80 °C for 3–4 h. After the completion of reaction (monitored by TLC), the resulting reaction mixture was evaporated under reduced pressure. The residue was subjected to column chromatography (2–10% ethyl acetate/n-hexane) to afford the desired N-acylbenzotriazoles.

Physical Data for Aromatic and Aliphatic N-Acylbenzotriazoles 2a–t and 3a–d

(1H-Benzo[d][1,2,3]triazol-1-yl)(4-chlorophenyl)methanone (2a)[27] [40]

White solid, yield 0.230 g (70%); mp 134–137 °C; R_f = 0.5 (10% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.38 (d, J = 9.0 Hz, 1 H), 8.22–8.17 (m, 3 H), 7.73–7.70 (m, 1 H), 7.57–7.55 (m, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.5, 145.7, 140.4, 133.1, 132.2, 130.5, 129.7, 128.8, 126.4, 120.2, 114.7 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2-chlorophenyl)methanone (2b)[27]

White solid, yield 0.223 g (68%); mp 80–84 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.39 (d, J = 8.0 Hz, 1 H), 8.13 (d, J = 9.5 Hz, 1 H), 7.71 (t, J = 8.0 Hz, 1 H), 7.65 (d, J = 7.0 Hz, 1 H), 7.56–7.52 (m, 3 H), 7.45–7.42 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.7, 146.1, 132.7, 132.4, 132.2, 131.1, 130.5, 130.05, 130.02, 126.6, 126.5, 120.2, 114.3 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(3-chlorophenyl)methanone (2c)[27] [40]

White solid, yield 0.230 g (70%); mp 122–123 °C. R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.40 (d, J = 8.5 Hz, 1 H), 8.20 (t, J = 8.5 Hz, 2 H), 8.13 (d, J = 7.5 Hz, 1 H), 7.75–7.72 (m, 1 H), 7.67 (d, J = 7.5 Hz, 1 H), 7.59–7.51 (m, 2 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.4, 145.8, 134.6, 133.6, 133.1, 132.2, 131.5, 130.6, 129.8, 129.7, 126.5, 120.3, 114.7 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2,3-dichlorophenyl)methanone (2d)[27]

White solid, yield 0.173 g (57%); mp 135–136 °C; R_f = 0.55 (15% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.41 (d, J = 8.0 Hz, 1 H), 8.17 (d, J = 9.0 Hz, 1 H), 7.77–7.70 (m, 2 H), 7.60–7.58 (m, 1 H), 7.53 (d, J = 6.5 Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.0, 146.2, 135.0, 134.1, 133.0, 131.1, 130.8, 130.6, 127.7, 127.5, 126.8, 120.5, 114.4 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(4-bromophenyl)methanone (2e)[27]

Off-white solid, yield 0.204 g (68%); mp 130–135 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.38 (d, J = 8.0 Hz, 1 H), 8.17–8.10 (m, 3 H), 7.73–7.69 (m, 3 H), 7.56 (t, J = 8.0 Hz, 1 H), 7.53 (d, J = 6.5 Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 166.0, 145.7, 133.4, 132.5, 132.1, 130.8, 130.4, 129.4, 126.7, 120.5, 115.0 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(3-bromophenyl)methanone (2f)[27]

White solid, yield 0.195 g (65%); mp 160–161 °C; R_f = 0.6 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.38–8.35 (m, 2 H), 8.18–8.16 (m, 2 H), 7.81 (d, J = 8.5 Hz, 1 H), 7.73–7.70 (m, 1 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.47–7.44 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.3, 145.8, 136.6, 134.4, 133.3, 132.2, 130.7, 130.3, 130.0, 126.6, 122.5, 120.3, 114.8 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2-bromophenyl)methanone (2g)[16]

White solid, yield 0.201 g (67%); R_f = 0.7 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.41 (d, J = 8.5 Hz, 1 H), 8.16 (d, J = 8.0 Hz, 1 H), 7.75–7.71 (m, 2 H), 7.62–7.55 (m, 2 H), 7.51–7.45 (m, 2 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 166.4, 146.2, 135.0, 133.2, 132.5, 131.2, 130.6, 130.0, 127.2, 126.6, 120.5, 120.3, 114.4 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2,5-dibromophenyl)methanone (2h)[18]

