SU1209688A1 - Method of producing derivatives of 2-iminothiazolidine - Google Patents

Description

one

The invention relates to methods for producing 2-aminothiazolidine derivatives, which are used as intermediates in the synthesis of biologically active compounds, as well as biopids.

The purpose of the invention is to increase the yield and expand the range of target products, reduce the duration and simplify the process,

Example 1, Preparation of 2- (allimino) thiazolidine.

To a solution of 4.0 g of 5-hydro-, 9-diox-4,6-diaza-5-phosphaspiro 4, 4 nanoan in 50 ml of benzene is added dropwise under stirring at a temperature of 75-80 ° C. 2.63 g of allyl isothiopinate. The reaction mass is heated for 1 hour at the same temperature, benzene is removed, the residue is stirred with 50 ml of water, alkalinized with sodium hydroxide or potassium solution to redox, the extract is extracted with ether, the extract is dried over magnesium sulfate, the ether is removed and the residue is distilled yut. 2.88 g (76.0%) of 2- (allylimino) thiazolidine are obtained. T.kim, 98- (0.5 mm Hg, Art.), Mp, 40-4l c

Found,%: C 50.62; And 7.15; N 19.68; S 22.38;

calculated,%: C 50.70; H 7.04; N 19.72; S 22,53,

PMR spectrum (solution in, Bruker).

Allyl: (8 NCH-t 3.91; SF 5.20; SHg 5.05; SHc 5.93 m, d ;; J 6.8; J NCH ,, HCH2-H;, 9; L HdH 17, 2; J HgH 10.3; JH (Hg 1.9 Hz; Triplets of protons of the cycle: SNCH23.99; SSCHi 3.28 m, d, J NH 6.9 Hz,

P p and m e p 2, Preparation of 2- (phenylimino) thiazolidine,

To a solution of 3.77 g of 5-hydro-1,9-diox-4,6-diaza-5-phosphaspiro 4,4 j nonane in 50 ml of benzene with stirring at a temperature of 70-80 ° C, added sweat dropwise m 3, 4 g of phenyl isothiocyanate, the reaction mass is heated for more than 1 hour at 80-85 ° C, benzene is removed, the residue is stirred with 100 ml of water, alkalinized with sodium hydroxide or potassium solution until alkaline, the precipitated crystals are separated, dried and the solid is recrystallized from a mixture of water and acetone. 3.27 g (73.0%) of 2- (phenylimino) thiazolidine are obtained. Mp 16f 163 C.

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Found,%: C 60.80; H 5.68; N 15.75; S 18.36, C, H ,,,

Calculated,%: C 60.67; H 5.62; 5 N, 15.73; S 18.00,

PMR spectrum (solution in CB COCDj), Protons 8 6.93-7.44 ppm, (multiplet), Protons of the cycle: triples PNCH2.3.95; S SI, 3.3 ppm, J MN O 7.3 Hz,

PRI me R 3 Getting 2- (allylimino) -3-methylthiazolidine,

To a solution of 5.28 g of 4,6-dimethyl-5-hydro-1,9-diox-4,6-diaza-5-phosphorus-15 faspiro 4,4 nonane in 15 ml of benzene with stirring and at a temperature of 20 ° С was added a solution of 2.92 g of allyl isothiocyanate in 5-10 ml of benzene is dripped, the mixture is heated for 0.5 h at 70-80 ° C, 20 the solvent is removed, the residue is heated for 5-10 min at 110-120 ° C and distilled . 3.17 g (68.5%) of 2- (allylimino) -3-methylthiazolidine are obtained. T, kip. 78-80 ° C (0.5 mm Hg, st,), 25 p 1.5375.

Found,%: C 53.64; H 7.59; N 17.83; S 20.60, C, 1, N, S.

Calculated,%: C 53.85; H 7.69; 30 N17.95; S 20,5,

of those (alumina, HT of a st. activity) mobile Laza - ether; the only spot is p 0.80; mobile Laza - ether-hexane (1: 1); the only 35 is Pj 0.41,

PMR spectrum (solution in,), Allyl: st mSRg 3.73; 5 PP5.1; P-g 4.95; SP. 5.91 m, d,; J 5.4;

J Ex2-Nj J NCHj-Hv 1.9; J NdN

40 17.2; J NcNr 10.3; J, 9 Hz, Cycle Protons: Triplets S NCP 3.42; S SCH 3.18 m, d J HH 6.6 Hz. Group M SP,: singlet S 2,82 ppm,

PRI me R 4. Obtaining 2- (phenyl45-imino) -3-methylthiazolidine.

To a solution of 5.12 g of 4,6-dimethyl-5-hydro-1,9-diox-4,6-diaza-5-phosphasi-pyro 4,4 nonane in 15 ml of benzene with stirring and at a temperature of 20

50 is added dropwise 3.88 g of phenyl isothiocyanate in 10 ml of benzene. The mixture is heated for an hour at 75-80 ° C, benzene is distilled off, and then held for 10-15 minutes in a vacuum of 0.5-1.0 mm Hg.

53 at 120-130 ° C in a bath, cooled, extracted with ether or acetone, the solvent is removed and the residue is recrystallized from the mixture into ode-acetone,

4.90 g (89.0%) of 2- (phenylimino) -3-methylthiazolidine are obtained. M.p. 88-90 ° C. .

Found,%: C 62.35; H 6.26; N 14.33; S 16.63. C, oH, 2N, S

Calculated,%: C 62.50; H 6.25; N 14.56; S 16.66.

those (alumina, grade II): mobile phase - ether: the only spot is RI 0.85; the mobile phase is ether-hexane (1: 1): the only trace is R 0.63.

