Silicon Industry Waste Polymethylhydrosiloxane-Mediated

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Article Cite This: ACS Omega 2019, 4, 6681−6689

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Silicon Industry Waste Polymethylhydrosiloxane-Mediated Benzotriazole Ring Cleavage: A Practical and Green Synthesis of Diverse Benzothiazoles Mangal S. Yadav, Anoop S. Singh, Anand K. Agrahari, Nidhi Mishra, and Vinod K. Tiwari* Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India

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S Supporting Information *

ABSTRACT: A green modification has been introduced to the synthesis of benzothiazoles by using polymethylhydrosiloxane (PMHS) for successive steps of benzotriazole ring cleavage and cyclization, an approach which was previously developed in our lab by the use of n-Bu3SnH. The use of the silicone industry byproduct PMHS makes this protocol a cost-effective and nontoxic one and thus may be considered for the industrial importance.

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INTRODUCTION The benzotriazole ring cleavage (BtRC) methodology has emerged as an interesting approach for facile synthesis of a variety of compounds including heterocycles.1,2 Reaction conditions, such as thermolysis, photolysis, organometallic reagent oxidants, and free radical reagents, cause the cleavage of the relatively stable benzotriazole ring, exhibiting fascinating chemistry.3,4 The low cost, stability, and nontoxic nature of benzotriazole moiety makes this approach an easy and economical method for organic synthesis of a large number of valuable compounds.5 Our group has been involved in the exploration of interesting features of the benzotriazole methodology for the last 10 years. We have successfully employed the BtRC approach for the synthesis of benzoxazoles, benzothiazoles, and amide derivatives mainly using free radical pathway.2 We also presented an improved approach for the synthesis of benzothiazoles via intramolecular cyclative cleavage of the benzotriazole ring of N-thioacylbenzotriazoles by using 2.2 equiv of nBu3SnH along with 5 mol % azobisisobutyronitrile (AIBN), which was further improved by our group in another report using 0.6 equiv of nBu3SnH along with excess of NaBH4 and 5 mol % AIBN (Scheme 1). Nowadays, one of the crucial challenges in front of organic synthetic chemists is to innovate and modify the established processes by removal of hazardous substances, reducing the waste product, re-use of industrial waste, and conservation of energy in the reaction in such a way that it benefits the human being, environment, and economy.6 Thus, for the past 2 decades research on green chemistry, especially green organic © 2019 American Chemical Society

Scheme 1. Previous and Present Work from Our Lab on BtRC

synthesis, is considered as one of the most promising areas, where further utilization of industrial waste materials is the main goal. Polymethylhydrosiloxane (PMHS), a polymer with the general structure −(CH3(H)Si−O)− is a silicon industry byproduct (Figure 1).7 PMHS is inexpensive (cost is almost ∼1.0 dollar per kilogram), stable to air, moisture, and in Received: February 6, 2019 Accepted: March 29, 2019 Published: April 11, 2019 6681