White solid, yield 0.163 g (60%); mp 163–165 °C; R_f = 0.5 (10% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.39 (d, J = 8.5 Hz, 1 H), 8.17 (d, J = 8.5 Hz, 1 H), 7.76–7.72 (m, 2 H), 7.60–7.57 (m, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 164.9, 146.3, 136.7, 135.4, 134.6, 132.6, 131.1, 130.8, 126.8, 121.2, 120.5, 119.1, 114.3 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(3-fluorophenyl)methanone (2i)[16] [40]

White solid, yield 0.196 g (57%); mp 100–103 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.39 (d, J = 7.5 Hz, 1 H), 8.18 (d, J = 8.5 Hz, 1 H), 8.05 (d, J = 8.5 Hz, 1 H), 7.95 (d, J = 9.5 Hz, 1 H), 7.74–7.71 (m, 1 H), 7.59–7.54 (m, 2 H), 7.42–7.39 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.4, 163.3, 161.3, 145.8, 133.4 (d, J _C–F = 31.9 Hz), 132.3, 130.7, 130.2 (d, J _C–F = 26.8 Hz), 127.6 (d, J _C–F = 10.8 Hz), 126.6, 120.8 (d, J _C–F = 81.3 Hz), 120.4, 118.8, 118.6, 114.8 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2-fluorophenyl)methanone (2j)[18]

White solid, yield 0.179 g (52%); mp 96–98 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.38 (d, J = 7.5 Hz, 1 H), 8.15 (d, J = 8.5 Hz, 1 H), 7.78 (t, J = 6.5 Hz, 1 H), 7.73–7.70 (m, 1 H), 7.65–7.61 (dd, J = 6.5, 7.0 Hz, 1 H), 7.55 (t, J = 7.5 Hz 1 H), 7.35–7.32 (m, 1 H), 7.26–7.23 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 164.2, 161.4, 159.3, 146.1, 134.5 (d, J _C–F = 31.9 Hz), 131.3 (d, J _C–F = 94.5 Hz), 130.5, 126.5, 124.2 (d, J _C–F = 8.9 Hz), 121.4 (d, J _C–F = 49.3 Hz), 120.3, 116.6, 116.4, 114.4 ppm.

3-(1H-Benzo[d][1,2,3]triazol-1-carbonyl)benzonitrile (2k)

White solid, yield 0.209 g (62%); mp ≥180 °C; R_f = 0.3 (10% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.55 (s, 1 H), 8.48 (d, J = 8.0 Hz 1 H), 8.41 (d, J = 9.5 Hz,1 H), 8.20 (d, J = 8.0 Hz 1 H), 7.97 (d, J = 8.0 Hz, 1 H), 7.77–7.72 (m, 2 H), 7.62–7.58(m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 164.6, 145.8, 136.4, 135.9, 132.7, 132.0, 130.9, 129.4, 126.8, 120.4, 117.6, 114.7, 113.1 ppm.

HRMS (ESI+): m/z [M + NH₄ ⁺] calcd for C₁₄H₁₂N₅O⁺: 266.1036; found: 266.9487.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2-iodophenyl)methanone (2l)[26] [27]

White solid, yield 0.199 g (71%); mp 80–83 °C; R_f = 0.6 (10% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.40 (d, J = 7.5 Hz, 1 H), 8.16 (d, J = 8.0 Hz, 1 H), 7.97 (d, J = 8.0 Hz, 1 H), 7.75–7.72 (m, 1 H), 7.58–7.51 (m, 3 H), 7.30–7.26 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 167.5, 146.2, 139.6, 138.8, 132.3, 131.3, 130.6, 129.8, 127.7, 126.6, 120.3, 114.4, 93.3 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(m-tolyl)methanone (2m)[16] [40]

White solid, yield 0.243 g (70%); mp 65–66 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.38 (d, J = 8.0 Hz, 1 H), 8.17 (d, J = 8.5 Hz, 1 H), 8.01 (d, J = 6.5 Hz, 2 H), 7.72–7.69 (m, 1 H), 7.56–7.53 (m, 1 H), 7.51–7.44 (m, 2 H), 2.48 (s, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 166.9, 145.7, 138.3, 134.4, 132.3, 132.0, 131.4, 130.3, 128.9, 128.2, 126.2, 120.1, 114.7, 21.3 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(3,5-dimethylphenyl)methanone (2n)[18]

