CN103360339B - Green method for catalytically synthesizing 2'-aminobenzothiazolyl-arylmethyl-2-naphthol - Google Patents

Abstract

The invention provides a green catalytic method for synthesizing 2'-aminobenzothiazole-arylmethyl-2-naphthol, which belongs to the field of organic chemical synthesis. In the synthesis reaction, the molar ratio of aromatic aldehyde, 2-aminobenzothiazole and β-naphthol is 1:1:1, the molar amount of bissulfonate acidic ionic liquid catalyst is 5-8% of the aromatic aldehyde used, and the reaction temperature The temperature is 80～95℃, the reaction time is 3～10min, the volume of reaction solvent water (ml) is 3～5 times of the molar quantity of aromatic aldehyde (mmol), cool to room temperature after reaction, filter with suction, filter residue with 95% ethanol After recrystallization and vacuum drying, 2'-aminobenzothiazole-arylmethyl-2-naphthol was obtained. Compared with other synthetic methods, the present invention has the characteristics of high catalytic activity, less catalyst consumption, recyclable catalyst, less environmental pollution in the whole process, simple and convenient post-treatment, and the like.

Description

A kind of green catalytic method for synthesizing 2'-aminobenzothiazole-arylmethyl-2-naphthol

technical field

The invention belongs to the field of organic chemical synthesis, and in particular relates to a green catalytic method for synthesizing 2'-aminobenzothiazole-arylmethyl-2-naphthol.

Background technique

Heterocyclic compounds containing thiazole rings have broad-spectrum biological activities, can be used as local anesthetics, and have anticonvulsant, antiviral, antibacterial, insecticidal, anti-inflammatory and anti-allergic effects, and compounds containing aminothiazole rings have strong Physiologically active, it can be used to treat allergies, high blood pressure, osteoporosis, asthma, cancer, HIV virus, and also has a wide range of applications in cell biology. In addition, it is also a kind of good intermediate, and the amino functional group can undergo a series of reactions, and various compounds synthesized therefrom have a wide range of applications in medicine, pesticides, dyes, etc. Therefore, derivatives containing aminothiazole rings have always been concerned by medicinal chemists, and the research and development of drugs with such structures has important theoretical significance and practical value.

2′-Aminobenzothiazole-arylmethyl-2-naphthol is a very important compound containing aminothiazole ring derivatives, and its preparation has also become a research hotspot for organic synthesizers, especially for aromatic Study on the catalytic system used in the one-step synthesis of aldehydes, 2-aminobenzothiazole and β-naphthol. For example, in 2007, Shaabani et al reported the synthesis of 2′-aminobenzothiazole-arylmethyl-2-naphthol from aromatic aldehydes, 2-aminobenzothiazole and β-naphthol in aqueous medium using LiCl as a catalyst. The method has the advantages of green chemistry, but there are shortcomings such as long reaction time, large amount of catalyst, high price, and difficult recovery (Water promoted one-pot synthesis of2′-aminobenzothiazolomethyl naphthols and5-(2′-aminobenzothiazolomethyl)- hydroxyquinolines, Tetrahedron Letters, 2007, 48:7291-7294). Acidic ionic liquids, especially Bronster acidic ionic liquids, which are easy to prepare and stable to water and air, are green and pollution-free, have good solubility for organic and inorganic compounds, uniformly distributed acidic sites, and are easy to produce The advantages of separation and recycling are applied in the synthesis of 2'-aminobenzothiazole-arylmethyl-2-naphthol as a green catalyst. For example, Guo Hongyun et al. used ionic liquid [Hnmp]HSO ₄ (N-methylpyrrolidone bisulfate) as a catalyst to catalyze aromatic aldehydes, 2-aminobenzothiazole and β-naphthol under solvent-free conditions to synthesize a series of 2'-aminobenzothiazole-arylmethyl-2-naphthol, the method has mild reaction conditions, short reaction time, high yield and environmental friendliness. In addition, the catalyst can be recovered conveniently, and its catalytic activity is not significantly reduced after being recycled for four times (one-pot synthesis of 2′-aminobenzothiazole-arylmethyl-2 catalyzed by ionic liquid [Hnmp] _HSO4 under solvent-free conditions - Naphthol, Organic Chemistry, 2011, 51(1): 96-100).

