synthesis of some substituted 1,3-thiazolines and 1,3-thiazolidines

SYNTHESIS OF SOME SUBSTITUTED 1,3-THIAZOLINES AND

1,3-THIAZOLIDINES

A. N. Pudovik, V. K. Khairullin, M. A. Vasyanina, I. K. Pokrovskaya, O. N. Kataeva, I. A. Litvinov, and V. A. Naumov UDC 542.91:547.789.1

Sodium salts of 2,2-dimethyl-4-mercapto-5-oxo-l,3-thiazoiine and 2~xo-3-mercapto- l-thia-4-azaspiro[4.5Jdec-3-ene, obtained from a solvate of sodium cyanodithioformate with three molecules of dimethylformamide, acetone, or cyclohexanone in the presence of morpholine, react with chlorothioformic dimethylamide with the formation of 2,2-dimethyl-5-oxo-4-(dimethylaminothiocarbonylthio)-l,3-thiazoline and 2- oxo-3-(dimethylaminothiocarbonylthio)-l-thia-4-azaspiro[4.5]dec-3-ene, respectively, and during acidolysis by hydrochloric acid they are converted to 2,2-dimethyl-5- oxo-4-thiono-l,3-thiazolidine and 2-oxo-3-thiono-l-thia-4-azaspiro[4.5]decane. The latter compounds are facilelyphosphorylated by dialkyl chlorophosphonates at the nitrogen atom. The reaction of the solvate of sodium cyanodithioformate with three molecules of dimethylformamide with chloroacetone in the presence of morpholine occurs anomalously with the formation of cyanothioformic morpholide.

We studied the reaction of sodium salts of 2,2-dimethyl-4-mercapto-5-oxo-l,3-thiazoline and 2-oxo-3-mercapto-l-thia-4-azaspiro[4.5]dec-3-ene [i, 2] with chlorothioformic dimethylamide. The reactions occur during heating with abstraction of sodium chloride and the formation of 2,2-dimethyl-5-oxo-4-(dimethylaminothiocarbonylthio)-l,3-thiazoline (I) and 2-oxo- 3-(dimethylaminothiocarbonylthio)l-thia-4-azaspiro[4.5]dec-3-ene (II). An analogous reaction of these sodium salts with dialkyl chlorophosphates occurs complexly, and it is not possible to recover the pure products from the reaction mixture.

By treatment with hydrochloric acid, sodium salts of 2,2-dimethyl-4-mercapto-5-oxo-l,3- thiazoline and 2-oxo-3-mercapto-l-thia-4-azaspiro[4.5]dec-3-ene were converted to 2,2-dimethyl-5-oxo-5-thiono-l,3-thiazolidine (III) and 2-oxo-3-thiono-l-thia-4-azaspiro[4.5]decane (IV). Compounds (III) and (IV) are facilely phosphorylated at the nitrogen atom by dialkyl chlorophosphates. Thus, during the reaction of compound (III) with diethyl chlorophosphate, 2,2-dimethyl-5-oxo-4-thiono-3-(diethoxyphosphoryl)-l,3-thiazolidine (V) is formed, and the reaction of compound (IV) with dibutyl chlorophosphate gives 2-oxo-3-thiono-4-(dibutoxyphosphoryl)-l-thia-4-azaspiro[4.5]decane (VI)

N . C--SNa s

11 t l (CH~)~N--CCI_NaCI \ c (L=o // \% /

[ ~ItCI --NaCl

ltN C=S ? !1\', I ( ICO)~PCI, (C,II~)sN

--(C:II~)~N-|ICI C C=O

/ \ / II S

(111), (iv)

s II

N- C--S--C--N(Clts)2

\C =O / \ /

I~ S (l), (11)

P(O)(Ow)~.

N C=S

(2 C=O 1~ s

(v), (Vl)

]I CII:~(I), ( l I l ) ; I{ -~ l{~ - - (Cf I : )~ - - ( l l ) , (IV); l l :=CtI3 , R ' = C 2 H ~ ( V ) ; |{ -}- I{=- - (CI i2)~- - , IV=C41tg(VI) .

A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Branch, Academy of Sciences of the USSR. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. ii, pp~ 2590-2593, November, 1990. Original article submitted June 22, 1989.