DOI: 10.1021/acsomega.9b00343 ACS Omega 2019, 4, 6681−6689

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After establishment of PMHS as a suitable reagent for BtRC, we tried to find out the optimum reaction conditions for the high product yields with minimum use of a reagent. In this respect, solvent, reaction time, and reaction temperature were optimized to get the best reaction yield with great ease. First of all, optimization of the solvent including toluene, N,Ndimethylformamide (DMF), tetrahydrofuran (THF), and benzene was considered independently, which revealed that anhydrous THF is the best suited solvent for the BtRC reaction (Table 1, entry 5). To our pleasant surprise, the cleavage reaction also went smoothly and satisfactorily in neat condition, that is the solvent-free condition producing respective benzothiazole 2a in excellent yield (Table 1, entry 6). After optimization of the reaction medium, we investigated the loading of AIBN and found that reaction produces a maximum yield with 5 mol % loading of AIBN (Table 1, entry 6), whereas average yields were obtained when the reaction was carried out in the absence of AIBN (Table 1, entries 8 and 9). We also optimized the reaction temperature and found that lowering of the temperature reduced the product yields drastically and at room temperature the reaction did not move at all. At a temperature above 120 °C, the reaction goes around 80% with a number of side products. The most favorable condition for the reaction was found to be entry no. 6 of Table 1. After optimization of the reaction conditions with reactant 1a, we further tried to generalize the use of PMHS in BtRC of a variety of thioacyl benzotriazoles (1b-t). We successfully developed various types of arylthio-thioacyl benzotriazoles including N-(ferrocenylmethyl)-N′-dialkylthiocarbamoyl benzotriazole, N,N′-dialkylthiocarbamoyl benzotriazole, and carbohydrate-based benzotriazole methanethione derivatives (1bt) following the procedures given in literature.2a,b When we carried out BtRC of aryl-thio-thioacyl benzotriazole derivatives 1b & 1c with PMHS under the optimized reaction conditions (i.e., Table 1, entry no. 6), it was found that 1b & 1c undergo complete conversion on thin layer chromatography (TLC) and give up to 98% yield after purification by column chromatography, but N,N′-dialkylthiocarbamoyl benzotriazole (1d-m), N-(ferrocenylmethyl)-N′-dialkylthiocarbamoyl benzotriazole (1n-q), and carbohydrate-based benzotriazole methanethione derivatives (1r-t) give moderate to good yields of respective benzothiazole (2b-t) in pure form after purification by column chromatography (SiO2). A result of BtRC chemistry using PMHS is depicted in Table 2. For the quantitative generalization of the above-established BtRC reaction with PMHS, we applied the optimized reaction in gram scales and found that PMHS works equally well as a solvent and a reagent in the grams scale synthesis of benzothiazole 2a via the BtRC route (Scheme 3). Mechanism of the PMHS-mediated BtRC is envisaged to follow the similar cleavage chemistry reported earlier by utilizing tributyl tin hydride (Bu3SnH)2a or TMS-H2b under free radical condition, where the ring opening of thioacyl benzotriazole 1 occurs via β-scission of N−N bond followed by ring closure through the elimination of molecular nitrogen (N2), thus resulting in the respective benzothiazole heterocyclic skeleton 2 (Scheme 4). Our previous investigation based on Density Functional Theory (DFT) calculation using Pople basis sets 6-31G (d,p) is further supported to predict Si−S bonding strength (in TMS-H) and it also supports the existence of intermediate radical I (in PMHS) that we have postulated in our present mechanistic pathway.2b Likewise,

Figure 1. Structure of poly(methylhydrosiloxane) (PMHS), a cheap, stable, nontoxic, and biodegradable industrial waste.

organic solvents, having low viscosity, and moreover it is a biodegradable and nontoxic reagent.7a Therefore, this reagent may be considered as a green alternative reagent for wide applications in organic synthesis.7−22 For example, PMHS has been successfully used for the chemoselective reductive amination of a variety of carbonyl compounds8 and also asymmetric hydrosilylation of heteroaromatic ketones.9 In addition, PMHS has also been utilized for the reduction of other systems including ketone to alkane,10 tert amide to amine,11 alkyne to alkene,12 aromatic/aliphatic nitro groups to respective amines,13 aromatic acid chlorides to respective aldehydes,14 and indole to indoline.15 Interestingly, chemoselective16 and enantioselective conjugate reduction17 has also been achieved successfully using this silicon industry waste reagent. Furthermore, hydrocarbonylative C−C coupling of terminal alkynes with alkyl iodide (RI), 18 and antiMarkovnikov hydroallylation with functionalized alkynes were well investigated using PMHS.19 Although, PMHS was well utilized for the synthesis of benzothiazole and the related heterocycle,20 and also for the selective cleavage of allyl ethers, amines, and esters.21 However, this reagent is little explored for the purpose of ring opening reaction in order to afford biologically relevant molecules.2f,22 In the present work, we wish to report a modified BtRC protocol for the synthesis of diverse benzothiazoles comprising an improved green approach under the free radical condition by the use of a silicon industry waste product PMHS in place of n-Bu3SnH.

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RESULTS AND DISCUSSION Our synthetic strategy begins with the preparation of benzotriazole methanethione derivatives, which were obtained from corresponding thiols or secondary amines or alcohols by treating them with bis-benzotriazole methanethione under the standard reaction condition (see the Supporting Information, Scheme S1).2a,b For establishment of PMHS as a competent alternative of n-Bu3SnH for BtRC, we set up a prototype reaction with 1.0 equiv of 4-chlorophenyl-1H-benzo[d][1,2,3]triazole-1-carbodithioate 1a and 1.1 equiv of PMHS by weight in the presence of 5 mol % of AIBN in anhydrous toluene at 90 °C for 5 h (Scheme 2). The reaction mass was concentrated under reduced pressure and the reaction product 2a was purified through column chromatography (SiO2). A 69% yield of the desired product 2a was obtained, which suggested that PMHS can efficiently cleave the benzotriazole ring. Scheme 2. Prototype BtRC Reaction for the Synthesis of Benzothiazole 2a

