SU667548A1 - Method of producing 2-amino-or 2-methyl amino-5-chloro-benzophenol - Google Patents

Description

Veduga process in the presence of causal amounts of acetic acid.

The recovery of 5-chloro-3-phenyl-tanranil with iron powder takes 3.5 hours in water. The resulting amineOkegon is practically insoluble in water and it is extracted from organic oxides that are mixed with water (benzene, toluene, etc.). .) After uparn solvent vydl rg 2-amyno-5-x 1 orbenzdfenon with the content of the basic substance of 90-97% (depending on the purity anthranil). After recrystallization from 70% isopropyl alcohol, an ammo is obtained & with a yield of 87-90% to the starting anthranyl with the content of the main substance not less than 98.5%. More than 3-5% of the ms amino ketone is derived from the queen cells.

Much more convenient is the weight recovery in aqueous alcohols, in particular, in 7O% ethyl or isoprop in oats and alcohols. In one case, the operation of recovery of intrinsic, excretion and o4HctKH of amino ketone ss emigenes — after reconstitution, the hot solution of amiokegon is filtered from the sludge and cooled, and 87-88% of 2-amino-5-chlorobenzrpheno a falls out of the cooled solution; The main substance is more than 99%. In addition, 3-5% of pure amyiketone can be isolated from machy; The total yield of high-quality amino ketone is 9O-93% and the "similar S-chloro-3-4 enyl ylate {an} 1.

2 -M e-hilamino-5-chloro-zofvnon is formed by & sedimentation of megyl sulfate with 1-methyl-S-chloro-3-phenylangranyl, and the reduction is also carried out with iron hearth in a siyrgzho-eighth medium. The 5-chloro-3-phenyl-antenil HGH-salt is prepared by reacting anthranyl with dimethyl sulfate in toluene at 9O-10O®C {per 1 M anthranyl, taking 1.5 M dimethyl sulfate precipitated salt from 4ltrove {0 and washing on the filter with Dichloroethane. During the washing, the salt is washed away from the resinous impurities, unreacted anthranil and 1H) luol. Without additional drying, h: etheretichy salt is dissolved on the filter in SO-5O% - isopropyl and ethyl alcohols, the resulting solution is added to the suspension of the iron powder in water, activated by electrolyte treatment, for example, with acetic acid ammonium chloride, and lead recovery in the usual way. The presence of small amounts of anthranil in the salt: dichloroethane does not interfere with the recovery process and the release of the product. If dichloroethane is different, which is easily determined by lowering the boiling temperature of the plant, then, to facilitate subsequent release of the amyocoeton, dichloroethane is removed from the reaction by conventional distillation. At the end of vsstanstvleni Myssu, cool the precipitate to 2 o G and heat it up and extract it with 2-megylamino-5-chlorobenzophenone by washing with a slurry, or naryk yer benzene, carbon tetrachloride, dichloroethane. The solvent is distilled off and get

amine ketone with a yield of 82–85% on 5-chloro-3-enyl-anthranil (in terms of 100% of the substance) with a content of the basic substance (purity is determined spectrophotometrically) not less than 97%.

reduction is determined by special experiments on the reduction of dry salt and is 95-97%.

According to another version of the suspension “Quaternary salt in toluene after | Tilirovanie anuranyl is added to ZO% iso-optic alcohol, the organic layer is separated, the aqueous-alcoholic solution is washed with toluene and dichloroethane and reduced with iron powder in water in the presence of an electrolyte. The yield of 2-4 egilami no-5-chlorobenzene is equal to 80-85% under these conditions.

The recovery of the quaternary 5-oshor-3-phenyl 1granyl is easily passed in the vrp and in more KOHueHTpHpoBamibtx alcohols (the yield on recovery is also 9597%). However, pactaopHMocTb salts in water and in 60-70% aqueous alcohols are significantly lower than in ZO-BOO% isopropyl and ethyl alcohols, which makes it difficult to use a salt solution in the reduction.

2-Methylamino-5-chl orbenzophenone obtained by the proposed method, the dosga is precisely pure; it contains only traces of an amino ketone without a methyl group. In the synthesis, it is possible to use technical anganil with cp holding the main weight of 90-95-%, 1 fi - is the yield (per 100% anthranil) and the quality of the aminokete is practically not reduced.