0568-5230/90/3911-2345512.50 @ 1991 Plenum Publishing Corporation 2345

Fig. i. Geometry of cyanothioformic morpholide molecule in crystal. Hydrogen atoms are not shown.

The reaction of chloroacetone with the solvate of sodium cyanodithioformate with three molecules of dimethylformamide in the presence of morpholine under the conditions indicated in [2] occurs anomalously with the formation of cyanothioformic morpholide, which was charac- terized by PMR and IR spectra and by x-ray diffraction analysis. Morpholine hydrochloride was also recovered from the reaction mixture. The formation of these products can be explained by the scheme

S ~) o ~, ::

N- -C- -C- -SNa .3 I lC- -N(CI Ia ) ~ -~- CICIIaCCII a S () ()

N- -C- -C- -CI + [NaSCtI=CCtla] "t- 311C--N(C113). S S i ,

0 . 5 N = c C c I + HN o - - ~ 0 . ~ N - - C - - C - - N " "; o + 0 . ; ~ . c l . ~ - - ~ / k . _ . /

( V I 1 )

o X__/

Carrying out the reaction in the presence of 2 moles of morpholine did not significantly increase the yield of compound (VII). In the crystal, the moelcule of (VII) was in a particular position on plane m, and only methylene groups of the morpholine ring that were ordered in two symmetric positions with respect to this plane came out from it. The conformation of the morpholine ring was twist. The C6NIC 2 plane constituted an angle of 20 ~ with the plane of sp2-hybridized carbon. We should note that according to data of gas electron diffraction the unsubstituted morpholine has a chair conformation [3] (Fig. i).

EXPERIMENTAL

The IR spectra were obtained on a UR-20 spectrometer in the range 400-3600 cm -~. The PMR spectra were recorded on a Varian T-60 instrument (60 MHz), the internal standard was TMS, and the solvent was acetone-d 6. The chemical shifts of the 31p nuclei ~ were measured on a KGU instrument at 10.2 MHz, and the standard was 85% H3PO ~.

X-Ray Diffraction Analysis. The crystals of compound (VII) are orthorhombic, and at 20~ a = 11.355(4), b = 9.322(2), c = 7.271(2) ~, Z = 4 and dcalc = 1.34 g/cm 3. The space group is Peam, and the molecule is in a particular position on plane m. The cell parameters and the intensities of 366 independent reflections with F 2 i 3o were measured on an Enraf- Nonius CAD-4 automated K diffractometer (l MoK~, graphite monochromator, w/(s/30), and 0 < 30~ The structure was interpreted by a direct method according to the MULTAN program, ~nd nonhydrogen atoms were recalculated in an anisotropic approximation. All H atoms were de- tected from difference series, and their contribution to structural amplitudes was taken into account in the final recalculation stages. The final values of the divergence factors R = 0.045 and R W = 0.061. All calculations were carried out on a PDP 11/23 computer according to SDP programs. The coordinates of nonhydrogen atoms of (VII) are given in Table i.

2,2-Dimethyl-5-oxo-4-(dimethylaminothiocarbonylthio)-l,3-thiazoline (I). To 3.5 g of 2,2-dimethyl-5-oxo-4-mercapto-l,3-thiazoline sodium salt in 60 ml of benzene was added 2.36 g

2346

TABLE i. Coordinates of Nonhydrogen Atoms of Cyanothioformic Morpholide Molecule

Atom X I" z

S 0 ~ NI S ~- C'; C s C 6 C z C:

0,64328(9) 1.0455(3) 0,8721(3) 0,8476(3) 0,7869(4) 0,8256(4) 0,9987(4) 0,8436(5) 1,0684(6) 0.9236(6)

0,3346(I) 0,0542(3) 0,2629(4) 0,6261(5) 0.3604(5) 0,5085(5) 0.2976(6) 0,1070(6) 0,2008(7) 0,0206 (7)

0,250 0,250 0,250 0,250 0,250 0,250 0,3078 (9) 0.t826 (8) 0,1846(9) 0,3064(9)

of chlorothioformic dimethylamide, and the whole was stirred for 7 h at 80~ The NaCI precipitate was separated on a centrifuge, and benzene was removed in vacuo. We obtained 2.5 g (52.7%) of compound (I) with mp 148-150~ Found: C 38.63; H 4.85; N 11.70%. CsHI2N2OS3. Calculated: C 38.69; H 4.84; N 11.28%.

