A method for synthesizing benzothiazoline

Abstract

The present invention discloses a method for synthesizing benzothiazoline. Under the co-catalysis of yttrium bis(trimethylsilylamide) and tris(pentafluorophenyl)borane, an additive, a hydrogen source, and a benzothiazole compound react in a solvent to obtain a benzothiazoline compound; the structural formula of the benzothiazole compound is as follows. The structural formula of the benzothiazoline compound is as follows. The present invention provides the following technical solution: a method that can synthesize benzothiazoline compounds from various substituted benzothiazoles with high selectivity and high yield, has a wide range of raw material sources, simple and easily prepared catalysts, is easy to operate, and has mild reaction conditions.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing structurally diverse benzothiazolines by co-catalyzing the hydrogen transfer reduction reaction of benzothiazole compounds with yttrium bis(trimethylsilylamide) and tris(pentafluorophenyl)borane. Background Art

[0002] Benzothiazoline compounds are structural motifs commonly found in naturally occurring alkaloids and many bioactive compounds, and are also important components in pharmaceutical synthesis, agrochemical synthesis, and materials science. The catalytic hydrogenation reaction of benzothiazole with hydrogen molecules catalyzed by metals is a common method for preparing benzothiazolines. Benzothiazolines can also be prepared by catalytic hydrogen transfer reduction (Chem. Commun. 2017, 53, 9269). However, these reactions have certain limitations, such as the cumbersome preparation of catalysts, harsh reaction conditions, narrow substrate scope, low functional compatibility, poor chemoselectivity, and the generation of a large amount of toxic waste. Summary of the Invention

[0003] To achieve the above object, the present invention provides the following technical solution: A method for synthesizing benzothiazoline compounds with a wide range of raw material sources, simple and easy-to-prepare catalysts, and simple operation, which can highly selectively and highly yield benzothiazoline compounds from various substituted benzothiazoles as raw materials under mild reaction conditions.

[0004] A method for synthesizing benzothiazoline,

[0005] Reacting an additive, a hydrogen source, and a benzothiazole compound in a solvent under the co-catalysis of yttrium bis(trimethylsilylamide) and tris(pentafluorophenyl)borane to obtain a benzothiazoline compound;

[0006] The structural formula of the benzothiazole compound is The structural formula of the benzothiazoline compound is

[0007] As a further improvement of the present invention,

[0008] In the structural formula of the benzothiazole compound and the structural formula of the benzothiazoline compound, R is hydrogen or 2-methyl or 5-bromo or 2-p-methoxyphenyl or 2-propyl or 2-phenyl or 2-β-naphthyl.

[0009] As a further improvement of the present invention,

[0010] The additive is p-trifluoromethylaniline.

[0011] As a further improvement of the present invention,

[0012] The hydrogen source is pinacolborane.

[0013] As a further improvement of the present invention,

[0014] the solvent is toluene.

[0015] As a further improvement of the present invention,

[0016] The reaction temperature is 50 °C and the reaction time is 12 h.

[0017] As a further improvement of the present invention,

[0018] The molar ratio of the benzothiazole compound, yttrium bis(trimethylsilylamide), tris(pentafluorophenyl)borane, additive, and hydrogen source is 1.0∶0.1∶0.1∶0.1∶5.0.

[0019] The reaction equation of the present invention is:

[0020]

[0021] Through in-depth and meticulous research, the inventor of the present invention has discovered an efficient synthesis method for benzothiazoline compounds. Under the yttrium bis(trimethylsilylamide) / tris(pentafluorophenyl)borane catalytic system, the benzothiazole compound undergoes a hydrogen transfer reduction reaction, thereby realizing the synthesis of benzothiazoline with diverse structures. This method has wide sources of raw materials, is easy to operate, has broad universality, and high selectivity. Compared with previous methods, its environmental friendliness and substrate universality have been significantly improved, which is difficult to achieve by other methods. The present invention has the following advantages and innovations:

[0022] (1) The reaction has good universality and high yield, and the yield of most reactions is above 80%;

[0023] (2) This is an important supplement to the preparation of benzothiazoline compounds and provides an important idea for the synthesis of bioactive compounds.

[0024] The beneficial effects of the present invention compared with the prior art:

[0025] The benzothiazoline prepared by the method of the present invention has high quality, high yield, good reaction universality, and convenient post-treatment, providing an important reference for constructing benzothiazoline compounds. Detailed implementation manners

[0026] The present invention will be further described below by way of examples, but the examples do not limit the protection scope of the present invention.

[0027] Example 1

[0028] The preparation of benzothiazoline, the structural formula is as follows:

[0029]

[0030] Add 0.5 mmol of the starting material benzothiazole and the catalyst yttrium bis(trimethylsilylamide) (0.1 equiv) / tris(pentafluorophenyl)borane (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacolborane (2.5 mmol), toluene (1.5 mL), and react at 50 °C for 12 hours. The isolated yield of the product is 85%.

