CH645087A5 - alpha-Hydroxycarbonyl compounds - Google Patents

Abstract

The compounds of the general formula <IMAGE> in which R denotes methyl or ethyl, R' denotes hydrogen, methyl or ethyl and X represents &rdurule& CH2, &rdurule& CH-CH3 or &rdurule& CHC2H5, are obtainable by eliminating hydrogen cyanide and simultaneously or subsequently removing the radical -COOR'' from a compound of the formula <IMAGE> in which R, R' and X have the above meaning and R'' represents hydrogen or C1-6-alkyl. The compounds of the formula I are known flavourings and/or sugar degradation products.

Description

The invention relates to a new approach to alfa-40 hydroxycarbonyl compounds of the formula

HO .0

45

50

R '' OOC

wherein R, R ', R "and X have the above meaning to form a compound of the formula wherein R is methyl or ethyl and R' is hydrogen, methyl or ethyl and X is> CH2,> CH-CH3 or> CHC2H5.

The process according to the invention is characterized in that a compound of the formula

R''OOC

60

II

R "

II

in which R, R 'and X are as defined above, and R "is hydrogen or C 1-6 alkyl,

3rd

645 087

Hydrogen cyanide and at the same time or subsequently split off the rest -COOR.

The cyanohydrin cleavage can be carried out thermally, acid or base catalyzed.

In the case of thermal implementation, the compound of the formula II is expediently heated to temperatures of approximately 50-400 ° C., in particular approximately 80-250 ° C.

In the case of acid-catalyzed cyanohydrin cleavage, the compound of formula II is suitably mixed with catalytic amounts, e.g. with 1 / 1000-1 / 10 equivalents, or with larger ones, e.g. molar amounts of an acid. It is only essential that the pH of the reaction mixture is below 7.

The nature of the acid is not critical. Inorganic acids, e.g. H2S04, HCl, H3P04, or organic acids, e.g. Formic acid, acetic acid, citric acid, oxalic acid, or acidic ion exchangers, e.g. Amberlite JRC 50 etc. in question.

In the case of base catalytic cyanohydrin cleavage, the compound of formula II is expediently mixed with catalytic amounts, e.g. with 1 / 1000-1 / 10 equivalents, or also with larger ones, e.g. molar amounts of a base. It is only essential that the pH of the reaction mixture is above 7.

The nature of the base is not critical. As bases come e.g. B. in question: inorganic bases such as alkali metal hydroxy

de, e.g. B. NaOH, alkaline earth metal hydroxides, e.g. B. Ca (OH) 2, Mg (OH) 2, alkali metal carbonates, e.g. Na2C03, K2C03, alkali metal bicarbonates such as NaHC03, ammonia, other basic salts such as Na3 P04, K2HP04, borax, basic buffer systems such as NaHC03 / Na2C03, K2HP04 / K3P04 etc., organic bases such as amines, e.g. Triethylamine, pyridine, morpholine etc., salts of organic acids with strong bases, such as sodium acetate, formate, oxalate, citrate, lactate, or basic ion exchangers, e.g. B. Amberlite JRA 400, Dolo wex 1 etc.

The cyanohydrin cleavage can be carried out in the gas phase or in the liquid phase. The presence of a solvent is not necessary, but is advisable.

Preferred reaction temperatures are in particular about 15. 100 ° C in question.

The nature of the solvent is not critical, polar solvents such as water, ammonia, alcohols or apolar solvents such as toluene, benzene, toluene, ether, petroleum ether etc. can be used. Preferred systems are basic ion exchangers in the OH "form / H20, or organic acids or their salts, such as CH3C00H / H20, sodium oxalate / H20, or pyridine / toluene at reaction temperatures of around 100 ° C.

In principle, a product of the formula VI (or VII) is initially obtained after the cyanohydrin cleavage:

R '

II

VI can also be in the enol form VII (X => CH, 5 = C-CH3 or S = C-C2H5).

This COOR "grouping can easily be split off by, for example, first hydrolyzing the ester group COOR" using aqueous acid or base (if R "= alkyl) and the carboxylic acid formed or already present or its salts (R" = H, Alkali metal or alkaline earth metal equivalent) decarboxylated, which, for example can be done by thermal treatment (50-200 ° C).

