CS229087B1 - 2-/omega - alkoxycarbonylalkyl/-gamma-butyrolactone and method of preparing same - Google Patents

Description

The present invention provides 2- (omega-alkoxycarbonylalkyl) gamma-butyrolactone and a process for its preparation.

The compounds of the present invention are among the hydroxydicarboxylic acid derivatives, generally termed the ester lactones. These acid and butyrolactone derivatives have not been described in the literature. Among similar substances prepared under similar reaction conditions, some 2-alkyl-gamma-butyrolactones and 2- (10-carboxydecyl) gamma-butyrolactone (Nikishin G.I .: USSR AO 144 478 (1962)) are reported in the patent literature. Further disclosed are 2- (3-carboxypropyl) - and 2- (4-carboxybutyl) gamma-butyrolactone, which have been prepared by alkaline hydrolysis and decarboxylation of the alkylation products of 2-carbethoxy-gamma-butyrolactone with 4-chlorobutyrate or 5-chlorovaleran methyl (Morisawa K. et al. Jap. Pat. 18117 ('64) (1962);

Chem. Abstr. 62, 5,197 (1965)).

SUMMARY OF THE INVENTION The present invention provides a process for the preparation of 2- (omega-alkoxycarbonyl) gamma-butyrolactone

O _from CH ₂ CH ₂ C _n H _2n COOR

wherein n is 1 to 9 and R is alkyl of 1 acid of formula II (I) to 4 carbons consisting of unsaturated ester

CH 2 = CHC _n H ₂ COOR (II) wherein n is 1 to 9 and R is alkyl β 1 to 4 carbons act by gamma-butyrolactone in a 5- to 9-fold molar excess, in the presence of a catalyst, e.g. 20-fold excess of butyrolactone in the presence of metal oxide or a mixture thereof, e.g. butylperoxide and copper oxide. The reaction is carried out at a temperature of 50 to 75 ° C for 5 to 8 hours. The resulting lactonester I addition product is then isolated and purified by fractional distillation under reduced pressure or, for the high-boiling product, by silica gel chromatography.

The present process for the preparation of the lactonesters of the general formula 1 makes it possible in a simple way to prepare a number of homologues of said substances. Isolation of the products is simple: excess butyrolactone is removed by fractional distillation of the reaction mixture and product I is obtained in sufficient purity by distillation under reduced pressure. In the case of higher boiling unsaturated esters, the crude adduct is purified by silica gel column chromatography. The method allows the preparation of substances I on a larger scale. An advantage of the process of the present invention is less butyrolactone and target consumption. butylperoxide, or its complete replacement with inexpensive copper (II) oxide catalyst, while maintaining relatively good yields.

After introduction of the double bond to the butyrolactone ring, compounds I can be used as starting materials for the preparation of 10-oxaanalogs of prostaglandin E ₁ , which has already been described in the literature (Hauser F. Μ., Huffmann, C. C. Tetrahedron Lett. 1974. 905). . In addition, the compounds I are starting materials for the preparation of the corresponding hydroxydicarboxylic acids. The preferred production method is described in more detail in the following examples.

Example 1

A mixture of 25.8 g (0.3 mol) butyrolactone, 19.2 g (0.15 mol) methyl 5-hexenoate and 4.4 g (0.03 mol) ditero. of butylperoxide was dropped to 77.5 g (0.9 mol) of butyrolactone at 155-165 ° C with stirring for 6 hours. The mixture was then heated at the same temperature for 2 hours, the excess butyrolactone was distilled off, along with the decomposition products of the catalyst, through an alcohol column under reduced pressure and the residue rectified. 17 g (53%) of 2- (5-methoxycarbonylpentyl) -gamma-butyrolactone, boiling at 134-135 ° C / 1 mmHg, were obtained. For C ^ HH ^ gO ^ (mol weight 214.3) calculated: 61.66% C, 8.47% H;

Found: C, 61.57; H, 8.28. Infrared (Chloroform): 1375, 1440, 1735.

770 cm ^-1 .

Example 2

A solution of 14.22 g (0.1 mol) of ethyl 5-hexenate and 2.2 g (0.015 mol) of di-tert-butylperoxide in 17.2 g (0.2 mol) of butyrolactone was added dropwise at 150-160 ° C with stirring during 6 hours to 43 g (0.5 mol) of butyrolactone. After. For an additional 2 hours of heating, 10.3 g (45%) of 2- (5-ethoxycarbonylpentyl) - gamma-butyrolactone b.p.

137-138 ° C / 53 Pa. For C ₁₂ H ₂₀ C ₄ (mol. Weight 228.3) calculated 63.14% C, 8.83% H found 63.30% C, 9.13 & H. Infrared spectrum: 1370, 1440.1 720, 1765 cm ^- .