[0031] 1 H NMR (400 MHz, CDCl3) δ 7.13 (d, J = 7.5 Hz, 1H), 6.93 (t, J = 7.6 Hz, 1H), 6.78 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 7.7 Hz, 1H), 4.83 (d, J = 2.2 Hz, 2H), 4.00 (brs, 1H); 13 C NMR (101 MHz, CDCl3) δ 147.3, 128.9, 125.3, 122.2, 121.5, 111.8, 53.2.

[0032] Example 2

[0033] Preparation of 2-methylbenzothiazoline, the structural formula is as follows:

[0034]

[0035] Add 0.5 mmol of the starting material 2-methylbenzothiazole and the catalyst yttrium bis(trimethylsilylamide) (0.1 equiv) / tris(pentafluorophenyl)borane (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacolborane (2.5 mmol), toluene (1.5 mL), and react at 50 °C for 12 hours. The isolated yield of the product is 81%.

[0036] 1 H NMR (400 MHz, CDCl3) δ 7.08 (dd, J = 7.6, 0.9 Hz, 1H), 6.92 (td, J = 7.6, 1.2 Hz, 1H), 6.76 (td, J = 7.5, 1.1 Hz, 1H), 6.67 (dd, J = 7.8, 0.7 Hz, 1H), 5.40 (q, J = 6.0 Hz, 1H), 4.03 (brs, 1H), 1.62 (d, J = 6.1 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 146.5, 128.3, 125.3, 122.2, 121.2, 111.3, 64.0, 24.5.

[0037] Example 3

[0038] Preparation of 5-bromobenzothiazoline, the structural formula is as follows:

[0039]

[0040] 0.5 mmol of raw material 5-bromobenzothiazole and catalysts yttrium bis(trimethylsilylamide) (0.1 equiv) and tris(pentafluorophenyl)borane (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacolborane (2.5 mmol), toluene (1.5 mL) were added, and the reaction was carried out at 50 °C for 12 h. The isolated yield of the product was 68%.

[0041] 1 H NMR (400 MHz, CDCl3) δ 6.91 (d, J = 8.1 Hz, 1H), 6.83 (dd, J = 8.1, 1.8 Hz, 1H), 6.75 (d, J = 1.8 Hz, 1H), 4.86 (s, 2H), 4.11 (brs, 1H); 13 C NMR (101 MHz, CDCl3) δ 149.0, 127.2, 123.5, 122.9, 118.3, 113.7, 53.4.

[0042] Example 4

[0043] Preparation of 2-(4-methoxyphenyl)-benzothiazoline, the structural formula is as follows:

[0044]

[0045] 0.5 mmol of raw material 2-(4-methoxyphenyl)benzothiazole and catalysts yttrium bis(trimethylsilylamide) (0.1 equiv) / tris(pentafluorophenyl)borane (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacolborane (2.5 mmol), toluene (1.5 mL) were added, and the reaction was carried out at 50 °C for 12 h. The isolated yield of the product was 89%.

[0046] 1 H NMR (400 MHz, CDCl3) δ 7.46 - 7.49 (m, 2H), 7.03 (ddd, J1 = 0.8 Hz, J2 = 7.6 Hz, J3 = 7.6 Hz, 1H), 6.93 (ddd, J1 = 0.8 Hz, J2 = 7.6 Hz, J3 = 7.6 Hz, 1H), 6.86 - 6.88 (m, 2H), 6.75 (ddd, J1 = 0.8 Hz, J2 = 7.6 Hz, J3 = 7.6 Hz, 1H), 6.63 (dd, J1 = 0.8 Hz, J2 = 7.6 Hz, 1H), 6.35 (s, 1H), 3.80 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 160.0, 146.2, 133.5, 128.0, 126.8, 125.4, 121.6, 120.6, 114.0, 109.7, 69.9, 55.3.

[0047] Example 5

[0048] Preparation of 2-propylbenzothiazoline, with the structural formula as follows:

[0049]

[0050] Add 0.5 mmol of the raw material 2-propylbenzothiazole and the catalyst yttrium bis(trimethylsilylamide) (0.1 equiv) / tris(pentafluorophenyl)borane (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacolborane (2.5 mmol), toluene (1.5 mL), and react at 50 °C for 12 hours. The isolated yield of the product is 88%.

[0051] 1 1H NMR (400 MHz, CDCl3) δ 7.05 - 7.07 (m, 1H), 6.90 (ddd, J1 = 0.8 Hz, J2 = 7.6 Hz, J3 = 7.6 Hz, 1H), 6.74 (ddd, J1 = 1.2 Hz, J2 = 7.6 Hz, J3 = 7.6 Hz, 1H), 6.65 (dd, J1 = 1.2 Hz, J2 = 7.6 Hz, 1H), 5.28 (t, J = 6.8 Hz, 1H), 1.84 - 1.92 (m, 2H), 1.41 - 1.51 (m, 2H), 0.96 (t, J = 7.6 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 146.5, 127.6, 125.1, 121.9, 120.9, 110.9, 68.5, 40.6, 19.3, 13.7.

