Method of preparing phenylalkylcarboxalic acids

专利摘要:
Phenylalkylcarboxylic acids of the formula (I) are prepared by oxidising alkene derivatives of the formula (II). The substituents R<1> to R<8> are defined in Claim 1. Examples of oxidising agents which can be used are potassium permanganate or chromium trioxide in acid medium or ozone-saturated oxygen. Ozonides formed as intermediates are decomposed with hydrogen peroxide. Phenylcarboxylic acids of the formula (I) can be used as pharmaceuticals by reason of their excellent anti-inflammatory properties. <IMAGE>
公开号:SU895282A3
申请号:SU772545902
申请日:1977-11-22
公开日:1981-12-30
发明作者:Себени Рудольф；Корбонитш Деже；Палоши Эндре；Генци Чаба；Хейя Гергели；Молнар Эржебет；Кишш Пал；Кинзел Ида
申请人:Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра Рт (Инопредприятие)；
IPC主号:

专利说明:

(54) METHOD FOR OBTAINING PHENYLALKYLKARBONE
ACID
one
The invention relates to organic synthesis, specifically to a method for producing fenipaps and carboxylic acids, which exhibit anti-inflammatory properties and are used as baking agents.
The closest in technical essence and achievable results to the proposed is a method of obtaining pheny of carboxylic acids, for example | Q
2- (3-phenoxyphenyl) -propionic acid, which consists in the interaction of yu-oxyacetophenone with bromobenzene in the presence of potassium carbonate, followed by treating the resulting 3-phenoxy acetophenone with anhydrous methanol in the presence of NaBH, after which the resulting ot-methyl-3-phenoxybenzyl the alcohol is treated with PBBH in CCA and then with NaCN, with isospezuyu-20 hydrolysis of the obtained 2- (3-phenoxyphenyl) -propionitripa in an alkaline medium TI.
The yield of the target product but exceeds 80% .2
The disadvantage of this method is the multi-stage process, while the resulting intermediate products require complex cleaning, in addition, the yield of the target product is not high enough.
The purpose of the invention is to simplify the process and increase the yield of the target product.
The goal is achieved by the fact that in the method of obtaining phenylalkylcarboxylic acids of the general formula
R - CH - SAT
where R is hydrogen or lower alkyl;
R is hydrogen, fluorine;

