SU564811A3 - Method for obtaining derivatives of 3-(2,5-dihydro-5-oxo-3-furfuryl)-urea or their salts - Google Patents

Description

(54) METHOD FOR OBTAINING DERIVATIVES OF 3- (2,5-DIHYDRO-5-OXO-3-FURYL) URIDE OR THEIR SALTS

The process is usually carried out at 60-80 ° C in the presence of an acid catalyst, for example p-toluenesulfonic acid, and using equimolar amounts of the starting materials.

As the ester of 4-haloalkanoyl acetic acid, ethyl 4-bromoacetoadetate can be used.

The reaction is carried out in a solvent, for example in toluene, or preferably in benzene.

Refluxing is continued until water is stopped in the Dean-Stark trap. The product precipitating during the reaction is filtered off and chromatographed and / or crystallized.

.Example. 1- tert - Butyl - 3 - (2,5-dihydro - 5 - oxo - 3 - furyl) - urea.

A mixture of 4.65 g (0.04 mol) of tert-butylurea and 4.0 g (0.04 mol) of 2,4-furandione (tetronic acid) in 60 ml of benzene is heated under reflux and a Dean-Stark nozzle, the formation of a transparent solution and then isolation of a heavy solid. After cessation of the water, the reaction mass is cooled to room temperature, the precipitate is filtered off, washed with ether or benzene, dried, and 6.7 g of solid are obtained, so pl. 175-177 ° C (decomp.). After recrystallization from water: ethanol (60:40). T.PL. 197-198 ° C.

Calculated,%: C 54.53; H 7.12; N 14.13.

Found,%: C 54.30; 53.99; H7.63; 7.43; N 14.09, 14.00.

PRI mme R 2. 1 - tert - Butyl - 3 - (2,5-dihydro - 5 - oxo - 3 - furyl) - urea.

A mixture of 20.9 g (0.1 mol) of ethyl - 4 - bromoacetoacetate and 11.6 g (0.1 mol) of tert - butylurea in 200 ml of benzene is heated under reflux until clenched in water, cooled to room temperature, the precipitate is filtered off washed with ether or benzene, dried and 6.9 g (35%) of crystals are obtained, so pl. 189-192 ° C. By double or triple recrystallization from Water-alcohol mixture (60:40), 3.9 g (20%) of the title compound are obtained, m.p. 196-197 ° C, non-depressing melting point.

Example 3. 1-tert - Butyl - 3- (2,5 - dihydro - 5 - oxo - 3 - furyl) - urea.

A mixture of 8.4 g (0.04 mol) of ethyl - 4 - bromoacetate, and 4.6 g (0.04 mol) of tert - butyl urea in 100 ml of benzene is heated to 68 ± 1 ° C for 150 min, cooled to room teMnepaTypbi the precipitate is filtered off, washed with benzene, substantial, triturated with a dilute solution of potassium bicarbonate and washed with water. Then the solid is triturated with 50 ml of 10% sodium hydroxide, the precipitate is filtered off, the filtrate is acidified to 6N. hydrochloric acid to pH 1, the precipitate is separated by washing with water, and 1.2 g (15%) of crystals are obtained, m.p. 195-196 ° C (decomp.). After recrystallization from water-ethanol (60:40), yield 0.7 g (9%), so pl. 199-200 ° C (decomp.).

The IR spectra of the products obtained in Examples 1-3 are ideal.

Example4.1-tert-Amil-3- (2.5-dihydro-5-oxo-3-furyl) urea.

4 g of tert-amyl urea are added to a solution of 3 g of 2,4-furandi in 100 ml of benzene, heated under nitrogen at 3 hours under reflux for ordinary water removal, cooled, concentrated, recrystallized from acetonitrile and 2.5 g of the target substances, so pl. 169-171 ° C, the structure of which is confirmed by the data of IR and NMR spectroscopy.

Example 5. 1- (1- Methylclopengyl) - 3 - (2,5 - dihydro - 5 - hydroxy - 3 - furyl) - urea.

