SU950714A1 - Process for producing esters of acetoacetic or malonic acid - Google Patents

Description

The invention relates to an improved process for the preparation of acetoacetic, cyanoacetic or malonic acid esters of the general formula

ABOUT

RR-CH-C

OCjHg (1)

where R is COiCiHs,, CN;

R-C4.Hg, CH2.CH-CHi, q Hs-CH, which can be used as starting compounds in organic synthesis.

A known method of producing esters of formula 1) by alkylating with halohydrogen acetoacetic and malonic esters at temperatures up to using acetals as a solvent in the presence of caustic alkali at a molar ratio of the starting ether, halohydrocarbon and alkali equal to 2: 1.5: 1-2.5 Cl .

The disadvantages of this: 1 method are low yields of alkylation products (43-61% for acetoacetic and up to 34% in the case of malonic) and the use of inaccessible solvents.

The purpose of the invention is to increase the yield of the target products.

This goal is achieved in that according to the method for producing acetoacetic or cyanoacetic 5 or malonic acid esters by halogenation of a compound of the formula

(Ii)

where R is as defined above, in 4-methylenetetrahydropyran (MTHP) in the presence of caustic alkali with a molar ratio of a compound of formula (II), a halohydrocarbon and caustic alkali, equal to 1: 1-1.5: 1-1.5, with

- 60-85 ° С.

Example. Allylacetoacetate

“A) In a four-tube flask equipped with a reflux condenser, mechanical stirrer, addition funnel and thermometer, 2.8 g (0.05 mol) of KOH, 50 ml of MTPH (previously dried over KOH and re-gmanny; t.kip. (760 mmHg c) and heated to 80-85 ° C with stirring until a suspension is formed.

Then, at a temperature of about 10-15 minutes, with an addition of 6.5 g (0.05 mol)