[0052] Example 6

[0053] Preparation of 2-phenylbenzothiazoline, with the structural formula as follows:

[0054]

[0055] Add 0.5 mmol of the raw material 2-phenylbenzothiazole and the catalyst yttrium bis(trimethylsilylamide) (0.1 equiv) / tris(pentafluorophenyl)borane (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacolborane (2.5 mmol), toluene (1.5 mL), and react at 50 °C for 12 hours. The isolated yield of the product is 92%.

[0056] 11H NMR (400 MHz, CDCl3) δ 7.50 - 7.56 (m, 2H), 7.31 - 7.39 (m, 3H), 7.02 - 7.06 (m, 1H), 6.91 - 6.98 (m, 1H), 6.73 - 6.79 (m, 1H), 6.62 - 6.68 (m, 1H), 6.36 (s, 1H), 4.05 (brs, 1H); 13 13C NMR (100 MHz, CDCl3): δ 146.2, 141.6, 129.0, 128.8, 128.7, 126.6, 125.5, 121.6, 120.7, 109.8, 70.0.

[0057] Example 7

[0058] Preparation of 2-(β-naphthyl)-benzothiazoline, the structural formula is as follows:

[0059]

[0060] Add 0.5 mmol of the raw material 2-(β-naphthyl)-benzothiazole and the catalyst yttrium bis(trimethylsilylamide) (0.1 equiv) / borane tris(pentafluorophenyl) (0.1 equiv), p-trifluoromethylaniline (0.1 equiv), pinacol borane (2.5 mmol), toluene (1.5 mL), react at 50 °C for 12 hours, and the separation yield of the product is 95%.

[0061] 1 1H NMR (400 MHz, CDCl3) δ 7.81 - 7.88 (m, 4H), 7.73 - 7.75 (m, 1H), 7.48 - 7.50 (m, 2H), 7.07 (d, J = 7.6 Hz, 1H), 6.97 (dd, J1 = 7.6 Hz, J2 = 7.6 Hz, 1H), 6.78 (dd, J1 = 7.6 Hz, J2 = 7.6 Hz, 1H), 6.70 (d, J = 7.6 Hz, 1H), 6.56 (s, 1H); 13 13C NMR (101 MHz) δ 146.3, 138.8, 133.6, 133.0, 128.9, 128.1, 127.8, 126.6, 126.5, 126.4, 125.6, 125.4, 124.4, 121.7, 120.7, 109.8, 70.2.

[0062] Raw material list:

[0063]

[0064] The reaction equation of the present invention is:

[0065]

[0066] Through in-depth and meticulous research, the present inventor has discovered an efficient synthesis method for benzothiazoline compounds. Under the catalytic system of yttrium bis(trimethylsilylamide) / tris(pentafluorophenyl)borane, hydrogen transfer reduction reaction occurs to benzothiazole compounds, thereby realizing the synthesis of benzothiazoline with diverse structures. This method has wide sources of raw materials, simple operation, broad generality, and high selectivity. Compared with previous methods, its environmental friendliness and substrate generality have been significantly improved, which are difficult to achieve by other methods. The present invention has the following advantages and innovations:

[0067] (1) The reaction has good generality and high yield, and the yield of most reactions is above 80%;

[0068] (2) This is an important supplement to the preparation of benzothiazoline compounds and provides an important idea for the synthesis of bioactive compounds.

[0069] The beneficial effects of the present invention compared with the prior art:

[0070] The benzothiazoline prepared by the method of the present invention has high quality, high yield, good reaction generality, and convenient post-treatment, providing an important reference for the construction of benzothiazoline compounds.

[0071] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered by the scope of the claims of the present invention.

Claims

1. A method for synthesizing benzothiazoline, characterized in that: Under the co-catalysis of yttrium bis(trimethylsilyl)amide and tris(pentafluorophenyl)borane, an additive, a hydrogen source, and a benzothiazole compound react in a solvent to obtain a benzothiazoline compound; The structural formula of the benzothiazole compound is The structural formula of the benzothiazoline compound is The structural formula of the benzothiazole compound and the structural formula of the benzothiazoline compound, where R is hydrogen or 2-methyl or 5-bromo or 2-p-methoxyphenyl or 2-propyl or 2-phenyl or 2-β-naphthyl; The additive is p-trifluoromethylaniline; The hydrogen source is pinacolborane.

2. The method for synthesizing benzothiazoline according to claim 1, characterized in that: The solvent is toluene.

3. The method for synthesizing benzothiazoline according to claim 1, characterized in that: The reaction temperature is 50 °C and the reaction time is 12 h.

4. The method for synthesizing benzothiazoline according to claim 1, characterized in that: The molar ratio of the benzothiazole compound, yttrium bis(trimethylsilyl)amide, tris(pentafluorophenyl)borane, additive, and hydrogen source is 1.0:0.1:0.1:0.1:5.0.

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