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Table 1. Optimization of BtRC Reaction

entrya

PMHS (equiv by weight)

AIBN (mol %)

solventb

temp (h)

time

yield (%)c

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

1.1 1.1 1.1 1.1 1.1 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0

5 5 5 5 5 5 10 0 0 5 5 5 5 5 5 5 5

toluene benzene DMF DMSO THF solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free solvent-free

110 110 110 110 110 110 110 110 110 25 50 70 130 160 110 110 110

5 5 5 5 5 5 5 5 10 5 5 5 5 5 1 2 10

69 60 34 21 87 95 91 27 26 00 trace trace 81 74 37 49 94

a Molar ratio: 4-chlorophenyl-1H-benzo[d][1,2,3]triazole-1-carbodithioate 1a (1.0 mmol). bAnhydrous solvents. cYields reported after purification by column chromatography (SiO2).

of the reaction on TLC, which was visualized by observing it in a UV chamber (λmax = 254 nm), organic scaffolds were purified by flash column chromatography (SiO2). General Experimental Procedure for the Synthesis of Benzothiazole Scaffolds 2a−2t. Benzotriazole methanethione derivative 1 (1.0 mmol) was taken with AIBN (5−10 mol %) and the PMHS reagent as well as a solvent, and the resulting reaction mixture was stirred at 110 °C for about 5−6 h. After the completion of the reaction (the progress of the reaction was monitored by TLC), the crude solution was subjected to reduced pressure using a rotary evaporator to obtain the crude mass. Furthermore, the crude residues were purified by flash column chromatography (SiO2) using the gradient of ethyl acetate/n-hexane (2−30%) to obtain the corresponding benzothiazole moieties (2a−2t). Physical Data of the Synthesized Compounds (2a−t). 2-(4-Chlorophenylthio)benzo[d]thiazole (2a).2b,25 Yellow solid, yield: 0.266 g (95%); Rf = 0.8 (5% ethyl acetate/nhexane); mp 51−52 °C; 1H NMR (500 MHz, CDCl3): δ 7.88 (d, J = 7.5 Hz, 1H), 7.69−7.65 (m, 3H), 7.46−7.40 (m, 3H), 7.30−7.27 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 168.2, 153.8, 136.9, 136.4, 135.5, 130.1, 128.4, 126.2, 124.5, 122.1, and 120.8 ppm. 2-(Benzylthio)benzo[d]thiazole (2b).2b,26 Yellow solid, yield: 0.246 g (98%); Rf = 0.8 (5% ethyl acetate/n-hexane); mp 38−39 °C; 1H NMR (500 MHz, CDCl3): δ 7.90 (d, J = 8.5 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.46−7.41 (m, 3H), 7.35−7.28 (m, 4H), 4.61 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 166.3, 153.1, 136.1, 135.3, 129.1, 128.6, 127.7, 126.0, 124.2, 121.5, 120.9, and 37.7 ppm. 2-(2-Chlorobenzylthio)benzo[d]thiazole (2c).2b,27 Yellow oil, yield: 0.262 g (90%); Rf = 0.8 (5% ethyl acetate/n-hexane); 1 H NMR (500 MHz, CDCl3): δ 7.92 (d, J = 8.5 Hz, 1H), 7.74 (d, J = 7.5 Hz, 1H), 7.60 (dd, J = 6.5 Hz, 4.5 Hz, 1H), 7.44− 7.39 (m, 2H), 7.31−7.28 (m, 1H), 7.23−7.19 (m, 2H), 4.74 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 166.0, 153.0, 135.4,

AIBN commences the BtRC route by generating the 2cyanoprop-2-yl radical, which quickly reacts with PMHS and results in a PMS radical (PMS•).23 This radical first attacks the thione group of RCSBt 1 and generates similar type of radical intermediates I and II, which, on benzotriazole ring opening, gives biradical intermediate III followed by elimination of molecular nitrogen and consequent attack of sulphur (resulted in the respective intermediates IV and V) followed by oxidative aromatization at the cost of the 2σ-bond, resulting in a π-bond in the respective benzothiazole 2. In the support of the free radical mechanism, we also added TEMPO (a well-known free radical inhibitor) in the optimized reaction, which resulted in only 14% product yield, which clearly suggests that free radical formation has taken place during the course of reaction.24 The plausible mechanism for the PMHS-mediated BtRC of Nthioacyl benzotriazole 1 leading to the respective benzothiazole 2 is depicted in Scheme 4.