30 acetoacetic ester. The reaction mixture is cooled to bb-bz C and 6.05 g (0.05 mol of allyl bromide is added dropwise for 3035 minutes), then heated at bs-cc for 2-3 hours. Then the reaction mixture is poured onto ice, MTHP is extracted and dried over MgSO.sub.After removal of the solvent by distillation in vacuo, 7.7 g (90.59%) of ally acetoacetic ester are obtained, bp 9397C / 10 mm Hg, 1.4365 lt.t. 6) Out of 2.0 g (0.05 mol) of NaOH,. 6.5 g (0.05 mol) of acetoacetic ester and 6.05 g (0.05 mol) of methyl bromide; allyl in 50 ml of MTHP after heating for 2-3 hours at 60-65 ° C, 7.8 g are obtained (91, 76%) allylacetoacetic ester with BP. 92-97 C / 10 mmHg, 1.4368 p. PRI mme R 2. Benzyl ether acetic acid. a) Analogously to Example 1 of 2.8 g (0.05 mol) KOH, 6.5 g (0.05 mol) of acetoacetic ester and 6.35 g (0.05 mol) of benzyl chloride in 70 ml of MTPD after 3- 4 h of heating at 80s gives 9.5 g (86.36%) of benzylacetoacetic ester, b.p. 122-125s / 2.5 mmHg Pr1,4965. Lie .: t.kip. 156 mm Hg b) Analogously to example 1 of 2.0 g (0.05 mol) of NaOH, 6.5 g (0.05 mol) of acetoacetic ester and 6.35 g (0.05 mol) of benzyl chloride in 70 ml of MTHP after 3- 4 hours of heating, 9.3 g (84.55%) of benzyl acetoacetic ester are obtained, b.p. 12q-123/2 mmHg, 1.4962. PRI me R 3. n-Butylacetoacetic ester. a) Analogously to example 1 of 2.8 g (0.05 mol) KOH, 6.5 g (0.05 mol) of acetoacetic ester and b, 85 g (0.05 mol) of n-butyl bromide in 50 ml of MTHP after 5 -6 hours of heating at 80 gives 6.2 g (66.67%) of n-butylacetic ethyl acetate, b.p. 108-113 with / / 13.5 mm Hg, p |, ° 1.4330. Lit .: tkip. 112-115 C / 15 mm Hg b) Analogously to example 1 of 2.0 g (0.05 mol) of NaOH, 6.5 g (0.05 mol) of acetoacetic ester and 6.85 g (0.05 mol) of n-butyl bromide in 50 ml of MTHP after 5 -6 h of heating at 80 get 6.4 g (68.82% n-butylacetoacetate ether with a boiling point / 10 mm Hg and n 1.4325. Example 4., C-Dimethyl-acetyl acetoxy ether. A) Analogously to an example 1 of 2.8 g (0.05 mol) KOH, 6.5 g p, 05 mol) of acetoacetic ester and 5.23 g (0.05 mol) of TTt T-dimethylallyl chloride a in 50 lMTHP after 3-4 hours heating at 80 ° C gives 8.5 g (85.87%) of Tf, G of dimethyl ethyl acetoacetic ester with a boiling point. 124-126 s / 14 mmHg, n | ° 1.4478. Lit .: tkip. 120-122s / 1112mm pTicT. b) Analogously to Example 1 out of 2.0. g (0.05 mol) NaOH, 6.5 g (0.05 mol) of acetoacetic ester and 5.23 g (0.05 mol) of U, -jr-dimethylallyl chloride in .50 ml of MTHP after 3-4 hours of heating with 80 ° C, 8.4 g (84.85%) are obtained; E 7D11 methyl ethyl acetoacetic ester with a boiling point of. 122-125 C / 14 mmHg ,, .4476. , Example 5. Allylmalonate ether. a) Analogously to example 1 of 2.8 g (0.05 mol) of KOH, 8.0 g (0.05 mol) of malonic ester and 6.05 g (0.05 mol) of allyl bromide in 70 ml of MTHP after 6- 7 hours, heating at 65-70s gives 8.2 g (82%) of the allyl ester with mp. 108-112 C / 11 mmHg, “PD 1,4355. Lit .: tkip. 222-223 C. b) Similarly to example 1 of 2.0 g (0.05 mol) of NaOH, 8.0 g (0.05 mol) of malonic ether and 6.05 g (0.05 mol) of allyl bromide in 70 ml of MTHP after 6-7 hours of heating at 65-70 ° C, 8.1 g (81%) of allyl malonic ester are obtained, b.p. 107-113 C / 11 mmHg, p 1.4350. Example 6. Benzylmalonate ether. a) Analogously to Example 1 of 2.8 g (0.05 mol) KOH, 8.0 g (0.05 mol) of malonic ester and b, 35 g (0.05 mol) of benzyl chloride after 7-8 hours of heating with 80-85 ° C, 8.6 g (68.8%) of benzyl malonic ester are obtained with a bp. 128-132 C / 2 mmHg n 1, 4910. Lit .: t. Kip. mmHg. b) As in Example 1, from 2.0 g (0.05 mol) of NaOH, 8.0 g (0.05 mol) of malonic ester and 6.35 g (0.05 mol) of benzyl chloride after 7-8 hours of heating at 80 ° -85 ° C give 8.5 g (68%) of benzyl malonic ester with mp. 128-131 C / 2 mmHg, n-g 1.4910. Example 7. Allyl cyanoacetic ester. a) Analogously to example 1 of 2.8 g (0.05 mol) of KOH, 5.65 g (0.05 mol) of ethyl cyanoacetic acid ester and 6.05 g (0.05 mol) of allyl bromide in 70 ml of MTPH after 4-S h of heating at 65-70 ° C give 7.0 g (91.5%) of allyl cyanoacetic ester with mp. 108-112 ° C / 10 mmHg, nl 1-, 4380. Lit .: tkip. 223p. b) Analogously to example 1 of 2.0 g (0.05 mol) of NaOH, 5.65 g (0.05 mol) of ethyl cyanoacetic acid and 6.05 g (0.05 mol) of allyl bromide. in MTPH after 4 -5 hours of heating at 65-70 seconds, 6.9 (90.19%) allyl cyanoacetic ester is obtained, b.p. 109112 C / 10 mm Hg, n |, ° 1.4373. PRI me R 8. Allylacetoacetate