2-Oxo-3-(dimethylaminothiocarbonylthio)-l-thia-4-azaspiro[4~5]dec-3-ene (II). Similarly, the reaction of 4.4 g of 2-oxo-3-mercapto-l-thia-4-azospiro[4.5]dec-3-ene sodium salt and 2,4 g of chlorothioformic dimethylamide gave 2.8 g (48.6%) of compound (If) with mp I12~ Found: C 45.45; H 5.60; N 10.55; S 33.44%. CIIHI6N2OSa. Calculated: C 45.87; H 5.60; N 9.92; S 33.40%. "

2~2-Dimethyl-5-oxo-4-thiono-l~3-thiazolidine (III). We dissolved 16.45 g of 2,2-dimethyl- 5-oxo-4-mercapto-l,3-thiazoline sodium salt in 70 ml of water and added 5 ml of conc. hydrochloric acid. The precipitated orange crystals were filtered, washed on the filter with water to pH 7, and dried at 50~ We obtained 8 g (55%) of compound (III) with mp 168-1700C. Found: C 36.97; H 4.95; N 8.90; S 38.82%. CsHTNOS=. Calculated: C 37.25; H 4.58; N 8.69; S 38.77%.

2-Oxo-3-thiono-l-thia-4-azaspiro[4.5]decane (IV). Similarly, treatment of 17.8 g of 2- oxo-3-mercapto-l-thia-4-azaspiro[4.5]dec-3-ene sodium salt with 8.3 ml of conc. hydrochloric acid gave orange crystals, which were washed on a filter with water and dried at 500C. Re- crystallization from a benzene:hexane mixture (4:1) gave 10.8 g (67.6%) of compound (IV) with mp 158~ IR spectrum, cm-1: vNH 3145, vC=O 1690, 6N~H 1530.

2,2-Dimethyl-5-oxo-4-thiono-3-(diethoxxphosphoryl)-l, 3-thiaz~ (V). To 2 g of 2,2- dimethyl-5-oxo-4-thiono-l,3-thiazolidine and 1.2 g of triethylamine in 50 ml of benzene was added 2.14 g of diethyl chlorophosphate with stirring, and the whole was heated for 10 h at 82=C. The precipitate of triethylamine hydrochloride was filtered, and benzene was removed in vacuo. The residue was chromatographed on AI203 (Brockman activity grade I), and benzene was the eluent. We obtained 2.7 g (73.0%) of compound (V) with nD 2~ 1.5217. Phos- phorus-31 NMR spectrum 6P 13 ppm. Found: C 37.02; H 6.00; P 9.86; S 21.33%. CgHI6NO~PS=. Calculated: C 36.36; H 5.42; P 10.42; S 21.57%.

2-Oxo-3-thiono-4-(dibutoxyphosphoryl)-l-thia-4-azaspi;0[4.5]decane (VI). This compound was obtained similarly from 2.23 g of 2-oxo-3-thiono-l-thia-4-azaspiro[4.5]decane and 2.28 g of dibutyl chlorophosphate in the presence of 1 g of triethylamine in 50 ml of benzene in yield 2.9 g (73.6%) with nD 2~ 1.5150. Phosphorus-31 NMR spectrum: 6P-12ppm. Found: C 47.56; H 7.08; P 8.29%. C16H28NO4PS 2. Calculated: C 48.31; H 7.17; P 7.87%.

Reaction of Solvate of Sodium Cyanodithioformate with Three Molecules of Dimethylforma- mide with Chloroacetone. To a suspension of 15.5 g (0.045 mole) of a solvate of sodium cyanodithioformate in 50 ml of chloroform was added 4.58 g (0.0495 mole) of chloroacetone and 3.92 g (0.045 mole) of morpholine. The tenoerature of the reaction mixture was increased from 17 to 43~ Then the reaction material was stirred for 6 h at %200C, and chloroform was removed in vacuo. The residue was diluted with a small amount of acetone, and the amorphous powder that settled on the bottom of the flask was filtered. From the filtrate was recorded 2 g (57.0% based on the starting morpholine) of cyanothioformic morpholide (VII) with mp !12-I14~ and 0.4 g (16.2%) of morpholine hydrochloride with mp 174-176~