The cleavage of the COOR "group can, however, also take place under the above-mentioned conditions for the cyanohydrin cleavage, which will be the case in particular if the cyanohydrin cleavage is carried out under drastic conditions. The term" drastic conditions "means in particular:

Acid treatment: pH <3, especially <2

Base treatment: pH <10, especially> 12 The compounds of formula II are new. They also form the subject matter of the present invention as a means for carrying out the method according to the invention.

The compounds of the formula II are advantageous by oxidation of compounds of the formula

VI

Vit wherein R, R ', R "and X have the meaning given above.

40 In particular, alkali metal caate, e.g. KH S05, suitable. "Caroat" R (KHSO5, which contains KHS04 and K2S04) is preferred.

The caroate is expediently used in an amount of 1-2.5 equivalents, in particular 1.1-1.5 equivalents.

The oxidation is preferably carried out in polar solvents, such as water, alcohols, acetone, acetonitrile, or mixtures of such solvents.

The pH of the medium is expediently 50 approximately 3-11, as can be produced in a manner known per se by appropriate buffer systems of the carbonate, phosphate, citrate, borate, NH3 / NH4 + or oxalate type.

The reaction temperature can be, for example, between -10 to 60 ° C, preferably between 0-20 ° C. 55 The compounds of the formula I are generally known; they represent flavors and / or sugar breakdown products.

60

III

example 1

Preparation of 3,5-dimethylcyclopent-2-en-2-olone a) 29.5 g (77.5 mmol) of borax and 24.8 g (0.62 mol) of sodium hydroxide are dissolved in 310 ml of water and cooled ( 17 ° C) with 65 g (310 mmol) of 3-carboethoxy-2-cyano-3,5-dimethylcyclopentanone [III] (made from 65 ethyl methacrylate and sodium cyanide according to H. Stetter et al., Liebigs Annalen d. Chem. (1979), 944-949). 132.2 g (403 mmol) of CaroatR, dissolved in 428 ml of water, are added dropwise at 13 to 19 ° C. within 25 minutes, and it is 3 hours

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the stirred at room temperature. For working up, the reaction mixture is acidified with 30 ml of sulfuric acid (2: 1) and extracted 4 times with ethyl acetate. The organic phase is dried over Na2S04, concentrated and dried under high vacuum for 2 hours. Yield: 69.8 g (100% of theory) of 3-carboethoxy-2-cyano-2-hydroxy-3,5-dimethylcy-clopentanone [II] (mixture of diastereomers); nD20 = 1.4658,

IR: 3400 (OH); 2270 (weak, CN); 1720 (broad, C = 0);

NMR (CDC13): 5 = 4.5-3.9 ppm multiplet / 2 Pr (ester-CH,); 3-1.7 complex multiplet / 4 Pr (3 ring protons + OH); 1.7-1.0 multiplet / 9 Pr (3 x CH3);

MS: 225 (M +), 198.180.

b) 66.3 g (0.03 mol) of the above 3-carboethoxy-2-cyano-2-hydroxy-3,5-dimethylcyclopentanone and 30.2 g (0.4 mol) of sodium acetate (anhydrous) are mixed with 350 ml Water added. The mixture is refluxed for 6 hours. For the purpose of working up, the reaction mixture is adjusted to pH 7 with saturated sodium bicarbonate solution and extracted 4 times with methylene chloride. The organic phases are dried over sodium sulfate, concentrated and dried under high vacuum for 1 hour. (The product can also be crystallized directly from the reaction mixture.) Yield: 42.6 g (73% of theory) of crystalline 2-carboethoxy-2,4-dimethyl-cyclopent-4-en-5-olone [VII], m.p .: 92-93 ° C;

IR (CHCI3): 3540 and 3360 (OH); 1725 (COOC2Hs); 1670 (C = 0);