White solid, yield 0.230 g (69%); mp 68–70 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.37 (d, J = 8.0 Hz, 1 H), 8.16 (d, J = 8.0 Hz, 1 H), 7.78 (s, 2 H), 7.72–7.67 (m, 1 H), 7.55–7.52 (m, 1 H), 7.31 (s, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 167.1, 145.6, 138.1, 135.4, 132.3, 131.3, 130.2, 129.2, 127.8, 126.2, 125.9, 120.0, 114.7, 21.2 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(2-methoxyphenyl)methanone (2o)[27]

White solid, yield 0.236 g (71%); mp 92–94 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.39 (d, J = 8.5 Hz, 1 H), 8.13 (d, J = 7.5 Hz, 1 H), 7.71–7.68 (m, 1 H), 7.62–7.51 (m, 3 H), 7.13–7.06 (m, 2 H), 3.77 (s, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 166.9, 157.8, 146.0, 133.5, 131.4, 130.2, 130.1, 126.1, 122.7, 120.4, 120.0, 114.4, 111.4, 55.7 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(phenyl)methanone (2p)[26]

White solid, yield 0.274 g (75%); mp 110–112 °C; R_f = 0.6 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.40 (d, J = 8.0 Hz, 1 H), 8.23–8.17 (m, 3 H), 7.73–7.68 (dd, J = 15.5, 8.0 Hz, 2 H), 7.60–7.54 (m, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 166.7, 145.7, 133.6, 132.3, 131.7, 131.4, 130.4, 128.4, 126.3, 120.1, 114.7 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(napthalen-1-yl)methanone (2q)[27]

White solid, yield 0.253 g (80%); mp 137–140 °C; R_f = 0.7 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.50 (d, J = 8.0 Hz, 1 H), 8.19–8.12 (m, 3 H), 7.98–7.94 (m, 2 H), 7.81–7.75 (m, 1 H), 7.63–7.57 (m, 4 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 167.6, 146.1, 133.5, 132.9, 132.0, 131.0, 130.4, 130.1, 129.3, 128.7, 127.9, 126.7, 126.4, 124.7, 124.2, 120.3, 114.7 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(furan-2-yl)methanone (2r)[26]

White solid, yield 0.239 g (63%); mp 168–170 °C; R_f = 0.8 (10% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.41 (d, J = 8.5 Hz, 1 H), 8.17–8.14 (m, 2 H), 7.87–7.85 (m, 1 H), 7.70–7.67 (m, 1 H), 7.55–7.52 (m, 1 H), 6.73–6.72 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 155.1, 149.0, 145.6, 144.7, 132.2, 130.6, 126.4, 124.8, 120.3, 114.8, 113.0 ppm.

(1H-Benzo[d][1,2,3]triazol-1-yl)(trifluoromethyl)phenyl)methanone (2s)[19] [27]

White solid, yield 0.150 g (49%); mp 55–58 °C; R_f = 0.7 (10% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.49 (s, 1 H), 8.44 (d, J = 7.5 Hz, 1 H), 8.38 (d, J = 9.0 Hz, 1 H), 8.17 (d, J = 8.5 Hz, 1 H), 7.95 (d, J = 7.5 Hz, 1 H), 7.74–7.71 (m, 2 H), 7.58–7.55 (m, 1 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 165.3, 145.7, 134.8, 132.1 (d, J _C–F = 87.4 Hz), 131.1 (d, J _C–F = 119.0 Hz), 130.7, 130.04 (d, J _C–F = 12.7 Hz), 129.0, 128.5 (d, J _C–F = 12.2 Hz), 126.6, 124.5, 120.3, 114.7 ppm.

