SU1095583A1 - 3-nitro-4-aminophenyl-/20(alcoxycarbonyl)-phenyl/-methanons as initial products in synthesis of phthalobendasol - Google Patents

Abstract

Nitro-4-aminophenyl- 2- (alkoxycarbonyl) Lenyl-methanones of the formula O C-Ch-y-NH2 COOAlk CO where Alk is alkyl C, as initial products in the synthesis of the anthelminthic drug phthalbendazole „Lncnosomes” Nearest to the target (L compounds of formula I are phenyl (3-nitro-4-aminophenyl) methanones. However, up to the present time,

Description

to be used in the synthesis of the drug phthalbendazolao. The goal is to attain the new 3-nitro-4-aminophenyl-2-alkoxycarbonyl) phenyl 2-methane of the above formula I, which can be obtained from 3-nitro-4-chloro. benzophenone-2-carboxylic acid of formula II O NOi by reacting with an alcohol of the general formula Alk-OH, where Alk has the indicated values, in the presence of sulfuric acid at the boiling point of the reaction mixture and the resulting (3-nitro-A-chlorofesh) 2- (alkoxycarbonyl) fensh11 methanones of the general formula III L - and -TVce COOAIK NOg where Alk has the indicated values, is reacted with gaseous ammonia in dimethyl oxide, dimethylformamide or ethylene glycol at elevated temperature, preferably at a temperature of from 50 to 150 C followed by vyd The target compounds of the formula I are isolated in an analytically pure form, they are bright yellow ... crystalline products, well soluble in acetic acid and dimethylformamide, sparingly soluble in alcohols, dioxane, benzene and toluene and practically insoluble in water Example me “Preparation of (3-nitp6-4-chlorophenyl) 2- (isopropoxycarbonyl) -phenshP-methanone. A mixture of 50 g of 3-nitro-4-chlorobenzophenone-2-carboxylic acid, 250 ml of absolute isopropyl alcohol and 25 ml of concentrated sulfuric acid (d 1.84) (boil under reflux to form a solution (h), mountains the solution is filtered, the precipitate formed after cooling is separated, washed successively with water, 10% aqueous sodium carbonate solution and again with water, dried in air to give 40.0 g of a light gray product, after recrystallization from isoprosh alcohol with ToPlo113-114, Example 2o Preparation (3-nitro4-aminophene l) (2-isopropoxycarbonyl) phenyl-methanoneo To a solution of 24.6 g of (3-nitro: 4-chlorophenyl) (2-isopropoxycarbonyl) phenyl-methanoia in 150 ml of dimethyl sulfoxide with ultrasound-BOC are bubbled gaseous ammonia for 4 6 hours until the starting material disappeared in the reaction mixture (monitored by TLC on Silufol plate, benzene alcohol system (23: 3), detection with UV light). At the end of the reaction, the mass was diluted with 50 ml of isopropanol, poured into 600 ml of cold water and leave overnight in a refrigerator. The separated crystals are separated, washed with water and dried at 80-90 St Paul 20.0 g () of the target substance in the form of bright yellow crystals with ToPL of 135.5137 ° C, Example 3, are prepared. Analogously to Example 1, compounds of the formula III are obtained from 3-nitro-4-chlorobenzophenone-2carboxylic acid and the corresponding alcohol where Alk is methyl, ethyl, propyl and n, butyl (look-up) o. Example 4 Analogously to Example 2, the corresponding (3-nitro-4-amino-phenyl) methanones of formula III give the desired compounds of formula 1 where Alk is methyl, ethyl, propyl and n butyl o. Pr and m in p 5o Obtaining (3-nitro4-aminofensh1) 2- (methoxycarbonyl) fenshG | -methanone "In a solution of 10.0 g (0.0327 mol) 2 (3-nitro-4-chlorobenzoyl) benzoic acid in 100 Mii of dimethyl sulfoxide with ammonia gas was bubbled until the starting material disappeared in the reaction mass (TLC monitoring on the Silufol plate in the system isopropyl alcohol — 25% aqueous ammonia solution, taken in a 10: 1 ratio), the source material disappears after 8 hours and is a new substance with a Pf of 0.34 (detected by UV light). At the end of the reaction, the reaction mass is poured into 250 ml. odes, the precipitate is separated, washed with 10% hydrochloric acid and water until neutral and dried at 7.8 g of a yellow substance, which is 2- (3-nitro-4-aminobenzoip) benzoic ACID;

6 g of 2 (3-nitro-4-aminobenzoyl benzoic acid is boiled in 50 MP of methanol with 2 ml of concentrated sulfuric acid for 6 hours, 2/3 of methanol is distilled off and the residue is taken up in 200 ml of 5% aqueous ammonia solution, the precipitated precipitate separated, dried and crystallized from methanol, yielding 4.2 g of bright yellow crystals (3-nitro-4-aminophenyl) 2- (methoxycarbonyl) -phenip-methanone with Topl 180-182 s,

An example of the use of described source materials for the synthesis of the drug Phthalbendazole. is given; on the diagram

Stage i

NHa-NHg-HgO

The claimed starting materials of the formula I are Cgoli / t L / Ke, H2 O DMF, the preparation Phtalbendazol (G tl “w CSCCO 2 HjCS-C-NHCOzCHg LcnsOn, II35)

The advantages of using (3-nitro4-aminophenyl) 2- (alkoxycarbonsh1) phenyl 3-methanones as starting material:

a) easy availability of the starting material-4-chloro-3-nitrobenzoyl-2-benzoic acid II

b) the possibility of synthesizing the described starting materials according to a scheme whose processes do not require special equipment and reagents (for example, autoclaves or the use of highly toxic raw materials), but can be obtained in

conventional reactors at temperatures 45 not exceeding 100s

COgH N02

the column ana ie indicates the elements for which the microanalysis was performed; found the values did not differ by ± from the theoretical values, b - recrystallized the day of analysis from methanol, c - from strth, d - from isopropanol

Claims (1)

Formula СООА1К 'NO 2 ABOUT Oh-MF ⁷ Um 'SOD1K N0 ₂ j Aik CH _{3 g} ^ c n _e n _z -n C ₃ H ₇ -iso C ₄ H, C ₄ -H -iso ^ H Chj CjHjΟ, Ηγ-Η C ₃ H ₇ -iso C ₄ H ₄ -H C ₄ H ₉ -iso Exit, Z T.pLo, ° C Analysis 80 121-.122 ^8, 98-100 \ C1 83 C1 80 55-56-b C1 85 113-114.5 C1 85 oil _β C1 75 85.5-86.5 G C1 67 180-182 _g Chn 70 157-158.5 Chn 75 138-140®. Chn 90 135.5-137 Chn 60 99-101 ^g .v Chn .78 131-133 Chn α а - in the column `` analysis' ¹ the elements are indicated for which microanalysis was made} the found values did not differ by + 0.4% from the theoretical values, b - recrystallized for analysis from methanol,. c - from alcohol, g - from isopropanol.