ether. a) In a four-tube flask, equipped with a reflux condenser, mechanical stirrer, dropping funnel and thermometer, 4.2 g (0.075 mol) of KOH, 50 MP of MTGP (pre-dried over KOH and distilled; t kip. 104s / 760 mm Hg and heated to 80-85 ° C under stirring to form a suspension, then 9.75 g (0.075 mol) of acetoacetic ester are added dropwise at a temperature of about 80 ° C for 10-15 minutes.The reaction mixture is cooled to 6065 ° C and 30-35 minutes, 6.05 g (0.05 mol) of allyl bromide are added dropwise, then they are heated at b5-70 ° C for 2-3 hours. Then the reaction mixture is poured onto , extracted with MTHP and dried over MgSO4. After removal of the solvent and distillation in vacuo, B (2) (96.47%) of allyl acetoacetic ester (bp 93-97 C / 10 mm Hg, p = 1.3365) is obtained. : bp 196-206 ° C b) Of 3.0 g (0.075 mol) of NaOH, 9.75 g (0.075 mol) of acetoacetic ester and 6.05 g (0.05 mol) of allyl bromide in 50 ml of MTPH after 2-3 hours of heating at 60-65 ° C, 8.1 g (95.29%) of allyl acetoacetic ester are obtained, b.p. 92-97 / 10 mm Hg, p1 1.4368. PRI me R 9. Benzylacetoacetate. a) Analogously to Example 8, from 4, 2 g (0.075 mol) KOH, 9.75 g (0.075 mol) of acetoacetic ester and 6.35 g (0.05 mol) of benzyl chloride in 70 ml of MTHP after 3-4 hours heating at 10.2 g (92.73%) of benzylacetoacetic ester with mp. 122-125 ° C / 2.5 mmHg, Pr1.4965. Lit .: tkip. 156-162s / / GZ mm Hg b) As in Example 1, out of 3.0 g (0.075 mol) of NaOH, 9.75 g (0.075 mol of acetoacetic ester and 6.35 g (0.05 mol) of benzyl chloride at 10 ° C, 10.1 g are obtained (91.82 %) benzyl acetoacetic ester with a bp 120123c / 2, 5 mm Hg, p 1.4965. Example 10 n-Butylacetoacetic ester a) Analogously to Example 8 of 4.2 g ( 0.075 mol) KOH, 9.75 g (0.075 mol of acetoacetic ester and 8.65 g (0.05 mol) of n-butyl bromide in 50 ml of MTHP, after 5-6 hours of heating at 80 ° C, 6.8 g are obtained (72, 47%) n-butyl acetoacetic ester with a bp 108113 C / 13, 5 mm Hg, 1.4330 Lit .: a bp 112-115C / 15 mm Hg b) Similarly Example 1 of 3 g (0.075 mol) NaOH, 9.75 g (0.075 mol acetone oxy ester and 6.85 g (0.05 mol) of n-butyl bromide in 50 ml of MTHP after 5-6 hours of heating at 80 ° C, 6.7 g (72.04%) of n-butylacetone ethyl acetate with b.p. 100-104С / / 14 mm Hg, p-p 1.4325. Example ir. F iTf-Dimethyl-acetylacetic ester. A) Analogously to example 8 of 4.2 g (0.075 mol) KOH, 9.75 g ( 0.075 mol) of acetoacetic ester and 5.23 g (0.05 mol) of y, f-dimethylallyl chloride in 50 ml of MTHP after 3-4 hours of heating; 9.2 g (94.9%) of f are obtained, y-dimethyl-acetyl acetoacetate with bp 120-122 C / 11-12 mm Hg. Lit .: so kip. 120-122C / 11-12 mmHg b) Analogously to example 1 of 3.0 g (0.075 mol) of NaOH, 9.75 g (0.075 mol) of acetoacetic ester and 5.23 g (0.05 mol) of Y - y-dimethylallyl chloride in 50 ml of MTPD after 3-4 Heating at 80 ° C. gives 9.1 g (92.68%) of y, α-dimethyl ethyl acetoacetate, b.p. 122-125 C / i4 mm Hg, 1.4476. Example 12. Allylmalonate ether. a) Analogously to Example 8 of 4.2 g (0.075 mol) KOH; 12.0 g (0.075 mol) of malonic ester and 6.05 g (0.05 mol) of allyl bromide in 70 ml of MTHP after heating for 6-7 hours at 65-70 ° C, 8.4 g (87%) of allyl methyl ether are obtained with bp 108-il2C / ll mmHg, p 1.4355. Lit .: tkip. 222-223 p. b) Analogously to example 8 of 3.0 g (0.075 mol) of NaOH, 12, O g (O, 075 mol) of malonic ester and 6.05 g (0.05 mol) of allyl bromide in 70 ml of MTHP after 6-7 h heating at 65-70s gives 8.5 g (85%) of allyl malonic ester with mp. 107-113 ° C / 11 mmHg,, 4350 .. Example 13. Benzylmalonate ester. a) Analogously to Example 8 of 4.2 g (0.075 mol) KOH, 12.0 g (O, 075 mol) of malonic ester and 6.35 g (0.05 mol) of benzyl chloride in 70 ml of MTPD after 7-8 h heating at 80-85s gives 9.3 g (74.4%) of benzyl malonic ester with mp. 128-132 s / 2 mmHg 1.4910. Lit .: tkip. 169 C / / And mm Hg b) Analogously to example 1 of 3.0 g (0.075 mol) of NaOH, 12.0 g (0.075 mol) of Möshonovoy ether and 6.35 g (0.05 mol) of benzyl chloride in 70 ml of MTHP after 7-8 hours of heating with 80-85 ° C, 9.2 g (73.6%) of the benzyl-malonic ester are obtained with boiling point 128-131 sec / 2 mm Hg, St., tij 1.4910. Example 14. Allyl cyanoacetic ester. a) Analogously to example 8 of 4.2 g 0.075 mol) KOH, 8.48 g (0.075 mol) of ethyl cyanoacetic acid ester and 6.05 g (0.05 mol) of allyl bromide in 70 ml of MTHP after 4-5 h heating at 65-70 ° C, 7.3 g are obtained (95.43% 1 allyl cyanoacetic ester