(E)-1-(1H-Benzo[d][1,2,3]triazol-1-yl)-3-phenylprop-2-en-1-one (2t)[41]

White solid, yield 0.198 g (59%); mp 150–151 °C; R_f = 0.5 (50% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.43 (d, J = 8.0 Hz, 1 H), 8.16–8.15 (m, 3 H), 7.77–7.75 (m, 2 H), 7.69 (t, J = 8.0 Hz, 1 H), 7.55–7.52 (m, 1 H), 7.48–7.47 (m, 3 H) ppm,

¹³C NMR (125 MHz, CDCl₃): δ = 163.9, 148.7, 146.3, 134.1, 131.4, 130.3, 129.1, 129.0, 126.2, 120.1, 116.0, 114.8 ppm.

1-(1H-Benzo[d][1,2,3]triazol-1-yl)heptan-1-one (3a)[42]

Light yellow semisolid, yield 0.241 g (68%); R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.28 (d, J = 8.0 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 1 H), 7.63 (t, J = 8.0 Hz, 1 H), 7.50–7.47 (m, 1 H), 3.42–3.39 (m, 2 H), 1.92–1.86 (m, 2 H), 1.50–1.44 (m, 2 H), 1.38–1.31 (m, 4 H), 0.90–0.88 (m, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 172.6, 146.0, 131.0, 130.2, 125.9, 120.0, 114.3, 35.4, 31.4, 28.7, 24.3, 22.4, 13.9 ppm.

1-(1H-Benzo[d][1,2,3]triazol-1-yl)decan-1-one (3b)

Colorless oil, yield 0.199 g (63%); R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.28 (d, J = 9.0 Hz, 1 H), 8.11 (d, J = 8.0 Hz, 1 H), 7.63 (t, J = 8.0 Hz, 1 H), 7.48 (t, J = 8.0 Hz, 1 H), 3.40 (t, J = 8.0 Hz, 2 H), 1.92–1.85 (m, 2 H), 1.49–1.43 (m, 2 H), 1.39–1.25 (m, 10 H), 0.86 (t, J = 6.5 Hz, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 172.6, 146.1, 131,0, 130.2, 125.9,120.0, 114.4, 35.4, 31.8, 29.3, 29.25, 29.20, 29.0, 24.4, 22.6, 14.0 ppm.

HRMS (ESI+): m/z [M + Na] calcd for C₁₆H₂₃N₃NaO: 296.1739; found: 296.1745.

1-(1H-Benzo[d][1,2,3]triazol-1-yl)tetradecan-1-one (3c)[43]

Yellowish solid, yield 0.158 g (55%); mp 40-42 °C; R_f = 0.5 (5% ethyl acetate/n-hexane);

¹H NMR (500 MHz, CDCl₃): δ = 8.30 (d, J = 8.0 Hz, 1 H), 8.12 (d, J = 8.0 Hz, 1 H), 7.65 (t, J = 8.0 Hz, 1 H), 7.50 (t, J = 8.0 Hz, 1 H), 3.43–3.40 (m, 2 H), 1.94–1.87 (m, 2 H), 1.51–1.45 (m, 2 H), 1.39–1.25 (m, 18 H), 0.89–0.86 (m, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 172.7, 146.2, 131.1, 130.3, 126.0, 120.1, 114.4, 35.5, 31.9, 29.65, 29.62, 29.5, 29.4, 29.3, 29.2, 29.1, 29.0, 24.4, 22.6, 14.1 ppm.

1-(1H-Benzo[d][1,2,3]triazol-1-yl)hexadecan-1-one (3d)[44]

White solid, yield 0.136 g (49%); mp 48–50 °C; R_f = 0.5 (5% ethyl acetate/n-hexane).

¹H NMR (500 MHz, CDCl₃): δ = 8.30 (d, J = 8.0 Hz, 1 H), 8.12 (d, J = 8.0 Hz, 1 H), 7.66–7.63 (m, 1 H), 7.50 (t, J = 8.0 Hz, 1 H), 3.43–3.40 (m, 2 H), 1.93–1.87 (m, 2 H), 1.49–1.44 (m, 2 H), 1.40–1.25 (m, 22 H), 0.88–0.86 (m, 3 H) ppm.

¹³C NMR (125 MHz, CDCl₃): δ = 172.7, 146.1, 131.1, 130.3, 126.0, 120.1, 114.4, 35.5, 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 29.0, 24.4, 22.6, 14.1 ppm.

HRMS (ESI+): m/z [M + H] calcd for C₂₂H₃₆N₃O: 358.2858; found: 358.2875.

