Silicon Industry Waste Polymethylhydrosiloxane-Mediated Benzotriazole Ring Cleavage: A Practical and Green Synthesis of Diverse Benzothiazoles.

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.

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 Bu3SnH along with 5 mol % azobisisobutyronitrile (AIBN), which was further improved by our group in another report using 0.6 equiv of Bu3SnH along with excess of NaBH4 and 5 mol % AIBN (Scheme ).

Scheme 1

Previous and Present Work from Our Lab on BtRC

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 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 ).[7] PMHS is inexpensive (cost is almost ∼1.0 dollar per kilogram), stable to air, moisture, and in 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 compounds[8] 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, chemoselective[16] and enantioselective conjugate reduction[17] 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 anti-Markovnikov 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]

Figure 1

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

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.

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,2b] 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 ). 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

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,N-dimethylformamide (DMF), tetrahydrofuran (THF), and benzene was considered independently, which revealed that anhydrous THF is the best suited solvent for the BtRC reaction (Table , 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 , 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 , entry 6), whereas average yields were obtained when the reaction was carried out in the absence of AIBN (Table , 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 .

Table 1

Optimization of BtRC Reaction

entrya	PMHS (equiv by weight)	AIBN (mol %)	solventb	temp (h)	time	yield (%)c
1	1.1	5	toluene	110	5	69
2	1.1	5	benzene	110	5	60
3	1.1	5	DMF	110	5	34
4	1.1	5	DMSO	110	5	21
5	1.1	5	THF	110	5	87
6	2.0	5	solvent-free	110	5	95
7	2.0	10	solvent-free	110	5	91
8	2.0	0	solvent-free	110	5	27
9	2.0	0	solvent-free	110	10	26
10	2.0	5	solvent-free	25	5	00
11	2.0	5	solvent-free	50	5	trace
12	2.0	5	solvent-free	70	5	trace
13	2.0	5	solvent-free	130	5	81
14	2.0	5	solvent-free	160	5	74
15	2.0	5	solvent-free	110	1	37
16	2.0	5	solvent-free	110	2	49
17	2.0	5	solvent-free	110	10	94

Molar ratio: 4-chlorophenyl-1H-benzo[d][1,2,3]triazole-1-carbodithioate 1a (1.0 mmol).

Anhydrous solvents.

Yields reported after purification by column chromatography (SiO2).

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 (1b-t) following the procedures given in literature.[2a,2b] When we carried out BtRC of aryl-thio-thioacyl benzotriazole derivatives 1b & 1c with PMHS under the optimized reaction conditions (i.e., Table , 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 .

Table 2

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

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).

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 ).

Scheme 3

PMHS-Mediated BtRC Executed in the Gram Scale

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-H[2b] 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 ). 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, AIBN commences the BtRC route by generating the 2-cyanoprop-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 N-thioacyl benzotriazole 1 leading to the respective benzothiazole 2 is depicted in Scheme .

Scheme 4

Plausible Mechanism for PMHS-Mediated BtRC Leading to Benzothiazole 2

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.

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 13C 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 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/n-hexane); 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); 1H 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, 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/n-hexane); 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.

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); 1H 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/n-hexane); 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); 13C 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/n-hexane), 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-2-amine (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-2-amine (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-d-galactopyranose (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-d-glucopyranoside (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 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.