Application of 4-ethyl phenyl isothiocyanate_Kain Industrial Additive

Overview^[1][2]

4-Ethylphenylisothiocyanate is an organic intermediate that can be prepared from 4-ethylaniline and can be used to prepare thiazolidine or thiourea structures.

Apply^[1-2]

1. Used to prepare a compound with a thiazolidine structure.

Add 0.1mmol benzylamine, 0.1mmol phenyl ethyl isothiocyanate, 0.3mmol ethyl 2-bromoacetate, 0.4mmol sodium hydroxide, and 1ml acetonitrile into the reaction tube, and illuminate it with a 465nm light source , stir and react for 12 hours. After the reaction is completed, it is separated and purified by column chromatography. The volume ratio of petroleum ether and ethyl acetate in the column chromatography eluent is 5:1. The purified target product is obtained with a yield of 90% and a purity of 99.8%.

The structure of the obtained product was characterized. The hydrogen NMR spectrum and the carbon NMR spectrum are shown in Figure 21 and Figure 22 respectively. The structural characterization data are as follows:

¹HNMR (400MHz, CDCl₃): δ=7.51-7.49 (d, J=7.1Hz, 2H), δ=7.32-7.24 (m, 3H), δ = 7.16-7.14 (d, J = 8.1Hz, 2H), δ = 6.88-6.86 (d, J = 7.9Hz, 2H), δ = 4.99 (s, 2H), δ = 3.72 (s, 2H), δ=2.64-2.59 (q, J=7.6Hz, 2H), δ=1.24-1.20 (t, J=7.6Hz, 3H).

¹³CNMR (100MHz, CDCl₃): δ=171.6,153.5,145.5,140.6,136.1,129.1,128.6, 128.5,127.9,120.9,46.2, 32.7,28.4,15.6.

MS (EI, 70eV): m/z (%) = 310.1 (M⁺), 268.1, 236.2, 207.1, 165.1, 148.1, 131.1, 105.1, 91.1, 65.1.

2. Used in the preparation of thiourea

Preparation of 1-(3-(((6,7-difluoroquinoxalin-2-yl)amino)methyl)phenyl)-3-(4-ethylphenyl)thiourea:

At room temperature, stir 5.5 mmol of glyoxylic acid and 5 mmol of 4,5-difluoro-phenylenediamine in ethanol for 4 hours (TLC detects the reaction progress). After the reaction is completed, distill under reduced pressure. Spin dry and separate by fast silica gel column chromatography (petroleumEther:ethyl acetate=2:1) to obtain the product 6,7-difluoroquinoxalin-2(1H)-one;

Add 5 mmol of 6,7-difluoroquinoxalin-2(1H)-one to 10 mL of phosphorus oxychloride, and reflux for 2 hours at 120°C. After the reaction is completed, pour the reaction mixture into Pour into ice water, wait until unreacted phosphorus oxychloride reacts completely with water, extract with ethyl acetate, take the organic phase, distill under reduced pressure, and separate by silica gel column chromatography (petroleum ether:ethyl acetate=10: 1), obtain purified 2-chloro-6,7-difluoroquinoxaline;

Add 2mmol of 2-chloro-6,7-difluoroquinoxaline, 2.2mmol of 3-aminobenzylamine and 2.4mmol of triethylamine into the isopropyl alcohol solution, and the mixture was refluxed at 120°C. 6h, after the reaction is completed, perform flash silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain purified N-(3-aminobenzyl)-2-amine-6,7-difluoroquine oxaline;

Dissolve 1 mmol of N-(3-aminobenzyl)-2-amine-6,7-difluoroquinoxaline in 1,2-dichloroethane, add 1 mmol of triethylamine dropwise, and then 1 mmol of 4-ethyl phenyl isothiocyanate was added, and the mixture reacted at room temperature overnight (TLC monitored the reaction). After the reaction was completed, it was subjected to flash silica gel column chromatography (petroleum ether: ethyl acetate = 2:1). Purified 1-(3-(((6,7-difluoroquinoxalin-2-yl)amino)methyl)phenyl)-3-(4-ethylphenyl)thiourea is obtained. The characterization data of compound o (melting point, hydrogen nuclear magnetic spectrum, carbon spectrum and high-resolution mass spectrum) are as follows:

m.p.121-123℃;¹H NMR (400MHz, DMSO-d6):δ9.69(s,1H),8.39(s,1H), 8.29(s,1H),7.80(dd,J＝ 11.0,8.8Hz,1H),7.60-7.36(m,2H),7.40-7.23(m,2H),7.15(m,2H),4.62(d, J＝5.0Hz, 1H), 2.56(m,1H),1.17(m,2H)ppm;

¹³C NMR (100MHz, DMSO-d6):δ180.0,152.9,150.3,148.4,145.9,140.7,140.5, 140.1,139.9,139.8,139.7, 137.4,133.1,128.8,128.2,124.4,124.0,122.8,115.4, 112.3ppm; HRMS(m/z)(ESI):calcd for C24H22F2N5OS[M+H]⁺:450.1558; found: 450.1555.