2347

In the PMR spectrum of compound (VII), the methylene protons of the morpholine ring were manifested as a multiplet with a center at 4.05 ppm. IR spectrum, cm-~: vC=S 570, \'C-<)-C 1120, VCe N 2230. Found: C 46.70; H 5.14; N 17.80; S 20.51%. C6HsN2OS. Calculated:

C 46.14; H 5.18; N 17.93; S 20.52%. The IR spectrum of the recovered morpholine hydrochloride was completely identical to the IR spectrum of the certified specimen. Found: C 38.92; H 8.39; C1 28.16; N 11.34%. C~H~0CINO. Calculated: C 38.88; H 8.16; C1 28.69; N 11.33%. The bands in the IR spectra were assigned in accordance with [4].

I. 2.

3.

4.

LITERATURE CITED

J. Bahr and G. Schlietzer, Chem. Ber., 88, No. ii, 1771 (1955). J. Teller and H. Kibbel, German Democratic Republic Patent 209,827, Ref. Zh. Khim., Abstract No. 5 N 232 P (1985). N. V. Alekseev, Author's Abstract of Dissertation for Doctor of Chemical Sciences, Mosk. Gos. Univ., Moscow (1976). L. Bellamy, The Infrared Spectra of Complex Molecules, ist ed., Wiley, New York (1954).

REGIO- AND STEREODIRECTIVITY IN THE REACTIONS OF

ISOQUINOLINIUM YLIDES WITH UNSATURATED NITRILES

A. M. Shestopalov, L. A. Rodinovskaya, Yu. A. Sharanin, and V. P. Litvinov

UDC 541.63:542.91:541.49: 547.833.1:547.339.1

Reactions of isoquinolinium ylides with arylmethylenemalonitriles involve 1,3- dipolar cycloaddition, with the highly regio- and stereoselective formation of 2- aryl-3-benzoyl(or carbamoyl)l,l-dicyano-2,3-trans-l,2,3,10b-tetrahydropyrrolo[2, l-a]isoquinolines. In contrast, N-phenacylisoquinolinium ylide reacts with arylmethylenecyanothioacetamides differently, proceeding regio- and stereoselectively to give 4-aryl-2-hydroxy-3-(l-isoquinolinio)-2-phenyl-3-cyano-3,4-trans-l,2,3,4- tetrahydropyridine-6-thiolates.

The reactions of azinium ylides with unsaturated compounds have been utilized for the synthesis of physiologically active indolizines, benzoindolizines, and other cyclazines [1-6]. It has been found that these reactions proceed by 1,3-dipolar cycloaddition to give hydrogenated cyclazines, and are frequently accompanied by side rections involving elimina- tion, cycloelimination, or a variety of rearrangements [i, 2, 6]. There have been no reports up to the present time of the reactions of ylides with ~, a-unsaturated nitriles.

We have examined the reactions of isoquinolinium ylides with arylmethylenemalononitriles and arylmethylenecyanothioacetamides, and established their regio- and stereodirectivity. The isoquinolinium ylides were not isolated, but were generated directly in the reaction mixture by treating the azinium salts (Ia, b) in ethanol with an equimolar amount of triethylamine. The subsequent reactions of the azinium ylides (IIa, b) with the unsaturated nitriles followed differing routes, depending on the substituents present in the unsaturated compounds (Scheme i). The reactions of(Ila, b) with arylmethylenemalononitriles (IIla-g)-involved 1,3-dipolar cycloaddition regio- and stereoselectivitytogivethetetrahydropyrrolo[2,l-a]isoquinolines (IV) and (V) (Tables 1 and 2). The high regio- and stereodirectivity of these reactions was confirmed by physicochemical studies. The IR spectra of (IV) showed several asbsorption bands corresponding to deformational and stretching vibrations of the CONH 2 group at 1635- 1694 and 3180-3424 cm -I (Table 2), and the IR spectra of (V) showed absorption of high intensity for the C=<) group at 1685-1690 cm -I. In addition, in the IR spectra of all the

N. D. Zelinskii Institute of Organic Chemistry, Academy of Sciences of the USSR, Moscow. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. ii, pp. 2593-2599, November, 1990. Original article submitted November 30, 1989.

2348 0568-5230/90/3911-2348512.50 �9 1991 Plenum Publishing Corporation

synthesis of some substituted 1,3-thiazolines and 1,3-thiazolidines

Documents