NMR (CDCI3): S = 6.1 ppm single broad / 1 Pr (OH); 4.14 quartet (J = 7.4 Hz) / 2 Pr (0-CH2-Me); 2.95 doublet x quartet (Jx = 17.6 Hz, J2 = 1 Hz) / 1 Pr and 2.22 doublet x quartet (Jt = 17.6 Hz, J2 = 1 Hz) / 1 Pr (CH2 at C- 3); 2.01 doublet x doublet (J! = J2 = 1 Hz) / 3 Pr (CH3 at C-4) 1.39 singlet / 3 Pr (CH3 at C-2); 1.20 triplet (J = 7.4 Hz) / 3 Pr (CH3 of the ethyl ester);

MS: 198 (M +), 180,153,141,134,124 (100%).

c) 4.8 g (24 mmol) of the 2-carboethoxy-2,4-dimethyl-cyclopent-4-en-5-olone obtained above are mixed with 48 ml of 2N sodium hydroxide solution and stirred for 1 hour at room temperature. For the purpose of working up, the reaction mixture is adjusted to pH 3 with 10% strength sulfuric acid and extracted 3 times with ethyl acetate. The combined organic phases are dried over sodium sulfate, concentrated and dried in a high vacuum for 2 hours.

Yield: 3 g (58.5% of theory) of 2-carboxy-2,4-dimethyl-cyclopent-4-en-5-olone [VII], mp: 98-105 ° C, with elimination of CÓ2.

IR (KBr): 3270 (broad, COOH); 1712 and 1690 (C = 0); 1620 (C = C);

NMR (CD3OD): 8 = 5.9 ppm singlet wide (DOH); 2.92 doublet x quartet (J \ = 17.2 Hz, J2 - 1 Hz) / 1 Pr and 2.25 doublet x quartet (Jj == 17.2 Hz: J2 = 1 Hz) / 1 Pr (CH2 on C-3); 1.97 doublet x doublet (Jx = J2 = 1 Hz) / 3 Pr (CH3 at C-4); 1.30 singlet / 3 Pr (CH3 at C-2); MS: 170 (M +), 152.134, 126.124 (100%), 111.

d) 85.1 g (0.5 mol) of the acid obtained above, ie the 2-carboxy-2,4-dimethyl-cyclopent-4-en-5-olone, are mixed with 851 ml of 10% sulfuric acid and 45 minutes refluxed. For working up, the reaction mixture is brought to pH 7 with 2N sodium hydroxide solution and extracted 3 times with methylene chloride. The combined organic phases are dried over sodium sulfate and dried under high vacuum for 1 hour.

Yield: 57.4 g (91% of theory) of crystalline 3,5-dimethyl-cyclopent-2-en-2-olone [I]. M.p .: 93-94 ° C. The product is identical to the product obtained in Example 4c.

Example 2

The product of Example 1 is obtained in 90% yield if the 2-carboethoxy-2,4-dimethyl-cyelopent-4-en-5-olone [VII] (Example 5b) is treated directly under the above conditions. Mp 93-94 ° C.

Example 3

The product of Example 1d is also obtainable from 3-carbo-ethoxy-2-cyano-3,5-dimethylcyclopentanone [III] if this starting material of Example 5a is treated with CaroatR and the reaction mixture is acidified to pH 1 and refluxed for 24 hours becomes. Working up according to Example 5d gives a yield of 70% pure, crystalline 3,5-dimethyl-cyclopent-2-en-5-olone [I], mp. 92-93 ° C (from water).

Example 4

Production of 3,5-diethylcyclopent-2-en-2-olone a) 3-carboethoxy-2-cyano-3,5-diethylcyclopentanone (III) is described in accordance with H. Stetter et al., Liebigs Annalen d. Chem. (1979 ), 944 obtained in 80% yield if ethyl 2-ethyl acrylate is used instead of ethyl methacrylate, bp 95-116 ° C / 10.05 torr.

IR: 2260 and 2210 (CN), 1755 (C = 0), 1728 (COOAet);

NMR (CDCI3): S = 4.26 ppm quartet / 2 Pr (ester-CH2), 4.0-3.1 different singlets of the diastereomers / 1 Pr (H at C2); 2.8-1.3 multiplet / 7 Pr (3 residual ring protons and 2 ethyl CH2); 1.3 triplet / 3 Pr (ester-CH3); 0.95 triplet / 6 Pr (2 ethyl CH3);

MS: 237 (M +), 208,192,180,163,152,142,135 (100%), 126,106.

