CS200974B1 - Esters of phosphoryl-and thiophosphoryl-hydrazone of mucochloric acid and method for their producing - Google Patents

Description

The present invention relates to erythrophoryl and thiophophorylhydrazone eateres of mucochloric acid and to a process for their preparation.

Mucohoric acid derivatives of the formula are known from the literature

wherein R ¹ represents alkyl, 2-chloroethyl, R ² represents alkyl, cyclohexyl, 2-phenoxyethyl, 2-chloroethyl / Roczniki Chemii Ann. Soc. Polonorum 46, 39 (1072).

The present invention relates to the novel esters of the pheforyl and thiophoeforylhydrazone of mucochloric acid of the formula I) P-NH-N = CH-C = C-C (I)

I

X ² I21

OR wherein R 1 is alkoxy or phenoxy, R ² is alkoxy or phenoxy,

3 P 3

R and R together with phosphorus form a 5,5-dimethyl-1,3,2-dioxaphosphorinane ring, R is alkyl, X ¹ is oxygen or sulfur, X ² is halogen or alkylthyl, in all cases the alkyl contains 1 to 4 carbon atoms.

An object of the invention is to provide a process for the preparation of compounds of formula I by esterification of phosphoryl, respectively. thiophosphorylhydrazones of mucochloric acid, occurring in the two tautomeric forms of formulas II and III

(II) (III) wherein R ¹ , R ² , X ¹ and X ² are as defined above, with an alcohol of formula

R ³ - OH wherein R ³ is as defined above, in a same alcohol in the presence of sulfuric acid as catalyst in an amount of 2 to 20 b, at the reflux temperature for 1 to 6 hours.

Mucochloric acid phosphoryl or thiophosphorylhydrazone methyl esters of formula I wherein R ³ is methyl may be prepared by reacting diazomethane with a mucochloric acid phosphoryl or thiophosphorylhydrazone of formula II or III in an ether medium at a temperature of 10-30 ° C, or by reacting phosphoryl or thiophosphorylhydrazine

(IV)

1 wherein R, R and X are as defined above with the mucochloric acid methyl ester of formula V

Cl - C - CHO w

Cl - C - COOCH3 in an alcohol medium such as methanol, ethanol or propanol at a temperature of 10 to 60 ° C.

The following examples illustrate in more detail, but do not limit the preparation of the novel mucochloric acid phosphoryl or thiophosphorylhyrazone esters.

Example 1

O-ethyl-O-isobutylthiophosphorylhydrazone methyl ester Mucochloric acid To 10 g of O-ethyl-O-isobutylthiophosphorylhydrazone mucochloric acid dissolved in 100 ml of methanol was added 2.5 ml of sulfuric acid 93% with stirring. The reaction mixture was stirred

200,074 were stirred at boiling for 4 hours. Methanol was distilled off under reduced pressure, to the residue was added 100 ml of toluene, washed with water, 5% sodium carbonate solution and water. Toluene was distilled off under reduced pressure. The residue aa was then purified by column chromatography.

2Q

6.1 g of a colorless liquid were obtained, n _D = 1.5175 and the composition:

Analysis for:

c _u h ₁₉ c ₂ n ₂ ⁰ 4ps

N, 7.42

Found: 7.72 m / m. h. = 377.2 /

8.50% N 8.21% P

8.68% N 8.13% P

18.80% Cl 19.07% Cl

The structure of the compound was confirmed by spectral methods:

CC1 ID,

1 (N-H): 3881 cm

265 cm

M / C = 0 / U / S /

749 cm @ -1 ⁽ cm @ -1 ⁾ : 1621 cm ^{@ -1}

UV spectra in methanol:

λ _ωχ : 220 nm / log:: 660 cm

3.04 / in CC1

4 '= GH-NH ₃ O: 5.40 ppm (S): 6.06 ppm (S): 3.28 ppm (<f)

The following substances were prepared in a similar manner:

Example 2

Ko, ó-Diphenylthiophosphorylhydrazone methyl ether of mucoic acid. t. Mp = 119-120 ° C

Analysis: 10 10 ^ 15 ^ 2 ^ 2 ^ 4 ^

Calculated. N, 6.29

Found: 6.57% N / m. h. = 445.2 /

7.20% S 6.96% P

7.36% 3 6.95% P

15.92% Cl 15.72% Cl

Example 3

5,5-Dimethyl-1,3,2-dioxaphosphorinan-2-thion-2-hydrazone mucoic acid methyl ester

mp = 179-180 ° C Analysis for: ^C 10 ^H 15 ^Cl 2 ^N 2 ^O 4 ^S

Calculate: Find:

7.76% N 7.81 * N / m. h. »361,2 /

8.88% S 8.98% S

8.58 t P 8.79% P

19.63 * Cl 19.58% Cl

Example 4

Q-Ethyl-O-isobutyl-thiophosphoryl-hydrazone ethyl ester of mucoic acid n * ° = 1,5092

Analysis for: ^C 12 ^H 21 ^Cl 2 ^N 2 ° 4 ^K Calculated: 7.16% N

Found: 7.31% N / m. h. = 391,2 /

8.19% S 8.42% S

7.92% P 18.12% Cl

7.82% P 18.42% Cl

Example 5

O-ethyl-O-isobutylthiophosphorylhydresone propyl ester of mucoic acid n £ ° = 1,5085

200 974

Analysis for:

Calculate: Find:

