UA78077C2 - Method for obtaining 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazoline-4-on - Google Patents

Abstract

The invention relates to organic chemistry, in particular to a process for synthesis of 3-amino-2-thioxo-1,2,3,4-tetrahydroquinozaline-4-on, which is used as original product for the synthesis of different heterocyclic compounds, in particular such to which a high physiological activity is inherent. A process for obtaining analytically pure 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazoline-4-on consists in addition of methanol solution of methyl-2-isothiocyanobemzoate in mixing for 30 min till methanol solution of double amount of hydrazine monohydrate at the temperature of 5-10 DEGREE C, conditioning the reaction mass for 30 min at 20 DEGREE C and filtration of product. The yield of 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazoline-4-on is 95-97% on basis of initial methyl-2-isothiocyanatobenzoate, the temperature of melting is of 255-257 DEGREE C.

Description

Description of the invention

The invention relates to organic chemistry, to a new method of synthesis of 2Z-amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one, which is used as an intermediate product for the synthesis of physiologically active heterocyclic compounds that can be used in pharmaceuticals and medicine.

The following methods of synthesis of 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one are known: 1) decomposition of 2-phenyl-2,3-dihydro-5H-1,3,4-thiadiazolo|2 ,3-B|quinozolin-b-one with an aqueous solution of sodium hydroxide, yield of the target product 4095 11; 70 2) hydrolysis of 3-acetylamino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one with hydrochloric acid, yield of the target product 70905 (21; 3) hydrazinolysis of methyl 2-(methyldithiocarbamino)aminobenzoate, yield of the target product 4390 |ZI; 4) interaction of anthranilic acid hydrazide with carbon disulfide in an alkaline environment, yield of the target product 7390 |4, 51; 12 5) thermal isomerization of 5-(2-aminophenyl)-2,3-dihydro-1,3,4-oxadiazole-2-thione, yield of the target product 9490 µl;

But all these methods do not allow synthesizing 3-amino-2-thioxo-1,2,3,4-tetrahydro-quinazolin-4-one with a high yield and in an analytically pure form from available starting materials.

The closest to our claimed method in terms of substance and result is the method based on the reaction of methyl-2-isothiocyanatobenzoate with an equimolar amount of anhydrous hydrazine in dry diethyl ether 71.

The peculiarity of this method is that an emulsion of hydrazine in diethyl ether is added dropwise to a solution of methyl-2-isothiocyanatobenzoate in diethyl ether, the reaction mixture is kept for 3 h at 2022 and the target product is obtained with a yield of 8895 (product m.p. 210-2202С) . We chose this method as a prototype. The disadvantages of this method are that dry diethyl ether and anhydrous hydrazine are expensive, difficult to obtain, highly flammable and explosive reagents, and the target product, even after recrystallization from methanol, is not analytically pure and contains impurities (e.g. recrystallized from methanol product 227-2302С).

The task of the invention is to develop a method of synthesis of analytically pure

of z-amino-2-thi-oxo-1,2,3,4-tetrahydroquinazolin-4-one in quantitative yield, which is based on available chemical reagents and fire- and explosion-proof solvents, based on an improved method |71.

The task is solved by adding a methanol solution drop by drop. of methyl-2-isothiocyanatobenzoate to a methanolic solution of twice the amount of hydrazine monohydrate and holding for a reaction mass of O0.bBh at 209C. This order of mixing reagents, as well as a double excess of hydrazine monohydrate suppresses the competitive reaction of 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one with so methyl-2-isothiocyanatobenzoate, which contributes to the formation of pure target product. The method proposed by us makes it possible to synthesize analytically pure (without additional recrystallization)

Z-amino-2-thuxo-1,2,3,4-tetrahydroquinazolin-4-one (m.p. 255-2572C) with quantitative yield (95-97905). In addition, this method is more acceptable from the point of view of safety and availability of starting reagents. "

OO

WITH -

I hear from MB. MN, i» | pan odon A -4 soosn, with Mm' 78

N

Example o Synthesis of 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one.

A solution of 1.93 g (0.01 mol) methyl-2-isothiocyanatobenzoate in 1 mol of methanol is added dropwise to a solution of 1.0 g (0.02 mol) of hydrazine monohydrate in 1 mol of methanol while stirring at a temperature of 5-1090 o for 0.5 hours. -I 20 Stir for 0.Bh at 202С, filter off the precipitate and dry. Yield 1.83-1.87 g (95-97905), temp. 255-25726.

Calculated, 905: C 49.73, H 3.65, M 21.75, 5 16.59. SeNUM3O5. Found, Uo: C 50.01, H 3.58, M 21.54, 5 16.73. tm NMR spectrum of "H (DMSO-dyb, 5, ppm, Hz): 6.40 (2Н, с, МН»), 7.23 (1Н, т, ндг, 9-7.2), 7.34 (1Н, d, нд . dv, 5, m.d.): 115.8 (С-47), 11941

B (Sdg), 123.1 (Sdg), 126.2 (sa), 133.8 (sdg), 141.9 (C-87), 155.9 (C-0), 169.5 (C-8). IR spectrum (in, cm", KVh): 3300, 3200, 1695 (C-0), 1650, 1570, 1495, 1440, 1410. o The method we developed for the synthesis of analytically pure 3-amino-2-thioxo-1, 2,3,4-tetrahydroquinazolin-4-one is economically and technologically more feasible than all other methods described in the literature, and may find use in the chemical and pharmaceutical industry. 60 References 1. Modi 5.K., Saknag N.K. ., Magapa K.5. // dpaiap. U. Spet. -1970. - 8 (5). - R. 389-390. 2. Bakpnag N.K., Syria 5.K., Kyptag M. // dpaiap. 9. Spet. - 1981. - 208 (1). - R. 14-16. 3. Rainak 0.5., Oemapi M.M., Zpizpoo S.., KyiKagpi K.K // dpaiap. 9. Spet - 1986. - 258 (5). - R. 489-491. 4. Pi K.SN., Ni M.K. // Agei. rpapt. - 1987. - 320 (2). - R. 166- 171. 65 5. Pi KSV. Ni M.K., ip o 0.0. / Spipd-pip Mao Nviei Tva Spiiy. - 1990. - 42 (1). - R.83-89; Spet.

Arzig - 1991. - 114 - 2391 ON.

6. Rusu G.G., Koval D., Gutsu Y.E., Barba N.A. //ChGS. - 1995. - 7. - P.1000-1001. 7. Spegritsieg E., UMiINa!t V., Dassaga 5., Kabripomiikh .). // Neimeyisa Spit.

Asia - 1967. - 50 (8). - R. 2563-2569.

Claims (1)

2 Formula of the invention Method of obtaining analytically pure 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one of the general formula (1) o () 70 sh MN. MM 5 H based on the interaction of methyl-2-isothiocyanatobenzoate with hydrazine monohydrate, which differs in that methyl-2-isothiocyanatobenzoate is added to twice the amount of hydrazine monohydrate in methanol and the reaction mass is kept for 0.5 hours. Official bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated microcircuits", 2007, M 2, 15.02.2007. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. s io) cha yich- "c) s i - "no s i" -I (ee) ("c) - 50 what F) has) 60 b5