A solution of 2g yutylamine (α-chlorobenzophenone can be used without isolation of the amino ketone for chloroacetylation (nanfimer, in the production of dyaseyam, medazepam).

Using the Preferred | of the invention makes it possible to significantly simplify the process of obtaining 2-amino- or 2-child aMHHorS-chlorobenzophenone for the time base {HCnonbaoBiaiHHH score with the resumption of technical 5-chloroanthanum a. With the use of technical anthranil with a content of the main substance of 90%, the output of 2 mine-5-chlorobenzophenone remains practically unchanged {in terms of the lOO-base anthranil), and its purity is 98.5-99%; Only when using anthranil of very high quality (purity 7–4–7 b%), the penetration rate of the noycetone falls to 70–7–2%, and contains up to 96–97%. In addition, the proposed method allows the production of 2-chylethylamine 5-chlorobene-phenanone from 60 to 8.5% -: - - -; - - - - - - - - -: -. -. to the advantages of the proposed method of producing 2-amino- and 2-methylamino -5-. - Dorbyonzofenons should be taken out of all major waste water. zhee salts are easily removed from the solution when they are treated with the main agents (when reconstituted in alcohols, salt is filtered by the filter in combination with the salt (iron) in water, in water; and in the middle of anostometry, it is not yourself. of the process in 70% of the LOWER syyrtykh they are removed from the mother liquor in the usual way.; P I M i IP 1. Reconstruction 5-chloro-ferric iron powder: W.W. powder.::: -.;. . :: In a Tpexixjfinyio flask of 250 ml AND ;-;: with a bottle,: 1; 4 hanger and TepMOMerpoN primer: CT 20 g (by 1OO% - e substance 5-chloro-phenyl-anthrac) 1a anil is 9 (3%), 4 g of riopoHika PZh4M zhyozyvzhygr, 10O dd, and 1 ml of 98% acetic acid. The mass is heated 11 yo and sivey at this temperature content isoMal aral sodium in meee O, 1 % (xpOMaT6rpa “| H“ 4eckHft Reactant gas 4), Oh h. At the eye. The mass of the cooling mass is cooled to .G, filtered and washed at 150 ml roi r black (60-7 ° C) benzene or toluene. The combined extracts are evaporated under vacuum or at atmospheric pressure in half a mass of 2-amyo-5-chloro-en-eopheion, which crystallizes upon standing for 6-6 | | E, by the basic substance, 9097% (depending on the purity of the ethereal); Him. Percrystallization of 7 ppm, 7O% ooperopropyl alcohol and a total of 17.8-18.4 g of 2-amino-5-chlorobeisophenone with a purity of 98.5-99, mp. 95 " . When the mother liquors are evaporated in the recrystallization of OCTaTisfa from 85% isopropyl alcohol, 0.4-0.6 g of aminrketone with a purity of 98.5- is additionally obtained. 99%. In total, 18.2-18.8 g of 2-amino-5-zslorbenzofenone with a content of 98.599, 5% or 18.1-18.5 g of substance are obtained. The output is 90-92% of the original. Example 2. Recovery 5-. -chloro-3-phenyl-anthramine: in 7O% isopropyl alcohol. A 250 ml three-necked flask with a fridge, a stirrer and a thermometer loads 20 g (0.087 mol) in terms of 100% 5-chloro-3gphenyl-anthranil, 4 g of iron powder SHK4M, 10 O ml of 70% g "isopropyl alcohol and 1 ml of 9% acetic acid. Macicy is boiled down to a boiling point (83) and kept at this temperature until the starting anthranil is present in a mass of more than 0.1%. The reaction takes 3–4 hours; At the end of the reaction, 2 g of activated carbon is added to the mass, stirred at boiling for 15-2 minutes and filtered on a Bopcstke for hot filtration. The wasp of the drug on the filter was washed with 10-15 ml of 85% isopropyl alcohol and washed. The CIs are attached to the main filtrate, the solution is cooled to a value of 0-2.c, holding at this temperature for 2 hours and 2i-aMHHO-5-chlorobenzophenone is filtered off. This gives 17.8-1 lO / g amine-chain with a purity of 98.5-99.5% and so on. Eb-EZ C. In case of evaporation and the recrystallization of the residue from 85% isopropyl