The acidic ionic liquid adopted above is due to weak acidity, catalytic effect in the process of catalytic condensation of aromatic aldehydes, 2-aminobenzothiazole and β-naphthol to synthesize 2′-aminobenzothiazole-arylmethyl-2-naphthol It still needs to be improved, and the usage amount of ionic liquid is relatively large (accounting for 10% of the molar amount of aromatic aldehyde used). In addition, the loss of ionic liquid during recycling is also relatively large, and it can only be recycled 4 times. All of these make the process efficiency of the method low, and it is difficult to use it on a large scale in the industrial production of 2'-aminobenzothiazole-arylmethyl-2-naphthol.

Contents of the invention

The purpose of the present invention is to overcome the shortcoming that the amount of acidic ionic liquid catalyst used in the prior art and the amount of loss in recycling are very large, and provide a kind of reaction solvent with water, with the higher bissulfonate acid ion of acidity The liquid is used as a catalyst, and the green catalytic method for synthesizing 2′-aminobenzothiazole-arylmethyl-2-naphthol with high product purity and yield.

The structural formula of the disulfonic acidic ionic liquid catalyst used in the present invention is:

A kind of method of green catalytic synthesis 2'-aminobenzothiazole-arylmethyl-2-naphthol provided by the present invention, its reaction formula is:

Wherein the mol ratio of aromatic aldehyde (I), 2-aminobenzothiazole (II) and β-naphthol (III) in the reaction is 1:1:1, and the molar weight of bissulfonate acidic ionic liquid catalyst is used aromatic aldehyde The reaction temperature is 80-95°C, the reaction time is 3-10min, the volume (ml) of the reaction solvent water is 3-5 times the molar amount (mmol) of the aromatic aldehyde, and the reaction pressure is one atmosphere. Cool to room temperature after the reaction, filter with suction, recrystallize the filter residue with 95% ethanol, and dry in vacuo to obtain pure 2'-aminobenzothiazole-arylmethyl-2-naphthol (IV). The bissulfonate acidic ionic liquid catalyst and a small amount of unreacted raw materials contained in the filtrate can be reused without treatment.

The aromatic aldehyde (I) used in the present invention is benzaldehyde, 2-chlorobenzaldehyde, 4-chlorobenzaldehyde, 4-nitrobenzaldehyde, 4-methylbenzaldehyde, 4-methoxybenzaldehyde, 2-hydroxyl Any of benzaldehyde, 2-nitrobenzaldehyde, and 2,4-dichlorobenzaldehyde.

For the preparation method of the bissulfonate acidic ionic liquid catalyst used in the present invention, see related literature (Diastereoselective synthesis of pyrazolines using a bifunctional Brönsted acidic ionic liquid under solvent-free conditions. Advanced Synthesis & Catalysis, 354 (2012), 3095-3104).

The present invention has following characteristics compared with other acidic ionic liquids as the preparation method of catalyst:

1. The acidic ionic liquid containing disulfonate has high acid density, good catalytic activity and high catalytic yield;

2. Less catalyst usage and less loss during recycling;

3. Using water as the reaction solvent has little environmental pollution;

4. The post-treatment process is simple, and the catalyst can be recycled without any treatment.

Detailed ways

In order to describe the present invention more clearly, enumerate the following examples now, but the present invention is not limited to following examples, under the scope of not departing from before and after the stated purpose, any change implementation should be included in the protection scope of the present invention . EXAMPLES The reaction product was tested and characterized by nuclear magnetic resonance and infrared spectrometer, wherein Bruker AVANCE-II 500 MHz was used for ¹ H NMR, and NEXUS670 Fourier transform infrared spectrometer was used for IR.

Example 1

Add 1mmol of benzaldehyde, 1mmol of 2-aminobenzothiazole, 1mmol of β-naphthol, 3ml of water and 0.05mmol of bissulfonate acidic ionic liquid into a 25ml single-necked flask with a stirring bar and a reflux condenser. Stir vigorously at 80°C for 5 minutes, TLC (thin plate chromatography) detection, the raw material point disappears, cool to room temperature, and filter with suction, the obtained filter residue is recrystallized with 95% ethanol aqueous solution, and after vacuum drying, the pure product 2′-aminobenzothiazole is obtained -Phenylmethyl-2-naphthol, the yield is 94%. Add benzaldehyde, 2-aminobenzothiazole and β-naphthol directly to the filtrate for repeated use.