 Example 4, from 3 g of 2,4-furandione and 4 g of 1-methylcyclopentyl urea, 3 g of the desired product are obtained, mp. 170 ° C (decomp.)

PRI me R 6. 1 - (1 - Methylcyclohexyl) - 3 (2.5 - dihydro - 5 - oxo - 3 - furyl) - urea. Starting from 5 g of 2,4-furandi and 6g of 1-methylcyclohexyl urea, the same as Example 4, the target compound is synthesized, mp. 183 ° C (decomp.).

PREMIER 7.1 - (1,1 - Dimethylpropargil) - 3 - (2.5 digilro - 5 - oxo - 3 - furyl) - urea.

To a solution of 5 g of 2,4 - furandi in 100 ml of benzene, b g of 1,1 - dimethylpropargylurea is added, heated under reflux for 3 hours | Under nitrogen with water removal, cool, concentrate, dissolve the residue in 25 ml of ethyl acetate and filter . The filtrate is chromatographed on 150 g of silicic acid, eluting with a mixture of benzene-ethyl acetate-methanol (60:30:10 in percent), the resulting crystalline substance recrystallized tacg from adetonitrile and 2.5 g of the title compound are isolated, mp. 178 ° C (decomp.)

Example 8.1- (1,1-Dimethylbutyl) - 3 (2, dihydro - 5 - oxo-3 - furyl) - urea.

14 4 g of 1,1 - dimethylbutylurea and 100 mg of p-toluenesulfonic acid are added to a solution of 22 g of methyl 4-bromoacetoacetate in 200 ml of benzene, heated under reflux for 4 hours under nitrogen to remove water, cooled, concentrated, the residue is chromatographed pa 400 g of silicic acid, eluting with a mixture of benzene - ethyl acetate - methanol (60:30:10 in percent), the resulting crystalline substance is recrystallized from ethyl acetate and obtain 1.8 g of the target substance, so pl. 130-132 ° C.

Analogously to example 7 using a compound of the formula

BUT

 0 0

"LlT-rllLT About

(NzSN2

and the corresponding urea derivative (preferably in the presence of traces of p-toluenesulfonic urea derivative

And CHj o

I. JII

CH, C — C — N — C — NH—, g 1 1 iCH H

SNS about

III

СН | СН-СН2-0-Ш-С- «Н2

sn.

Sis about

I ii

d-ms-dng

1I

nn he

CH5 about

but

NH-

about

SNZ ns-: mn2 n

 about

- / t ns-: mn.2

JV ,, o

x

 II

 kn-tn n.

h / s ". about

acids) obtain the desired compounds by decree (the ones in Table J, Table 2 or Table 3 corresponding).

Table 1

Target mix

Mr. CH about

I I II

CH2 C-C N-0-N -7

II1

- CHjH n

t.ll. 167 ° C (decomp.)

nn about

I I and

 - with - N - With - 7 I I I Ch., 0

n (jHj Hj n

nooh oh

I ii

CH с- N - с - N I 1I 0

ShgN n 0

SNS

1LL (razut.)

N -7 I C 0 H 0K -7

I Z7) 0 n 0СНз

 -CI, II

n o

sn

xh-so i (H-7

0

table 2

Urea derivative

SNS about

I ii

С-КН-С-Ш, I

SNH

Table 3.

Target compound

SNH about

I ii

CHj-C-m-O-l HSI, Cllx- iH.2

PRI me R 9. 1 tert - Bugsh 3 - (2,5-dihydro-5 - ok co - 2 n - propyl - 3 - furyl) urea.

A mixture of 7.1 g of 5 - n - propyl - 2.4 - furandione, 6.0 g of tert-butyl urea and 0.2 g of p.toluenesulfonic acid is heated for 8 hours with a reflux condenser in benzene, cooled, the benzene is evaporated, the residue is triturated with diluted with caustic soda and ether, filter tert-butyl urea, dry the ethereal solution, evaporate, chromatograph the residue on silicic acid, eluting with toluene-ethyl acetate (60:40), and obtain the desired product.