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CONCLUSIONS In brief, we have established industrial waste PMHS (PMHS) as an efficient reagent for the BtRC of N-thioacyl benzotriazoles for easy access of benzothiazole derivatives. Furthermore, this reagent is a cheap and waste product of the silicone industry, which works equally well even in neat conditions, making this BtRC protocol a cost-effective, nontoxic, and more applicable and greener than previous investigated methods.

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EXPERIMENTAL SECTION General Remarks. The starting materials were synthesized by using standard known procedures. The commercially available Merck and Sigma-Aldrich solvents and reagents were used as such without further purification. 1H NMR and 13 C NMR spectra were recorded at 500 and 125 MHz in a spectrometer, respectively. The reactions were performed in sealed tubes under optimized conditions. After the completion 6683

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Table 2. PMHS-Mediated BtRC towards a Green Aspect Synthesis of Respective Benzothiazoles (2a−t) from the Corresponding Thioacylbenzotriazoles (1a−t)a

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Table 2. continued

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Table 2. continued

Molar ratios: 1a−t (1.0 equiv), PMHS (equiv by weight), AIBN (5 mol %), 110 °C, 2−5 h. Yields are after flash column chromatography (SiO2).

a

Scheme 3. PMHS-Mediated BtRC Executed in the Gram Scale

Scheme 4. Plausible Mechanism for PMHS-Mediated BtRC Leading to Benzothiazole 2

134.4, 134.3, 131.2, 129.7, 129.1, 126.9, 126.0, 124.2, 121.5, 121.0, and 35.2 ppm. 2-(Piperidin-1-yl)benzo[d]thiazole (2d).2b White crystal, yield: 0.202 g (91%); Rf = 0.7 (20% ethyl acetate/n-hexane); mp 82−83 °C; 1H NMR (500 MHz, CDCl3): δ 7.58−7.52 (m, 2H), 7.29−7.25 (m, 1H), 7.06−7.03 (m, 1H), 3.60 (s, 4H), 1.69 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 168.8, 152.9, 130.6, 125.8, 121.0, 120.5, 118.7, 49.6, 25.2, and 24.2 ppm. 2-(4-Phenylpiperazin-1-yl)benzo[d]thiazole (2e).2b White crystal, yield: 0.178 g (61%); Rf = 0.6 (20% ethyl acetate/nhexane); mp 181−182 °C; 1H NMR (500 MHz, CDCl3): δ 7.52−7.49 (m, 2H), 7.20 (q, J = 7.5 Hz, 3H), 6.99 (t, J = 7.5 Hz, 1H), 6.86−6.80 (m, 3H), 3.68 (t, J = 5.0 Hz, 4H)), 3.20− 3.18 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 168.8, 152.8,

151.1, 130.9, 129.4, 126.2, 121.7, 120.9, 120.8, 119.4, 117.0, 49.2, and 48.5 ppm. 6686