This nitrii is oxidized and worked up with caroate analogously to example la and gives 3-carboethoxy-2-cyano-2-hydroxy-3,5-diethyl-cyclopentanone [II] nD20 = 1.4502 in quantitative yield;

IR: 3350 (OH), 2250 (weak, CN), 1730 (broad, ketone

_! _ RsterV

MS: 253 (M +), 237,226,208,181,152 (100%), 141,129, 124,109.

b) The cyanohydrin obtained above is refluxed in aqueous solution according to Example 1b and worked up. 2-Carboethoxy-2,4-diethyl-cyclopent-4-en-5-olone [VII] is obtained in 80% yield;

IR: 3360 (OH), 1725 (COOC2Hs), 1705 (C = 0) 1655 (C = C);

NMR (CDC13): S = 6.0 ppm, singlet, broad / 1 Pr (OH); 4.18 quartet / 2 Pr (ester CH2); 2.95 doublet / 1 Pr and 2.35 doublet / 1 Pr (CH2 at C3); 2.7-1.5 multiplet / 4 Pr (2 x CH2 on ethyl); 1.4-0.7 multiplet / 9 Pr (3 x CH3);

MS: 226 (M +), 197, 181,162,152 (100%), 137,124,109.

c) Treatment of the ester obtained above with sodium hydroxide solution analogously to Example le gives the crystalline 2-carboxy-2,4-diethyl-cyclopent-4-enr5-olone (VIII) in 71% yield;

IR: 3520 (OH), 3200 (broad, COOH), 1705 (broad, C = 0 ketone, ester) 1655 (C = C);

NMR (CDC13): 5 = 7.9 ppm singlet / 2 Pr (OH, COOH); 3.06 doublet / 1 Pr and 2.4 doublet / 1 Pr (CH2 at C-3); 2.8-1.5 multiplet / 4 Pr (2 x CH2 on ethyl); 1.17 triplet / 3 Pr and 0.9 triplet / 3 Pr (2 x CH3);

MS: 169,154,126 (100%), 111,108.

The acid decomposes when heated or standing in 2,5-diethylcyclopent-2-en-2-olone [I], mp. 38.5-39 ° C.

4th

5

10th

IS

20th

25th

30th

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Claims (8)

645 087 2nd PATENT CLAIMS 1. Process for the preparation of compounds of the general formula HO I. where R is methyl or ethyl, R 'is hydrogen, methyl or ethyl and X is> CH2,> CH-CH3 or> CHC2H5, characterized in that from a compound of the formula CN o in which R, R 'and X have the above meaning, oxidized, and from this compound of the formula II hydrogen cyanide and at the same time or subsequently cleaves off the residual COOR ". 3. The method according to claim 2, characterized in that a caroate is used as the oxidizing agent. 4. The method according to claim 1, characterized in that 3-carboethoxy-2-cyano-2-hydroxy-3,5-dimethyl-cyclopentanone is used as the starting material. 5. The method according to claim 1, characterized in that 3-carboethoxy-2-cyano-2-hydroxy-3,5-diethylcy-clopentanone is used as the starting material. 6. Compounds of the general formula i • i is 20th II R " II wherein R, R 'and X are as defined above and R "is hydrogen or C ^ alkyl, Hydrogen cyanide and at the same time or subsequently cleaves the rest -COQR ". 2. Process for the preparation of compounds of the general formula HO, 0 \ wherein X is> CH2,> CH-CH3 or> CHC2H5 25, R is methyl or ethyl and R 'is hydrogen, methyl or ethyl and R "is hydrogen or C 1-6 -alkyl, as an agent for carrying out the process according to claim 1 . 7. 3-carboethoxy-2-cyano-2-hydroxy-3,5-dimethyl-30 cyclopentanone as an agent according to claim 6. 8. 3-carboethoxy-2-cyano-2-hydroxy-3,5-diethyl-cycIo-pentanone as agent according to claim 6. 35 where R is methyl or ethyl, R 'is hydrogen, methyl or ethyl and X is> CH2,> CH-CH3 or> CHC2H5, characterized in that a compound of the general form NC .0