Conflict of Interest

The authors declare no conflict of interest.

• References

• 1 Katritzky AR, Lan X, Yang JZ, Denisko OV. Chem. Rev. 1998; 98: 409
• 2 Briguglio I, Piras S, Corona P, Gavini E, Nieddu M, Boatto G, Carta A. Eur. J. Med. Chem. 2015; 97: 612
• 3 Katritzky AR, Rachwal S. Chem. Rev. 2010; 110: 1564
• 4a Kale RR, Prasad V, Mohapatra PP, Tiwari VK. Monatsh. Chem. 2010; 141: 1159
• 4b Yu J, Singh AS, Yan G, Yu J, Tiwari VK. Synthesis 2020; 52: 3781
• 5 Singh M, Singh AS, Mishra N, Agrahari AK, Tiwari VK. ACS Omega 2019; 4: 2418
• 6a Katritzky AR, Rogovoy BV, Kirichenko N, Vvedensky V. Bioorg. Med. Chem. Lett. 2002; 12: 1809
• 6b Katritzky AR, Suzuki K, Singh SK, He H.-Y. J. Org. Chem. 2003; 68: 5720
• 6c Katritzky AR, Singh SK, Cai C, Bobrov S. J. Org. Chem. 2006; 71: 3364
• 6d Kale RR, Prasad V, Tiwari VK. Lett. Org. Chem. 2010; 7: 136
• 7a Zhou G, Lim D, Fang F, Coltart DM. Synthesis 2009; 3350
• 7b Xia Z, Lv X, Wang W, Wang X. Tetrahedron Lett. 2011; 52: 4906
• 7c Katritzky AR, Shestopalov AA, Suzuki K. Synthesis 2004; 1806
• 8 Katritzky AR, Widyan K, Kirichenko K. J. Org. Chem. 2007; 72: 5802
• 9 Gonnet Lori, Tintillier T, Venturini N, Konnert L, Hernandez J.-F, Lamaty F, Laconde G, Martinez J, Colacino E. ACS Sustainable Chem. Eng. 2017; 5: 2936
• 10a Wang X, Zhang Y. Synth. Commun. 2003; 33: 2627
• 10b Lim D, Fang F, Zhou G, Coltart DM. Org. Lett. 2007; 9: 4139
• 11 Katritzky AR, Abdel-Fattah AA. A, Wang M. J. Org. Chem. 2003; 68: 4932
• 12 Katritzky AR, Abdel-Fattah AA. A, Wang M. J. Org. Chem. 2003; 68: 1443
• 13 Katritzky AR, Cai C, Suzuki K, Singh SK. J. Org. Chem. 2004; 69: 811
• 14a Wang X, Wang W, Wen Y, He L, Zhu X. Synthesis 2008; 3223
• 14b Katritzky AR, Suzuki K, Wang Z. Synlett 2005; 1656
• 14c Li J, Sun Y, Chen Z, Su W. Synth. Commun. 2010; 40: 3669
• 15 Singh AS, Kumar D, Mishra N, Tiwari VK. ChemistrySelect 2017; 2 224
• 16 Singh AS, Mishra N, Kumar D, Tiwari VK. ACS Omega 2017; 2: 5044
• 17a Yadav MS, Singh AS, Agrahari AK, Mishra N, Tiwari VK. ACS Omega 2019; 4: 6681
• 17b Kumar D, Mishra BB, Tiwari VK. J. Org. Chem. 2014; 79: 251
• 17c Kumar D, Mishra A, Mishra BB, Bhattacharya S, Tiwari VK. J. Org. Chem. 2013; 78: 899
• 17d Singh AS, Kumar D, Tiwari VK. ChemistrySelect 2018; 3: 7809
• 17e Singh AS, Mishra N, Yadav MS, Tiwari VK. J. Heterocycl. Chem. 2019; 56: 275
• 18a Yadav MS, Singh SK, Agrahari AK, Singh AS, Tiwari VK. Synthesis 2021; 53: 2494
• 18b Singh AS, Kumar D, Mishra N, Tiwari VK. RSC Adv. 2016; 6: 84512
• 18c Singh AS, Agrahari AK, Singh SK, Yadav MS, Tiwari VK. Synthesis 2019; 51: 3443