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2-(4-Pyridin-2-yl)benzo[d]thiazole (2f).2b White crystal, yield: 0.234 g (80%); Rf = 0.5 (20% ethyl acetate/n-hexane); mp 192−193 °C; 1H NMR (500 MHz, CDCl3): δ 8.22 (d, J = 4.5 Hz, 1H), 7.63−7.51 (m, 3H), 7.53−7.50 (m, 1H), 7.33− 7.29 (m, 1H), 7.09 (t, J = 7.5 Hz, 1H), 6.71−6.67 (m, 2H), 3.78−3.76 (m, 4H), 3.73−3.71 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 168.8, 159.1, 152.6, 148.1, 137.8, 130.7, 126.1, 121.6, 120.8, 119.2, 114.1, 107.4, 48.1, and 44.8 ppm. N,N-Dibutylbenzo[d]thiazol-2-amine (2g).2b Yellow oil, yield: 0.236 g (90%); Rf = 0.8 (20% ethyl acetate/n-hexane); 1 H NMR (500 MHz, CDCl3): δ 7.55−7.49 (m, 2H), 7.26− 7.22 (m, 1H), 7.01−6.98 (m, 1H), 3.50−3.47 (m, 4H), 1.70− 1.64 (m, 4H), 1.41−1.34 (m, 4H), 0.97−0.94 (m, 6H); 13C NMR (125 MHz, CDCl3): δ 167.9, 153.2, 130.6, 125.7, 120.5, 120.3, 118.5, 50.9, 29.6, 20.1, and 13.8 ppm. N,N-Dibenzylbenzo[d]thiazole-2-amine (2h).28 Yellow solid, yield: 0.205 g (62%); Rf = 0.6 (20% ethyl acetate/nhexane); mp 119−120 °C; 1H NMR (500 MHz, CDCl3): δ 7.59 (d, J = 8.5 Hz, 2H), 7.34−7.27 (m, 11H), 7.10−7.06 (m, 1H), 4.73 (s, 4H); 13C NMR (125 MHz, CDCl3): δ 169.1, 152.9, 136.2, 128.7, 127.79, 127.71, 126.0, 121.2, 120.6, 119.0, 113.9, and 53.2 ppm. 4-(Benzo[d]thiazol-2-yl)morpholine (2i).2b White crystal, yield: 0.161 g (73%); Rf = 0.5 (20% ethyl acetate/n-hexane); mp 123−124 °C; 1H NMR (500 MHz, CDCl3): δ 7.62−7.56 (m, 2H), 7.32−7.29 (m, 1H), 7.09 (t, J = 7.5 Hz, 1H), 3.84− 3.82 (m, 4H), 3.63−3.61 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 168.7, 152.2, 130.3, 125.8, 121.4, 120.5, 119.0, 65.9, and 48.2 ppm. 2-(1H-Benzo[d][1,2,3]triazol-1-yl)benzo[d]thiazole (2j).2b White crystal, yield: 0.214 g (85%); Rf = 0.6 (20% ethyl acetate/n-hexane); mp 175−176 °C; 1H NMR (500 MHz, CDCl3): δ 8.68 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 7.5 Hz, 1H) , 8.06 (d, J = 8.5 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.75−7.72 (m, 1H), 7.55 (t, J = 7.0 Hz, 2H), 7.47−7.43 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 157.3, 150.8, 146.8, 132.4, 131.2, 130.0, 126.8, 125.9, 125.6, 123.0, 121.6, 120.2, and 113.9 ppm. (E)-2-(4-Cinnamylpiperazin-1-yl)benzo[d]thiazole (2k).2b White crystal, yield: 0.252 g (76%); Rf = 0.7 (50% ethyl acetate/n-hexane), mp 122−123 °C; 1H NMR (500 MHz, CDCl3): δ 7.52−7.47 (m, 2H), 7.35−7.15 (m, 6H), 7.01−6.98 (m, 1H), 6.47 (d, J = 15 Hz, 1H), 6.23−6.17 (m, 1H), 3.61− 3.59 (m, 4H), 3.15 (d, J = 7.0 Hz, 2H), 2.58−2.56 (m, 4H); 13 C NMR (125 MHz, CDCl3): δ 168.7, 152.6, 136.6, 133.6, 130.6, 128.5, 127.6, 126.3, 126.0, 125.7, 121.4, 120.6, 119.0, 60.9, 52.3, and 48.3 ppm. 2-(4-Methylpiperazin-1-yl)benzo[d]thiazole (2l).2b White crystal, yield: 0.202 g (87%); Rf = 0.7 (80% ethyl acetate/nhexane), mp 94−95 °C; 1H NMR (500 MHz, CDCl3): δ 7.55−7.51 (m, 2H), 7.24 (t, J = 7.5 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 3.60−3.58 (m, 4H), 2.47−2.45 (m, 4H), 2.28 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 168.5, 152.5, 130.5, 125.8, 121.2, 120.5, 118.9, 54.0, 48.0, and 45.9 ppm. 2-(4-Chlorophenyl)piperazin-1-yl)benzo[d]thiazole (2m).2b White crystal, yield: 0.220 g (67%); Rf = 0.7 (20% ethyl acetate/n-hexane), mp 122−124 °C; 1H NMR (500 MHz, CDCl3): δ 7.62 (d, J = 8.5 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.40−7.38 (m, 1H), 7.32−7.29 (m, 1H), 7.25−7.22 (m, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.05−7.00 (m, 2H), 3.83−3.81 (m, 4H), 3.19−3.17 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 168.8, 152.6, 148.6, 130.7, 128.9, 127.6, 126.0, 124.3, 121.5, 120.7, 120.5, 119.1, 50.7, and 48.6 ppm.