, 7 $ 507148

with T, KHn.f08-112c / 10MMpT.CT.-, n | f; where R -, CH CO, CN

1.4380. Lit .: tkip. . about g and ru-pn g g n g

6} Analogously to Example 1 of 3.0 g C, C11, CH,

(0.075 mol) NaOR, 8.48 g (0.075 mol) of alkylation of the cyanoacetic acid-halogenohydroethyl ester of the cyanic acid- "" compound of the formula and 6.05 g (0.05 mol) of ally bromide- 5 .. R CH, CCU C (Well P) la in 70 MP MTPH after 4-5 hours of heating - the above values, 7.2 grat solvent are obtained in the presence of caustic

(94.12% of allyl-dianuksusnogo ester SSC, chi, about tl and h a y u and i with

bp YU-PZ S / Yu mmHg, HJ,. That, in order to increase output

 target product, as a solution. The authors use the 4-methylenetetrahydride formula of the invention ropyran and the process is carried out at a molar

a method for preparing acetoxus-C ° esters; ;; d ° -GaTe oPelo and,

Noah or cyanacetic or malonic, equal 1: 1-1,5: 1-1,5, at 60-85 0

Acids General Formula Sources of Information

Taken in the examination of RR-CH-C (1) 1. UK Patent No. 582191,

 OCaHf3947 (prototype).

Claims (1)

Claim A method of producing esters of acetoacetic or cyanoacetic or malonic acid of the general formula t θ RR-CH - C (1) ⁴ 0С _g Н ₅ where R - C0 _a C ₂ H _ff , CH СО, CN R * - СДН ^ СН ^ СН ^ СН ^ С ^ -СН ^, by alkylation with a halocarbon-hydrogen compound of the formula. . R CH ^ CQj, C ^ H y (L) where R has the above meanings, in a solvent in the presence of caustic alkali, characterized in that, in order to increase the yield of the target product, 4-methylenetetrahydropyran is used as a bolt solution and the process is carried out at molar ratio of compound of formula (II), a halohydrocarbon and a caustic alkali being 1: 1-1.5: 1-1.5, at 60-85 ⁱⁿ C.