• 19a Singh AS, Agrahari AK, Singh M, Mishra N, Tiwari VK. ARKIVOC 2017; (v): 80
• 20 Agha KA, Abo-Dya NE, Ibrahim TS, Abdel-Aal EH. ARKIVOC 2016; (iii): 161
• 21 Singh M, Agrahari AK, Mishra N, Singh AS, Tiwari VK. Ind. J. Heterocycl. Chem. 2018; 28: 125
• 22 Duangkamol C, Wangngae S, Pattarawarapan M, Phakhodee W. Eur. J. Org. Chem. 2014; 7109
• 23 Kanışkan N, Kökten S, Celik I. ARKIVOC 2012; (viii): 198
• 24 Wet-osot S, Duangkamol C, Pattarawarapan M, Phakhodee W. Monatsh. Chem. 2015; 146: 959
• 25a Katritzky AR, Shobana N, Pernak J, Afridi AS, Fan WQ. Tetrahedron 1992; 48: 7817
• 25b Katritzky AR, Zhang Y, Singh SK. Synthesis 2003; 2795
• 26 Singh AS, Agrahari AK, Mishra N, Singh M, Tiwari VK. Synthesis 2019; 51: 470
• 27 Singh M, Singh AS, Mishra N, Agrahari AK, Tiwari VK. Synthesis 2019; 51: 2183
• 28 Jang DO, Park DJ, Kim J. Tetrahedron Lett. 1999; 5323
• 29 Prusinowski AF, Twumasi RK, Wappes EA, Nagib DA. J. Am. Chem. Soc. 2020; 142: 5429
• 30 Tanaka R, Tanimoto I, Kojima M, Yoshino T, Matsunaga S. J. Org. Chem. 2019; 84: 13203
• 31 Mezailles N, Ricard L, Gagosz F. Org. Lett. 2005; 7: 4133
• 32 Gayakhe V, Ardhapure AK, Kapdi AR, Sanghvi YS, Serrano JL, García L, Pérez J, García J, Sánchez G, Fischer C, Schulzke C. J. Org. Chem. 2016; 81: 2713
• 33 Agrahari AK, Bose P, Jaiswal MK, Rajkhowa S, Singh AS, Hotha S, Mishra N, Tiwari VK. Chem. Rev. 2021; 12: 7638
• 34 Tiwari VK, Mishra BB, Mishra KB, Mishra N, Singh AS, Chen X. Chem. Rev. 2016; 116: 3086
• 35 Agrahari AK, Jaiswal MK, Yadav MS, Tiwari VK. Carbohydr. Res. 2021; 508: 108403
• 36 Agrahari AK, Singh AS, Mukharjee RK, Tiwari VK. RSC Adv. 2020; 43: 31553
• 37 Schmidt RR, Michel J. Angew. Chem., Int. Ed. Engl. 1980; 19: 731
• 38a Schmidt RR, Michel J. J. Carbohydr. Chem. 1985; 4: 141
• 38b Schmidt RR, Kinzy W. Adv. Carbohydr. Chem. Biochem. 1994; 50: 21
• 39 Maharani NS, Meador RI. L, Smith TJ, Canarelli SE, Adhikari AA, Shah JP, Russo CM, Wallach DR, Howard KT, Millimaci AM, Chisholm JD. J. Org. Chem. 2019; 84: 7871
• 40 Betori RC, Miller ER, Scheidt KA. Adv. Synth. Catal. 2017; 359: 1131
• 41 Katritzky AR, Cai C, Singh SK. J. Org. Chem. 2006; 71: 3375
• 42 Wet-osot S, Phakhodee W, Pattarawarapan M. Tetrahedron Lett. 2015; 56: 6998
• 43 Matilde CV, Nagel Heinze T. Polym. Bull. 2010; 65: 873
• 44 Pocquet L, Vologdin N, Mangiatordi GF, Ciofini I, Nicolotti O, Thorimbert S, Salmain M. Eur. J. Inorg. Chem. 2017; 3622

Publikationsverlauf

Eingereicht: 12. September 2021

Angenommen nach Revision: 27. September 2021

Accepted Manuscript online:
28. September 2021

Artikel online veröffentlicht:
13. Oktober 2021