N-(Furan-2-yl-methyl)-N-(ferrocenylmethyl)benzo[d]thiazol-2-amine (2n).2b Red crystal, yield: 0.342 g (74%); Rf = 0.7 (20% ethyl acetate/n-hexane), mp 99−100 °C; 1H NMR (500 MHz, CDCl3): δ 7.59 (d, J = 8.5 Hz, 2H), 7.39 (s, 1H), 7.31−7.28 (m, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.34 (d, J = 2.0 Hz, 1H), 6.29 (d, J = 4.0 Hz, 1H), 4.63 (s, 2H), 4.52 (s, 2H), 4.31 (s, 2H), 4.19 (s, 5H), 4.14 (t, J = 2.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 167.7, 152.8, 150.2, 142.3, 130.8, 125.8, 121.1, 120.5, 118.9, 110.3, 108.7, 82.0, 69.6, 68.6, 68.3, 49.5, and 45.6 ppm. N-Benzyl-N-(ferrocenylmethyl)benzo[d]thiazol-2-Amine (2o).2b Red crystal, yield: 0.395 g (84%); Rf = 0.7 (20% ethyl acetate/n-hexane), mp 151−152 °C; 1H NMR (500 MHz, CDCl3): δ 7.50 (t, J = 7.5 Hz, 2H), 7.24−7.19 (m, 6H), 6.99 (d, J = 7.0 Hz, 1H), 4.59 (s, 2H), 4.42 (s, 2H), 4.17 (s, 2H), 4.08 (s, 5H), 4.04 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 168.4, 152.9, 136.4, 130.7, 128.6, 127.7, 127.4, 125.8, 121.0, 120.5, 118.8, 82.0, 69.6, 68.6, 68.3, 52.8, and 49.3 ppm. N-Cyclohexyl-N-(ferrocenylmethyl)benzo[d]thiazol-2amine (2p).2b Red crystal, yield: 0.309 g (67%); Rf = 0.7 (20% ethyl acetate/n-hexane), mp 134−135 °C; 1H NMR (500 MHz, CDCl3): δ 7.55−7.52 (m, 2H), 7.24−7.22 (m, 1H), 6.99 (t, J = 7.5 Hz, 1H), 4.49 (s, 2H), 4.38 (s, 2H), 4.17 (s, 5H), 4.05 (s, 2H), 3.77−3.73 (m, 1H), 1.84−1.79 (m, 4H), 1.53− 1.46 (m, 2H), 1.37−1.30 (m, 2H), 1.15−1.09 (m, 1H), 0.90− 0.87 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 168.0, 153.2, 130.6, 125.7, 120.7, 120.4, 118.7, 85.1, 70.0, 68.8, 67.8, 61.2, 46.0, 31.1, 26.1, and 25.6 ppm. N-(Ferrocenylmethyl)-N-phenethylbenzo[d]thiazol-2amine (2q).2b Red crystal, yield: 0.352 g (73%); Rf = 0.7 (20% ethyl acetate/n-hexane), mp 158−159 °C; 1H NMR (500 MHz, CDCl3): δ 7.62−7.59 (m, 2H), 7.33−7.30 (m, 3H), 7.25−7.20 (m, 3H), 6.07 (t, J = 7.5 Hz, 1H), 4.47 (s, 2H), 4.29 (s, 2H), 4.19 (s, 5H), 4.15 (s, 2H), 3.62−3.59 (m, 2H), 2.92− 2.89 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 167.3, 153.2, 138.8, 130.7, 128.8, 128.5, 126.4, 125.8, 120.9, 120.5, 118.7, 182.5, 69.5, 68.7, 68.4, 52.0, 50.4, and 33.5 ppm. 6-O-(Benzothiazol-2′-yl)-1,2;3,4-di-O-isopropylidene-α-Dgalactopyranose (2r).2a White crystal, yield: 0.305 g (78%); Rf = 0.8 (20% ethyl acetate/n-hexane), mp 100−102 °C; 1H NMR (500 MHz, CDCl3): δ 7.66−7.62 (m, 2H), 7.36−7.33 (m, 1H), 7.23−7.20 (m, 1H), 5.58 (d, J = 5 Hz, 1H), 4.78− 4.75 (m, 1H), 4.68−4.64 (m, 2H), 4.38−4.34 (m, 3H), 1.48 (s, 6H), 1.36 (s, 3H), 1.32 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 172.5, 149.2, 132.1, 125.8, 123.4, 121.2, 120.8, 109.7, 108.8, 96.3, 70.9, 70.7, 70.4, 70.2, 65.6, 25.97, 25.95, 24.9, and 24.4 ppm. 5-O-(Benzothiazol-2′-yl)-3-O-benzyl-1,2-O-isopropylidine-α-D-xylofuranose (2s).2a Yellow liquid, yield: 0.364 g (88%); Rf = 0.7 (20% ethyl acetate/n-hexane); 1H NMR (500 MHz, CDCl3): δ 7.69 (d, J = 8.5 Hz, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.38−7.33 (m, 3H), 7.27−7.20 (m, 4H), 5.79 (d, J = 3.5 Hz, 1H), 4.82−4.76 (m, 2H), 4.68−4.55 (m, 3H), 4.41−4.38 (m, 1H), 3.87−3.84 (m, 1H), 1.63 (s, 3H), 1.38 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 172.4, 149.0, 137.1, 132.0, 128.4, 128.0, 127.9, 125.9, 123.5, 121.2, 120.8, 113.1, 104.1, 77.08, 77.06, 76.4, 72.3, 69.4, 26.7, and 26.4 ppm. Methyl 6-O-(Benzothiazol-2′-yl)-2,3,4-tri-O-benzyl-α-Dglucopyranoside (2t).2a White solid, yield: 0.501 g (84%); Rf = 0.8 (20% ethyl acetate/n-hexane); 1H NMR (500 MHz, CDCl3): δ 7.66−7.61 (m, 2H), 7.36−7.27 (m, 10H), 7.24− 7.16 (m, 7H), 5.01 (d, J = 11.5 Hz, 1H), 4.87−4.79 (m, 4H), 4.69−4.65 (m, 2H), 4.62 (d, J = 2.5 Hz, 1H), 4.57 (d, J = 10.5 6687