SR spectrum (solution in CD, COCD,). Protons multiplet S 6.85 - 7.22 ppm Groton cycle: triplet NCHj 3.59; S SCH 3.19 m, d J NH 6.5 Hz. Group YSK: singlet 2.97 MD.

EXAMPLE 5 Preparation of 2- (Phenyl-imino) -3-methylthiazolidine.

To a solution of 1 1.75 g (0, ib6 mol) of 5-hydro-1,9-diox-4,6-diaza-5-phosphaspiro 4,4 nonane in 30 ml of benzene with stirring and at a temperature of 20 ° C. drop a solution of 8.1 g (0.06 mol) of lenisol thiocyanate in 20 ml of benzene. The treatment of the reaction mass and the isolation of the target vein are carried out in the same way as. as described in Example 4. 10.2 g of (817) 2- (phenylimino) -3-methylthiazolidine are obtained.

PRI me R 6. Preparation of 2- (allimino) thiazolidine.

Out of 12.0 g (0.08 mol) of 5-hydro-1,9-diox-4,6-diaza-5-fosLaspiro 4,4j nonane and 8.7 g (0.088 mol) of allyl isothiocyanate in the same way as described in Example 1, 8.4 g (74%) of 2-allylimino thiazolidine is obtained.

Take p7. To a solution of 4.5 g of 5-hydro-1,9-diox-4,6-diaza-5-phosphaspiro 4,4j nonane 60 ml of benzene is added dropwise with stirring at a temperature of 60-65 ° C, 0 allylisothiocyanate. The reaction mixture was kept at the same temperature for 1 h, benzene was removed, the residue was stirred with 60 ml of water, alkalized with potassium hydroxide solution until alkaline, the separated oil was extracted with ether, the extract was dried over magnesium sulfate, the ether was removed, the residue was distilled. 1.15 g (27%) of 2- (allylimino) thiazolidine are obtained.

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PRI me R 8. Preparation of 2- (phenyl-imino) thiazolidine.

To 3.6 g 4,6-dimethyl-5-hydro-1,9-diox-4,6-diaza-5-phosphaspiro 4,4

5 nonane in 10 ml of benzene under stirring and a temperature of 2 ° C were added 2.7 g of phenyl isothiocyanate in 10 ml of benzene, the mixture was heated for 1 hour at 75- 80 ° C, the benzene was removed, and then 10 minutes were kept. vacuum, 0.5-1 torr at a bath temperature of 140-150 ° C, cooled, extract-cosiness ether, the solvent is removed, the dark red residue is treated with activated charcoal in alcohol, the alcohol is removed, the residue is recrystallized three times from a mixture of water -acetone. 1.32 g (34%) of 2- (phenylimino) thiazolidine are obtained.

20 Example9. Preparation of 2- (allylimino) -3-methylthiazolidine.

To a solution of 4.6 g (0.026 mol) of 4,6-dimethyl-5-hydro-I, 9-dibks-4,6-diaza-5-phosphaspiro 4,4. nonana in

25 15 ml of benzene with stirring and a temperature of 20 ° C. Is added dropwise a solution of 1.8 g (0.018 mol) of allyl isothiocyanate (the ratio of allyl isothiocyanate to spiran

30 0.69: 1) in 5 ml of benzene. The treatment of the reaction mixture and the isolation of the desired product are then carried out as described in Example 3. 1.44 g (36% based on spi (allylimino) -3-methylthiazole) are obtained.

Dina.

PRI me R 10. Getting 2- (phenylimino) thiazolidine.

To a solution of 3.74 g (0.025 mol) of 5-hydro-1,9-dioxa-4, b-diaza-5-phosphapiro-4,4 nonane in 50 ml of benzene is added with stirring and a temperature of 70-80 ° C. drop m 4.08 g

(0.030 mol) of phenyl isothiocyanate (the co-ratio of isothiocyanate-spira is 1.2: 1). The treatment of the reaction mass and isolation of the target product is carried out as in Example 2,

2.6 g (48.3% based on isothiocyanate) of the substance are obtained. In contrast to example 2, in the obtained substance, when studying by TLC, in addition to the spot with RJ 0.41, corresponding to 2- (phenylimino) thiazolidine, there is a spot with RI 0.63 (alumina, GG activity, mobile phase ether - hexane 1: 1).

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Example P. Preparation of 2- (fe-1h with US-BO, raise temperanylimino) -3-methylthiazolidine, tour up to 120-30 ° C, withstand

To a solution of 6.3 g A, 6-dimethyl-5-10 min, P-xylene is distilled off in vacuhydro-1, 9-dioxa-A, 6-diaza-) phosphasome 0.5-1 mm Hg. Art. Further processing

Pyro 4.4 nonane in 20 ml of P-xylene residue and the separation of the product by drying while stirring and 20 ° C are added as described in Example 4,

4.8 g of phenyl isothiocyanate dropwise 5.9 g (87%) of 2- (phenylimino) in 10 ml of 1-xylene are obtained, the mixture is heated to-3-methylthiazolidine "

Claims (2)

METHOD FOR PRODUCING PRODUCTION- NEW 2-IMINOTIAZOLIDINE of the general formula 1 --- O · ™ ,. where P, is an atom of hydrogen or lower alkyl; P ₂ is lower alkylene or phenyl by reaction of an isothiocyanate of the general formula II Mcs, where R ₂ has the indicated meanings, with a phosphorus-containing ethanolamine derivative when heated in a solvent medium, characterized in that, in order to increase the yield and expand the range of target products, reduce the duration and simplify the process, the isothiocyanate of formula 11 is reacted with a compound of general formula 111 G ° W °] VD1 _g where R has the indicated value as a phosphorus-containing derivative of ethanolamine. With a molar ratio of reagents (0.9-1: 1): 1, respectively, at a temperature of 70-130 C in an inert organic solvent.