权利要求:
Claims (2)
[1]
I is an alkyl or phenoxy ipn phenyl or phenylamino group substituted by 12 halogen atoms, or R and 1 together with phenylshi form a naphtyp substituted by CH O - group, consisting of that. that the anken derivative of the general formula R-CH-CH C Ff is as defined above, wherein R and R are; hydrogen, lower up or phenyl j Bw / A JJJWJ-4 (mrikJAiABAx -j I - lower alkyl or phenyl or R and P together form 1,5-pentylene, is subjected to oxidation from -80 to using CMiOd or ClTjO in an aqueous acetic medium acid or oxygen containing 6-8% 0 in methylene chloride, followed by decomposition of the resulting ozonide with hydrogen peroxide. The yield of the desired product is 88-94% by weight. The alkane derivatives, which serve as an organic substance, are obtained by the Wittig reaction as a result of the dehydration of the corresponding tertiary alcohol I Example 1. 188.23 g (0.5 mol of 1,1-diphenyl L-3 - (3-4oxyphenyl) -but was dissolved in 200 ml of methylene chloride. The solution was cooled to -78 ° C and then for Ozonized oxygen is passed through it for 12 hours, after which the solvent is removed, the residue is dissolved in 100 ml of acetic acid. The resulting solution is poured dropwise into a mixture of 114 g of 30% hydrogen peroxide, 5 ml of sulfuric acid and 200 ml of water. During this operation, strong cooling due to heating is necessary. The solution is boiled for two hours, then cooled and extracted with 3X 5OO ml of ether. The ether phases are washed with sodium hydroxide solution. The aqueous phase is acidified and extracted with 3x 500 ml of chloroform. After drying, the extract is evaporated, the residue is distilled. 109.01 g of 1- (3-phenoxyphenyl) propionic acid are obtained. Yield 9 O wt.%, 57, boiling point 190-192 C / O, 4 mm Hg. Example 2. The method described in example 1, from 126.17 g (0.5 mol of 1,1-dimethyl l-3- (3-phenoxyphenyl l) -butene-1, gives 2- (3-phenoxyphenyl) -propionic acid with a yield of 88 wt.%. Example 3. The method described in example 1, from 146.2 g {0.5 mol 8 24 2- (3-phenoxyphenip) -1-cyclohexylidenepropane, 1- (3-phenoxyphenyl) 1ropionic acid with a yield of 88 wt.%. Example 4, the method described in example 1, from 150,69 g (0.5 mol) of 1-phenyl l-3- (3-phenoxyphenyl l) -butene-1 get 2- (3-phenoxyphenyl) -propionic acid with a yield of 93% by weight. Example 5. 46,98 g (0.125 mop) 1,1-diphenyl l-3- (3-phenoxyphenyl l) -butene 1 solution A solution of 27 g of chromium trioxide in 30 ml of water is added dropwise to this solution in 5OO ml of acetic acid. After heating for 1 hour, the acetic acid is removed and the residue is treated with 5OO ml of sulfuric acid. The acidic solution is prepared in Example 1. 25 g of 2- (3-phenoxyphenyl) propionic acid (82.5 wt.%) are obtained which boils at 19 ° -190 ° C / 4, 4 mm Hg. Example 6. By the method described in Example 5, from 31.54 g (0.125 mol) of 1,1-dimethyl-3- (3-phenoxyphenip) -butene-1, 2- (3-phenoxyphenip) -propionic acid is obtained. Yield 81 wt.%, Example 7. The method described in Example 5, from 36.65 g (0.125 mol) of 2- (3-phenoxyphenyl) -1-cyclohexylideneifonana, gives 2- (3-phenoxyphenip) -propionic acid. Output 84 wt.%. Example 8. The method described in example 5, from 37.67 g (0.125 mol) of 1-pheny p-3 - (3-phenoxyphenyl l) -bene-1-get 2- (5-phenoxyphenyl) -propionic acid. Output 84 wt.%. Example 9. To a mixture consisting of 3.76 g (0.01 mol) 1,1-diphenyl-3- (3-phenoxyphenyl) -butene-1, 1OO g of ice water and 420 g of acetic acid are added with stirring 4.74 g (O, OZ mol) manganese iron, potassium. The dosage rate is chosen so that the temperature does not exceed 3 ° C. The mixture is filtered, alkalinized, filtered again, and then dried strongly. After acidification, the treatment is carried out in the manner described in Example 1. 2.23 g (92.5% by weight) of 2- (3-phenoxyphenyl l) -propionic acid is obtained, which boils at 190-192 C / O, 4 mm Hg .st. Example 10. The method described in example 9, from 2.52 g (0.01 mol) ll-b -dimethyl-3- (3-phenoxyphenyl l) -butene-1 get 2- (3-phenoxyphenyl) -propionic acid . Yield 90 wt.%. Example 1 By the method described in Example 9, 2- (3-phenoxyphenip) D-propionic acid is obtained from 2.92 g (0.01 mol) of 2- (3-h}) enoxyphenip) -1-1xc-hexylidenepropane. Output 94.5 wt.% Example
[2]
2. By the method described in Example 9, from 3.01 g (0.01 mogsh) of 1-phenyl-3- (3-phenoxyphenyl) -butene-1, 2- (3-k}) enoxiphenip) propionic acid is obtained. The yield is 94.5 wt.%, Example 13. 47, 30 D of 1,1-diphenyl-3- (2-fluoro-4-biphenipyl) -butene-1, DL is dissolved in 500 ml of acetic acid. At solution, 27 g of chromium trioxide in 30 ml of water is accumulated at 7NCO. The mixture is heated for 1 hour, then acetic acid is removed and the residue is acidified. The acidic solution is extracted with chloroform. The extract is dried and evaporated. 24.06 g of 1- (2-flu-1 -4-biphenylyl) -pulpionic acid is obtained, which melts at 110-111 ° C. Yield 78.5 wt.%. Example 14. To a mixture consisting of 3.64 g (0.01 mol) of 1,1-diphenyl-3- (6-methoxy-2-naphthyl) -butene-1, 100 g of ice water and 40 O ml of acetic acid acids are added while stirring with O- 4.74 g (0.03 mol) of potassium permanganate. The mixture was pinched, basified again (} 1% and then condensed forcibly. After acidification, the mixture was extracted with chloroform. The extract was dried and then evaporated. 2.1 g of 2- (6-methoxy-2-naphthyl) -propionic acid was obtained ( 91.2% by weight), which melts at 153-155 ° C. The product can be recrystallized from a mixture of acetone and hexane. Example 15. To a mixture consisting of 3.4 g (0.01 mol) 1,1-diphenyl- H- (4-isobutylphenyl) -butene-1, SOO g of ice-water and 4OO ml of acetic acid are added with stirring at 4.74 g (0.03 mol, manganese acid drip. The reaction mixture is The procedure described in Example 1 is obtained. 