DOI: 10.1021/acsomega.9b00343 ACS Omega 2019, 4, 6681−6689

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Two-step Organic Chemistry Experiment for Undergraduate and Postgraduate Students. J. Heterocycl. Chem. 2019, 56, 275−280. (3) (a) Micó, X. I.; Ziegler, T.; Subramanian, L. R. A versatile Direct Approach to ortho-Substituted Azobenzenes from Benzotriazoles. Angew. Chem. Int. Ed. 2004, 43, 1400−1403. (b) Uhde, M.; Ziegler, T. Reaction of N-Nitro-Benzotriazole with Nucleophiles. Synth. Commun. 2010, 40, 3046−3057. (c) Katritzky, A. R.; Ji, F. B.; Fan, W. Q.; Gallos, J. K.; Greenhill, J. V.; King, R. W.; Steel, P. J. Novel Dimroth Rearrangements of the Benzotriazole System: 4-Amino-l(arylsulfonyl)benzotriazoles to 4-[(Arylsulfonyl) amino]benzotriazoles. J. Org. Chem. 1992, 57, 190−195. (d) Habraken, C. L.; Erkelens, C.; Mellema, J. R.; Cohen-Fernandes, P. 1-Nitrobenzotriazole-2-(Nitroimino) diazobenzene Isomerization: Formation of Triazenes by Azo Coupling with Cyclic Amines. Structure Determination and Dynamic NMR. J. Org. Chem. 1984, 49, 2197− 2200. (e) Katritzky, A. R.; Akue-Gedu, R.; Vakulenko, A. V. CCyanation with 1-Cyanobenzotriazole. ARKIVOC 2007, 3, 5−12. (4) (a) Katritzky, A. R.; Yang, B.; Dalal, N. S. Novel HeteroatomLinked Analogues of Trityl Radicals: Diaryl(benzotriazol-1-yl)methyl Radical Dimers. J. Org. Chem. 1998, 63, 1467−1472. (b) Kim, T.; Kim, K. Practical method for synthesis of 2,3-disubstituted indole derivatives promoted by β-(benzotriazol-1-yl)allylic O-stannyl ketyl radicals. Tetrahedron Lett. 2010, 51, 868−871. (5) (a) Katritzky, A. R.; Rogovoy, B. V.; Kirichenko, N.; Vvedensky, V. Solid-Phase Preparation of Amides Using N-Acylbenzotriazoles. Bioorg. Med. Chem. Lett. 2002, 12, 1809−1811. (b) Katritzky, A. R.; Suzuki, K.; Singh, S. K.; He, H.-Y. Regiospecific C-Acylation of Pyrroles and Indoles Using N-AcylbenzotriazolesRegiospecificCAcylation of Pyrroles and Indoles UsingN-Acylbenzotriazoles. J. Org. Chem. 2003, 68, 5720−5723. (c) Wang, X.; Zhang, Y. LowValent Titanium Promoted Self-Coupling ofN-Acylbenzotriazoles and Their Cross-Coupling with Diarylketones. Synth. Commun. 2003, 33, 2627−2634. (d) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. Expedient Acylations of Primary and Secondary Alkyl Cyanides to αSubstituted β-Ketonitriles. J. Org. Chem. 2003, 68, 4932−4934. (e) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. Efficient Conversion of Sulfones intoβ-Keto Sulfones byN-Acylbenzotriazoles§. J. Org. Chem. 2003, 68, 1443−1446. (f) Katritzky, A. R.; Cai, C.; Suzuki, K.; Singh, S. K. Facile Syntheses of Oxazolines and Thiazolines withN-Acylbenzotriazoles under Microwave Irradiation. J. Org. Chem. 2004, 69, 811−814. (g) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Gromova, A. V.; Witek, R.; Steel, P. J. α-Nitro Ketone Synthesis UsingN-Acylbenzotriazoles. J. Org. Chem. 2005, 70, 9211−9214. (h) Katritzky, A. R.; Suzuki, K.; Wang, Z. Acylbenzotriazoles as Advantageous N-, C-, S-, and O-Acylating Agents. Synlett 2005, 1656−1665. (i) Lim, D.; Fang, F.; Zhou, G.; Coltart, D. M. Direct Carbon−Carbon Bond Formation via Soft Enolization: A Facile and Efficient Synthesis of 1,3-Diketones. Org. Lett. 2007, 9, 4139−4142. (j) Wang, X.; Wang, W.; Wen, Y.; He, L.; Zhu, X. Facile and Highly Regiospecific Synthesis of 2-Aryl-Substituted Pyrazolidin-3-ones from α,β-Unsaturated N-Acylbenzotriazoles and Arylhydrazines. Synthesis 2008, 2008, 3223−3228. (k) Zhou, G.; Lim, D.; Fang, F.; Coltart, D. M. A Practical Synthesis of b-Keto Thioesters by Direct CrossedClaisen Coupling of Thioesters and N-Acylbenzotriazoles. Synthesis 2009, 3350−3352. (l) Li, J.; Sun, Y.; Chen, Z.; Su, W. A Novel and Efficient Reaction of Imidazolidin-2-one andN-Acylbenzotriazoles: A Facile Synthesis of 1-Acylimidazolidin-2-one. Synth. Commun. 2010, 40, 3669−3677. (m) Xia, Z.; Lv, X.; Wang, W.; Wang, X. Regioselective addition of thiophenol to α,β-unsaturated Nacylbenzotriazoles. Tetrahedron Lett. 2011, 52, 4906−4910. (6) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University Press: New York, 1998; p. 30. (7) (a) J. M., Lavis, R. E., Maleczka, Jr. Polymethylhydrosiloxane Encyclopedia of Reagents for Organic Synthesis 2003; John Wiley & Sons, 2003. (b) Chandrasekhar, S.; Chandrashekar, G.; Nagendra Babu, B.; Vijeender, K.; Venkatram Reddy, K. Reductive etherification of carbonyl compounds with alkyl trimethylsilylethers using polymethylhydrosiloxane (PMHS) and catalytic B(C 6 F 5 ) 3. Tetrahedron Lett. 2004, 45, 5497−5499. (c) Lawrence, N. J.; Drew,