Example 3

A mixture of 25.8 g (0.3 mol) butyrolactone and 12.8 g (0.1 mol) methyl 5-hexenate was added dropwise to 43 g (0.5 mol) butyrolactone in suspension with 2.3 g with stirring for 6 hours. (0.03 mol) of copper oxide. After cooling, the mixture was filtered, excess butyrolactone was distilled off under reduced pressure through a puncture column, and the residue was distilled using an oil pump. 10.2 g (47%) of 2- (5-methoxycarbonylpentyl) - gamma-butyrolactone were boiled at 122-125 ° C / 40 Pa. Pro (mol. 214.3) calculated C 61.66%, 8.47 H;

found: 61.38% C, 8.70% H. The infrared spectrum was identical to that of the product described in Example 1.

l ·

Example 4

A mixture of 18.9 g (0.22 mol) butyrolactone, 11.4 g (0.08 mol) methyl 6-heptenate and 2.24 g (0.016 mol) diterc. of butyl peroxide was added dropwise to 43 g (0.5 mol) of butyrolactone with stirring at 150-160 ° C for 5 hours. After 2 additional hours of heating at the same temperature, 8.2 g (45%) of 2- (6-methoxycarbonyl-hexyl) -gamyl-butyrolactone, boiling at 129-131 ° C / 27 Pa, was isolated in the same manner as in Example 1. For C ₁₂ H ₂ O 2 (mol. Weight 228.3) calculated: 63.14% C, 8.83% H; found: 63.9% C, 8.98% H. Infrared (chloroform): 1370, 1430, 1725, 1765 cm @ -1.

•

Example 5 (To 51.6 g (0.6 mol) butyrolactone heated to 155 ° C was added dropwise with stirring

25.8 g (0.3 mol) butyrolactone, 19.8 g (0.1 mol) methyl 10-undecenate and 2.1 g 0.015 mol) di-tert-butylperoxide over 6 hours. After further heating for 2 hours, the product was isolated as described in Example 1 above. 16.2 g (57%) of 2- (10-methoxycarbonyldeeyl) - gamma-butyrolactone, which boiled at 155 ° C / 7 Pa and crystallized upon cooling, was isolated, mp 42 ° C. For C 15 ^H 28 ° 4? ^mo · ^{1 2} ·· Weight 284.4) calculated: 67.58% C, 9.92% H; found: 67.60 ° C, 9.97 ° C. Infrared spectrum: 1380, 1440, 1735, 1775 cm ^-1 .

Example 6

A solution of 12 g (0.05 mol) of butyl 10-undecenate and 1.4 g (0.01 mol) of di-tert-butylperoxide in 30.1 g (0.35 mol) of butyrolactone was added dropwise to the suspension 4 over 6 hours with stirring. 6 g (0.06 mol) of cupric oxide in 86 g (1 mol) of butyrolactone at 160-165 ° C. The reaction mixture was then further heated at the indicated temperature for 2 hours and then filtered after cooling. After excess butyrolactone was distilled off, the crude product (11 g) was chromatographed on 200 g of silica gel Ch (100-160 µm). Eluting with chloroform, afforded, after drying for 8 hours at 40 C. ^At 67 mbar and 9.4 (65%) of 2- (10-butoxykarbonyldecyl) -gamma-butyrolactone. For C ^H H. ^O ^ (mol weight 326.5) calculated: 69.90% C, 10.50% H H found: 69.53% G,

10.83% H. Infrared (chloroform): 1370, 1430, 1740, 1775 cm @ -1.

Claims (4)

SUBJECT OF THE INVENTION 2- (omega-alkoxycarbonylalkyl) gamma-butyrolactone of the general formula I o CH ₂ CH ₂ C _n H _2n COOR (I) wherein n is 1 to B 13 is alkyl of 1 to 4 carbons. 2. A process for the preparation of 2- (omega-alkoxycarbonylalkyl) -gam-but-ylactone of the formula I, characterized in that the unsaturated acid ester of the formula II CH ₂ = CHC _n H ₂ COOR (II) wherein n is 1 to 13 and R is C 1 -C 4 alkyl reacts with gamma-butyrolactone in a 5- to 9-fold molar excess in the presence of a catalyst, e.g. an organic peroxide, or 5- up to a 20-fold excess of butyrolactone in the presence of metal oxide or a mixture thereof, e.g. tert-butyl peroxide and cuprous oxide, at a temperature of 150 to 175 ° C for 5 to 8 hours. 3. A process according to claim 2, wherein the catalyst is used in a molar ratio of 1 to 2: 10 to the starting ester II. 4. A process according to claim 2 wherein the resulting lactonester of formula (I) is isolated and purified by fractional distillation under reduced pressure or by chromatography on silica gel.