Similarly, starting from 5 - n-butyl - 2,4-furandione, 1 - tert - butyl - 3 - (2 - n-butyl - 2.5 - dihydro - 5 - oxo - 3 - furyl) urea is obtained. m.p. 125-126 ° С (preliminary sintering).

Example 0. 1-tert-Butyl - (2,5 - dihydro 4 - methyl - 3 - furyl) - urea.

30.4 g of 3-methylfurandione in 200 ml of benzene is heated for 16 hours under reflux, oh-. bent, benzene visharivak, triturate the syutatok with a dilute solution of potassium bicarbonate, filter out the solid, triturate it with 50 ml of 10% ed, filtered, acidified nl filtrate 6 n. hydrochloric acid before, cooled and the crystals of the target product are separated, m.p. 253-254 ° C (decomp.).

Example 11. Sodium salt 1 - tert - butyl - (2,5 - digishchyu - 5 - oxo - 3 - furyl) urea.

To a solution of 0.8) sodium hydroxide in 150 ml of methanol was added 4.0 g of 1 tert-butyl - 3 - (2.5 dihydro - 5 - oxo - 3 - furyl) - urea, and the mixture was stirred to form one the mixtures are scorched and a vitreous residue of the sodium salt is obtained. The NH acid maximum in the NMR spectrum of 1 - gret - boogil 3 - (;, 5 - dngilro - 5 oxo3 - furyl) - urea was found at 9.2 ppm in the sodium salt it is absent.

The structure of the compounds obtained in examples 9-11 was confirmed by the data of IR and NMR spectroscopy and elementary analysis.

Claims (3)

1. The method according to the emission of derivatives of 3- (2,5-dihydro-5-oxo-3-furyl) urea of the general formula R4 ei o (Y R2 J-H-C3-H-C 4, 1  / X-o to where RI, Rj and RZ -Ci-C4 is alkyl; C2-C4 alkenyl, C2-C4 - alkynyl, provided that RI, Hz and RZ together contain no more than six atoms carbon and that only one of Rj, Rj and Rd-alkyl, and two others can form together dacloalkyl or cycloalkenyl; X-methylene, unsubstituted or substituted with methyl, ethyl, propyl or butyl; R4 is hydrogen or methyl, provided that if P4 is methyl, then. X-methylene, or sodium, potassium or calcium salts of a compound of formula (I), where X-methylene is unsubstituted or substituted by methyl or ethyl, so that molene derivatives are general formulas RI. ABOUT I II B2 - s-1 n: - (- mi2 60 where PI, B, and B, imeck) biiiiiicvKh) pin) nach 11 nor, is subjected to interaction with the compound of the General formula AT 4 BEFORE where R4 and X are as indicated above, or with ester of 4-hapoidal alkanoyl acetic acid in an organic solvent, such as benzene, when heated, and isolate the desired product in free form or as the sodium, potassium or calcium salt of the compounds of formula (I), where X is methylene, indispensable or mixed with methyl ihsh ethyl. 12 2. Method POP.1, characterized in that the process is carried out in the presence of an acid catalyst, for example p-toluenesulfonic acid. 3. A method according to claim 1, characterized in that the heating is carried out at 60-80 ° C. Priority featured: 04/17/74 with RI, R2 and Yaz -Ci-C4 alkyl, C2-C4 alkenyl, C2-C4-alkynyl, provided that RI, Rj and RS together contain no more than six carbon atoms, that only one of R ,, RJ or Rj - quinil, and 0 two others can form cycloalkynyl or cycloalkenyl; X-methylene, unsubstituted or substituted with methyl or ethyl; R4 is hydrogen, and the preparation of alkali metal salts of the compounds of the FrmulnP compounds .11.03.75 with X-methylene, mixed with propyl or butyl; R4-methyl, provided that X is methylene.