2′-Aminobenzothiazole-phenylmethyl-2-naphthol: ¹ H NMR (500MHz, DMSO-d ₆ ): δ=6.97～7.86(m, 16H, ArH/CH), 8.80(s, 1H , -NH-), 10.13(s, 1H, -OH); IR(KBr): ν=3379, 1623, 1595, 1544, 1518, 1445, 1332, 1270, 814 ^{, 750cm -1}

Example 2

Add 1mmol of 2-chlorobenzaldehyde, 1mmol of 2-aminobenzothiazole, 1mmol of β-naphthol, 5ml of water and 0.05mmol of bissulfonate acidic ionic liquid into a 25ml single-necked flask with a stirring bar and a reflux condenser. Vigorously stirred and reacted at 80°C for 4 minutes, detected by TLC (thin plate chromatography), the raw material point disappeared, cooled to room temperature, and filtered with suction, the obtained filter residue was recrystallized with 95% ethanol aqueous solution, and the pure product 2′-aminobenzothiazole was obtained after vacuum drying -(2-Chlorophenyl)methyl-2-naphthol, the yield is 95%. Directly add 2-chlorobenzaldehyde, 2-aminobenzothiazole and β-naphthol to the filtrate for repeated use.

2′-Aminobenzothiazole-(2-chlorophenyl)methyl-2-naphthol: ¹ H NMR (500MHz, DMSO-d ₆ ): δ=6.96～8.04 (m, 15H, ArH/CH), 8.82(s, 1H, -NH-), 9.91(s, 1H, -OH); IR(KBr): ν=3384, 1628, 1597, 1543, 1440, 1319, 1271, ^{815, 754cm -1}

Example 3

Add 1mmol of 4-nitrobenzaldehyde, 1mmol of 2-aminobenzothiazole, 1mmol of β-naphthol, 5ml of water and 0.05mmol of bissulfonate acidic ionic liquid into a 25ml single-necked flask with a stirring bar and a reflux condenser. Vigorously stirred and reacted at 85°C for 3.5 minutes, detected by TLC (thin plate chromatography), the raw material point disappeared, cooled to room temperature, and filtered with suction, the obtained filter residue was recrystallized with 95% ethanol aqueous solution, and after vacuum drying, the pure product 2′-aminobenzo Thiazole-(4-nitrophenyl)methyl-2-naphthol, yield 96%. Directly add 4-nitrobenzaldehyde, 2-aminobenzothiazole and β-naphthol to the filtrate for repeated use.

2′-Aminobenzothiazole-(4-nitrophenyl)methyl-2-naphthol: ¹ H NMR (500MHz, DMSO-d ₆ ): δ=7.06～8.14(m, 15H, ArH/CH) , 8.92(s, 1H, -NH-), 10.21(s, 1H, -OH); IR(KBr): ν=3393, 1626, 1599, 1534, 1443, 1349, 1270, 813 ^{, 753cm -1}

Example 4

Add 1mmol of 4-methylbenzaldehyde, 1mmol of 2-aminobenzothiazole, 1mmol of β-naphthol, 4ml of water and 0.05mmol of bissulfonate acidic ionic liquid into a 25ml single-necked flask with a stirring bar and a reflux condenser. Vigorously stirred and reacted at 80°C for 3 minutes, detected by TLC (thin plate chromatography), the raw material point disappeared, cooled to room temperature, and filtered with suction, the obtained filter residue was recrystallized with 95% ethanol aqueous solution, and vacuum dried to obtain the pure product 2'-aminobenzothiazole -(4-methylphenyl)methyl-2-naphthol, the yield is 96%. Directly add 4-methylbenzaldehyde, 2-aminobenzothiazole and β-naphthol to the filtrate for repeated use.

2′-Aminobenzothiazole-(4-methylphenyl)methyl-2-naphthol: ¹ H NMR (500MHz, DMSO-d ₆ ): δ=2.22(s, 3H, -CH ₃ ), 6.98 ～7.84(m, 15H, ArH/CH), 8.76(s, 1H, -NH-), 10.11(s, 1H, -OH); IR(KBr): ν=3373, 1629, 1595, 1541, 1453, 1336, 1273, 1204 ^{, 815, 750cm-1}

Example 5

Add 1mmol of 4-methoxybenzaldehyde, 1mmol of 2-aminobenzothiazole, 1mmol of β-naphthol, 4ml of water and 0.08mmol of bissulfonate acidic ionic liquid into a 25ml single-necked flask with a stirring bar and a reflux condenser. Vigorously stirred and reacted at 90°C for 5 minutes, detected by TLC (thin plate chromatography), the raw material point disappeared, cooled to room temperature, and filtered with suction, the resulting filter residue was recrystallized with 95% ethanol aqueous solution, and vacuum dried to obtain the pure product 2'-aminobenzothiazole -(4-methoxyphenyl)methyl-2-naphthol, yield 95%. Directly add 4-methoxybenzaldehyde, 2-aminobenzothiazole and β-naphthol to the filtrate for repeated use.