1.86 g of 2- (4-isobutylphenyl) propanoic acid (9O, 6% by weight) is obtained, which melts at 75-76 ° C and can be recrystallized from petroleum ether. Example 16 To a mixture of 4.72 g of 1,1-diphenyl-3-G2- (2,6-dichlorh}) enyl l) amino-pheny lpropen-1, iOO ml of boiled water and 400 ml of acetic acid are added by 4, by mixing at 0-3: 4.74 g of manganic acid, go.The reaction mixture is separated by the method described in Example 14. 2.53 g of 2- (2,6-diphenphenyl) -aminophenylacetic acid is obtained (78.5 wt.%), which melts at 156-158 C. Example 17. Received There are 2- (6 - methoxy-2-naphthyl). - propionic acid. 182 g (0.5 mol) of 1., 1-diphenyl-3- (6-methoxy-naphyl (butene-1 is dissolved in 200 ml of methylene chloride. The mixture is cooled with solid carbon dioxide to -78 ° C and passed through A stream of oxygen containing 6–8% O with a rate of 20 l / h for 12 hours is then removed. The solvent is removed and the residue is dissolved in 10 ml of acetic acid. The solution is added to a mixture of 114 g of 30% SO, 5 ml of 2 MP of water. The mixture is boiled for 2 hours, after cooling, it is extracted with chloroform. After drying and evaporation of the solution, a product melting at 153-155 ° C is obtained, which crystallizes from a mixture of tones with hexane. Example 18. 45.5 g (0.125 mol) of 1,1-diphenyl-3- (6-methoxy-2-naphthyl) - -butene-1 are dissolved in 35 O ml of acetic acid and added at 7 ° C a drop of an aqueous solution of 27 g of C h-OO. After further heating, acetic acid is removed by distillation and the residue is acidified. After extraction with chloroform, the product is isolated and purified as indicated in the previous example. Example 19. Obtain 2- (4- isobutylphenyl) propionic acid. 170 g (0.5 mol) of 1,1-diphenyl-3- (4-isobutylphenyl) -butene-1 is dissolved in 250 ml of methylene chloride. Mixture oh- It is harvested with the help of solid carbonic acid up to -78 ° C and through it, a current of oxygen containing 6–8% 0 is pumped at a rate of 2O l / h for 12 hours. After removal of the solvent, the residue is dissolved in acetic acid. The solution is added to a mixture of 114 g (30%). 5 ml Nl 50d and 200 ml of water. The mixture is boiled for 2 hours, then the acidic aqueous solution is extracted with chloroform. After drying the solution and evaporation, a product melting at 75-7 ° C is obtained which can be crystallized from petroleum ether. Example 20.21.25 g (0.125 Mpb) 1,11-diphenip-3- (4-isobutylphenyl) -butene-1 is dissolved in acetic acid and an aqueous solution of 27 g ChjOj is added dropwise at 7 ° C. The mixture is heated for another hour, then acetic acid is distilled off and the residue is extracted by acidification of chlorine chloride)). After the usual processing methods, melting is obtained with 75-76 C 2- (4-isobutyl-phenyl-propnonic acid) Example 21. 2- (2,6-dichlorophenip) aminophenylacetic acid is obtained. 4.72 g 1,1-diphenyl -3 -2- (2,6-dichlorophenyl) -amino3-phenylpropane-1 is dissolved in 30 ml of methylene chloride and the oxygen flow is passed through this solution containing 6-8% Oj at a rate of 2O l / h while cooling to -78 ° C with the help of solid carbon dioxide, Ozonide decomposes according to the preceding signs and then further processed further according to the previous examples. Example 22. 4.72 g 1.1 - diphenyl-3 / -2- (2.6 -dichlorophenyl) -amino J-phenylpropen-1, as indicated in Example 20, is acidified with 2.7 g of CGDO, and the product melting at 156-157 ° C is obtained. 2 .- (2-flu-4-biphenylyl) -propionic acid is obtained. 3.7 g of 1,1-diphenyl- (2-fluoro-4-biphenyl) -butene-1 solution) are mixed, containing 1OO ml of water and 420 ml of acetic acid and 4.74 g of CMiOd are added so that the temperature does not exceed 3 ° C. Filtered, alkalinized, filtered again and then evaporated. The residue is acidified and extracted with chloroform. It is processed in the usual manner and a product is obtained melting at llO-lll C. Example 24. 185 g of 1,1-diphenyl-3 - (2-fluoro-4-bipheny lyl) -butene-1 is dissolved in 200 ml of methylene chloride. The solution is cooled with carbonic acid to -78 ° C, an oxygen stream containing 6–8% 0 is passed through it at a rate of 20 l / h for 12 hours. The resulting OZONID is decomposed as described in the previous examples and, after extraction with chloroform, is treated with ordinary silica and clear). This gives a product melting at 110-11 ° C. The invention The method of obtaining phenylalkylcarboxylic acids of the general formula | K - CH - COOH de hydrogen or lower alkyl; R -. hydrogen, fluorine; I - C, Cjt alkyl or phenoxy or enyl or phenylamino group substituted by -2 halogen atoms or R in combination with phenyl form naphthyl substituted by SNO group, in order to simplify the process and increase the yield of the target product, the alkene derivative is common Formula I L -CH-Cn with R D2 where R, R, have the abovementioned, R - hydrogen, lower alkyl, or phenyl; R is lower alkyl or phenyl or lower alkyl or phenyl or R and Ix 5 together form 1,5-pentylene; is subjected to oxidation from -80 to + 70 ° C using KMK) 4 or in an aqueous acetic acid medium or with oxygen containing 6-8% 0 in methylene chloride, followed by decomposition of the ozonide formed with hydrogen peroxide. Sources of information taken into account in the examination 1. US Patent No. 36О0437, cl. 260-52О, publ. 1971 (prototype).

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引用文献:

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JP6104831B2|2014-03-05|2017-03-29|東レ・ファインケミカル株式会社|Method for producing benzoic acids|

法律状态:

优先权:

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HUCI001695|HU180811B|1976-11-23|1976-11-23|Process for preparing phenyl-alkyl-carboxylic acids|

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