Hz, 1H), 4.03 (t, J = 9.5 Hz, 1H), 3.95−3.93 (m, 1H), 3.65− 3.56 (m, 2H), 3.38 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 172.5, 149.1, 138.6, 138.0, 137.7, 131.9, 128.49, 128.43, 128.3, 128.1, 128.0, 127.9, 127.8, 127.6, 125.9, 123.5, 121.2, 120.8, 98.2, 82.0, 79.8, 75.8, 75.1, 73.4, 70.0, 68.8, and 55.3 ppm.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b00343.

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Copies of 1H and 13C NMR of all the developed benzothiazoles (2a−t) (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected], [email protected]. Fax: (+91) 542-236817. ORCID

Vinod K. Tiwari: 0000-0001-9244-8889 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors gratefully acknowledge the Science and Engineering Research Board (SERB), New Delhi, for the funding (grant no.: EMR/2016/001123) and sincerely thank CISC-Banaras Hindu University (BHU) for providing spectroscopic studies of the developed molecules. M.S.Y. (award no: 09/013(0794)/ 2018-EMR-I) and A.K.A. (award no: 09/013(0671)/2017EMR-I) gratefully acknowledge the CSIR, New Delhi, for their JRF fellowship.

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REFERENCES

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DOI: 10.1021/acsomega.9b00343 ACS Omega 2019, 4, 6681−6689

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DOI: 10.1021/acsomega.9b00343 ACS Omega 2019, 4, 6681−6689