2′-Aminobenzothiazole-(4-methoxyphenyl)methyl-2-naphthol: ¹ H NMR (500MHz, DMSO-d ₆ ): δ=3.67 (s, 3H, -OCH ₃ ), 6.85～7.92(m, 15H, ArH/CH), 8.78(s, 1H, -NH-), 10.13(s, 1H, -OH); IR(KBr): ν=3374, 1626, 1598, 1542, 1510 , 1451, 1256, 1173 ^{, 818, 752cm-1}

Example 6

Add 1mmol of 2,4-dichlorobenzaldehyde, 1mmol of 2-aminobenzothiazole, 1mmol of β-naphthol, 5ml of water and 0.08mmol of bissulfonate acidic ionic liquid into a 25ml one-necked flask with a stirring bar and a reflux condenser. Vigorously stir the reaction at 90°C for 10 minutes, TLC (thin plate chromatography) detection, the raw material point disappears, cool to room temperature, and filter with suction, the obtained filter residue is recrystallized with 95% ethanol aqueous solution, and the pure product 2'-aminobenzothiazole is obtained after vacuum drying -(2,4-dichlorophenyl)methyl-2-naphthol, the yield is 94%. Directly add 2,4-dichlorobenzaldehyde, 2-aminobenzothiazole and β-naphthol to the filtrate for repeated use.

2′-Aminobenzothiazole-(2,4-dichlorophenyl)methyl-2-naphthol: ¹ H NMR (500MHz, DMSO-d ₆ ): δ=6.98～8.04(m, 14H, ArH/ CH), 8.88(s, 1H, -NH-), 9.93(s, 1H, -OH); IR(KBr): ν=3379, 1627, 1596, 1540, 1470, 1454, 1268, 816, 751, 687cm ^-1

Example 7

Taking Example 1 as the probe reaction, the activity repeatability test of the reaction catalyst bissulfonate acidic ionic liquid was used, and the ionic liquid was reused 5 times. The yield data of the reaction are shown in Table 1.

The catalyst activity repeatability test result that table 1 the present invention uses

Disulfonate acidic ionic liquid use times Yield(%) 1 94 2 92 3 91 4 91 5 90 6 88

Can draw such a conclusion by table 1 data: the productive rate of catalyzer 2 '-aminobenzothiazole-phenylmethyl-2-naphthol reduces slightly in the recycling process, but the magnitude of reduction is small, proves that it can It is recycled in the preparation of 2'-aminobenzothiazole-arylmethyl-2-naphthol.

Claims (2)

1. the method for green catalysis synthesis 2 '-aminobenzothiazole-arylmethyl-beta naphthal, wherein synthesize aromatic aldehyde in the reaction of 2 '-aminobenzothiazole-arylmethyl-beta naphthal, the mol ratio of 2-aminobenzothiazole and 2-Naphthol is 1:1:1, the molar weight of disulfonic acid root acidic ionic liquid catalysts is 5 ~ 8% of aromatic aldehyde used, temperature of reaction is 80 ~ 95 DEG C, reaction times is 3 ~ 10min, be with 3 ~ 5 times of the aromatic aldehyde amount of mmole gauge in the volume of the reaction solvent water of milliliter, reaction pressure is a normal atmosphere, room temperature is cooled to after reaction, suction filtration, filter residue 95% ethyl alcohol recrystallization, pure 2 '-aminobenzothiazole-arylmethyl-beta naphthal is obtained after vacuum-drying,

Described aromatic aldehyde is any one in phenyl aldehyde, 2-chlorobenzaldehyde, 4-chlorobenzaldehyde, 4-nitrobenzaldehyde, 4-tolyl aldehyde, 4-methoxybenzaldehyde, Benzaldehyde,2-hydroxy, 2-nitrobenzaldehyde and 2,4 dichloro benzene formaldehyde;

The structural formula of described disulfonic acid root acidic ionic liquid catalysts is:

2. the method for a kind of green catalysis synthesis 2 '-aminobenzothiazole-arylmethyl-beta naphthal as claimed in claim 1, it is characterized in that, the disulfonic acid root acidic ionic liquid catalysts contained in filtrate after described suction filtration can not treatedly be reused.