alcohol, an additional amount of O, 6–1 g of amino-acid with a purity of 98.5-99.5% is obtained. A total of 18.2–19; 0 g of 2-amino-5-chloorbenzrfenone with a content of .98.5 100% Nbgo®® or 18.1-18.7 g is 90-93% stroke for PF. and measure 3. Receiving2 ... megilamy-n6-5-chlorobenzophenry. A 250-ml flask with a stirrer, a reflux condenser, a dropping funnel and a thermometer is charged with 23 g (Oil mole) in terms of 100%. The substance is 5-chloro-3-phenyl-anthranil, 32 ml of toluene and 14.2 ml (18.9 g; 1.5 mol) of dimethyl sulfate are poured at 60 ° C. The temperature in mass raises up to y. is maintained at 90–10 ° C from 3 h. At the shutter speed, the mass is diluted with 40 ml of toluene, the precipitate is filtered off and washed on the filter with 100 ml of dichloroethane. Then, the quaternary salt is dissolved by washing the filter cake with 180 ml of hot (SO-TO C) 30 -50% noprolyl alcohol (SO-TO C) and the resulting solution of the even vertical salt of anthrynol is used in the reduction. This solution is poured from a dropping funnel into a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer containing 14 g of iron powder ПЖ4М in 30 ml of 30 ml of water activated by heating for 30 minutes with 1 ml of 98% acetic acid. The mass is boiled for 2 hours. If the temperature is lower, the dichloroethane aeotrope with water and alcohol is distilled to a temperature of 80-83 ° C. After the exposure time, the mass is cooled to 2 ° C, the precipitate containing sludge and 3-methyl aluminum -5-chlorobenzophenone is filtered off and washed with water. The slurry is nicknamed three times 60 ml of hot organic solvent, for example, 6eH3onoNi, black carbon chloride. By; the scientific solution is dried over potash, the solvent is evaporated and 2 0.6-21.6 g of amine ketone containing the main substance are obtained; ga 97.5-98.5%, which is 20.1520, 9 g 100% n6th 2-methylamino-5-orbenzophenone. The yield is 82-85% of the starting anthranil, m.p. 93-95 S. 2-methyl-Mino-5-chlorobenzrfenone in benzene or carbon tetrachloride can be dissolved without any purification. use for chloro acetylation of aminoketone in the production of diazepamy. П РИМ ер 4. Quaternary salt of 5-chloro-3-phenyl anthranil, obtained from 2 3 g of 5-chloro-3-c} enyl anthranil by analogy to example. 3, dissolved in 300-350 ml. hot water {90-95 G) and the resulting solution of a quaternary salt is used in the reduction. The reduction is carried out as described in Example 3. 20.3-20., 8 g of amino ketone are obtained with the content of the main substance 97-97.5%, which is 19.7-20.2 g of 10, 2-methyamio-5-chloroisophenone (80-82% of the original anthranil). ., Example 5. To cooled to a suspension of the Quaternary salt 5-chloro-Zn | a) enyl 1-methyl in tsuchule, obtained from 23 g of 5-chloro-3-phenyl-anthranil as in Example 3, 180 ml of warm (3O-35 G) 30% - isopropyl alcohol and 100 ml of toluene are added. After mixing, the tolus layer is separated, and the aqueous npioMbiBatOT 100 ml of toluene and 100 ml of dichloroethane. After separation of the layers, the obtained quartz-ternary angrylate solution is used for reconstitution. ., -,.:. - -. -. . The reduction is carried out in a similar way to opai-HHpMy in example 3. 2O, 3 2O are obtained, and g of an aminercoma with a basic substance content of 97-97.5%, which is 19, 2 g of 100% 2-methylamino-5-hlrbenzophenone ( SO-82% at baseline anthranyl); Method of obtaining 2-amino- or 2-methylamine-chlorobenzophenone by reduction of y-chloro-3-phenylanthranil or its quaternary salt with dimethyl sulfate with iron in an {solvent solution at the boiling point of the reaction mixture, tl y In order to simplify the process and to increase the yield of the target product, water or aqueous isopropyl alcohol is used as a solvent and the process is carried out in the presence of catalytic amounts of acetic acid.