^C 13 ^H 23 ^G1 2 ¹ 2 ° 4 ^IB 6.91% N 7.12% N / mh = 405.3 /

7.91% S 8.05% S

7.64% P 7.58% P

17.50% Cl 17.59% Cl

Example 6

Q-Ethyl-Q-iso-butylthiophosphorylhydrazone mucochloric acid isopropyl ester n ° = 1.5275

Analysis for: C pre hHg ^ C ^ ^NNO ^PS / m. h. »405,3 /

Calcd .: 6.91% N 7.91% S 7.64% P 17.50% Cl

Found: 7.17% N 8.21 SS 8.02 and P 17.79 * Cl

Example 7

Q-Ethyl-Q-isobutylthiophosphorylhydrazone mucochloric acid isobutyl ester

Πρ ° = 1.5060

Analysis for: C ₄ H 2 N ₂ 5 ^{C 1} ₂ O ₄ PS Calc .: 6.68% N

Found: 6.83% N / m. h. = 419.3 /

7.65 and 7.39 and P 16.91% Cl

7.81 and 7.36 and P 16.83 and Cl

Example 8

O, N-Chloro-4-ethylthio-β-Foroyl acrylic acid methyl ester of O, O-diethylthiophosphorylhydrazone

mp = 80-82 ^W C Analysis for: C 18 H 18 ClN 6 O 5 PSg

Calc .: 7.47 and N

Find .:

7.33% H / m. h. a 374,8 /

17.11 and S 8.26% P 9.46 and Cl

17.16 and 3 8.05% P 9.81% Cl

Example 9 Diethylphosphorylhydrazone diethyl ester of mucochloric acid

To 16 g of diethylphosphorylhydrazone mucochloric acid dissolved in 100 ml of ether was added successively at 10 to 20 ° C 100 ml of ethereal diezomethane solution with stirring. The ether was distilled off and the residue was purified by crystallization. 16.8 g of a white crystalline substance with m.p. t. - 78 to 79 ° C.

Analysis for:

Calculate: Find:

IR in CC1 ₄ :

^C 9 ^H 15 ^C1 2 ^N 2 ° 5 ^P 8.41 and N 8.36 and N // W: 3 124 cm " ¹ // P = 0 /: 1 249 cm" ¹

UV v

CH ^ OH max ‘

298 nm / m. h. = 333.1 /

9.30 and P 9.08 and P,

Y / c = 0 /: 1,716 cm / 10 g f: 4.28 /

21.29 and Cl

21.01 and Cl -1

H (C = N): 1639 cm @ 200 974

1 H NMR spectrum in DMSO: -CH- : 8.60 ppm / X / NH : 10.13 ppm / £ / ch ₃ o- : 3.81 ppm / <£ /

Example 10

Mucochloric acid Ο, Ο-diethylthiophosphotylhydrazone methyl ester

To 8 g of methyl mucochloroate in 100 ml of ethanol and added 6.5 g of 0,0-diethyl

-thiophosphorylhydrazine and stirred at 20 ° C for 2 hours. After ethanol was distilled off, the residue was purified by column chromatography. 8.2 g of a white crystalline substance with m.p. t. = 57 to 59 ° C and composition:

Analysis for: C pre HH ^Cl ^N ^O ^PS / m. h. 349,2 /

calc .:

nöjd .:

IR spectra in CCl3s

UV spectra in CH 2 OH:

8.02% N 8.07 * N i // NH /

9.18% S 9.05% S

377 cm '

256 cm

8.87% P 9.025 * P i // C = 0 /: 1744 cm ¹ i // P = S /: 649 cm ¹

20.31 * Cl *

20.11% Cl v / C = N / 1,616 cm ¹ max

219 nm / log £: 3.03 /

Claims (2)

1. Mucochloric acid phosphoryl- and thiophosphorylhydrazone bases of the formula IR ¹ P - NH - N = CH - C = C - C QR ^J Cl Wherein R is alkoxy or phenoxy, R is alkoxy or phenoxy, 12 3 R a R a forms with the phosphorus a 5,5- <3-dimethyl-1,3,2-dioxaphosphorinane ring, R is alkyl, 1 2 X is oxygen or sulfur, X is halogen, alkylthio, in each case alkyl having 1 to 4 carbon atoms. 2. A process for the preparation of a compound according to claim 1, wherein the phosphoryl or thiophosphoryl hydrazone mucochloric acid is present in the two tautomeric forms of formulas II and III. P - NH - N = CH - C = C - C = R ² II II OH _V 1 _in 2 Cl Xl, XH P = N-N = CR-C = C-C OH (II) (III) wherein R ¹ , R ² , X ¹ , X ² are as previously defined, esterifies with an alcohol of formula THE CORNER O 974 wherein R ³ is as previously defined, in the same alcohol in the presence of sulfuric acid as the catalyst in an amount of 2 to 20% at the boiling point of the reaction mixture for 1 to 6 hours, or diazomethane in ether at 10 to 30 ° C . A process for the preparation of the compounds according to claim 1, characterized in that it is impregnated with phosphorous 1 - or thiophosphoryl hydrazine (IV) - in which R ¹ , R ² and X ¹ are as defined above for the mucochloric acid methyl ether of formula V Cl-C-CHO 1 '(A) Cl - C - GOOCH ₃ in an alcohol medium such as methanol, ethanol or propanol at a temperature of 10 to 60 ° C.