reaction of α-amino acid esters with 2-ethoxy-4-thiolanones. synthesis of α-mercaptocarboxylic...

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3. M.G. Voronkov, V. B. Pukhnarevich, N. I. Ushakova, I. I. Tsykhanskaya, A. !. Albanov, and V. Yu. Vitkovskii, Zh. Obshch. Khim., 55, 94 (1985). 4. M.G. Voronkov and V. B. Pukhnarevich, Izv. Akad. Nauk SSSR, Ser. Khim., 1056 (1982). 5. L.I. Kopylova, M. V. Sigalov, ~. N. Satsuk, M. Chapka,u Chvalovsky, V. B. Pukhnare- vich, E. Ya. Lukevits, and M. G. Voronkov, Zh. Obshch. Khim., 51, 385 (1981). REACTION OF s-AMINO ACID ESTERS WITH 2-ETHOXY-4-THIOLANONES. SYNTHESIS OF ~-MERCAPTOCARBOXYLIC ACID AMIDES Yu. A. Davidovich, N. N. Semenova, K. K. Babievskii, and S. V. Rogozhin UDC 542.91:547.466'26 The preparation of ~-mercaptocarboxylic acids by the reported methods is difficult. For this purpose, in the present work we used 2-ethoxy-4-thiolanones (II) [i, 2] derived from mercaptoacetic (Ia) and R,S-a-mercaptopropionic acids (Ib) CO--O / I R--CH--COOH -~ (EtO)3C--R I-~H--CH ] I \ i SH S--C--OEt I (Ia, b) R 1 (Ua-d) R = H(Ia), Me(Ib); R = 1t ~ = H(IIa); R = H, R ~ - Me(IIb);R = Me, H~ = H(IIc) ; R = R x = Me(IId). Thiolanones (IIa) and (IIb) with one asymmetric site were obtained from acid (Ia), while (IIc) and (IId) with two asymmetric sites were obtained from (Ib). The diastereomer ratio for thiolanones (IIc) and (IId) found by integration of the PMR signals for the methyl group protons at C 5 in the thiolanone ring was I:I. Acylation of a-amino acid esters by 2-ethoxy-4-thiolanones occurs almost instantaneous- ly in ether CO--O R--CH~ / [ q- H2N--CH--COOR3 -~HS--CH--CONH--CH--COORa ' ' 1 S--CH--OEt R ~ H R 2 The experimental results are given in Table i. The ~-mercaptocarboxylic acid amides formed usually do not require further purification. EXPERIMENTAL Samples of mercaptoaeetic (Ia) and R,S-a-mercaptopropionic acids (Ib) freshly distilled in an argon stream were used in these experiments. The PMR spectra were taken on a Bruker HX-90 spectrometer at 200 MHz. The chemical shifts are given on the 6 scale relative to TMS. 2-Ethoxy-4-thiolanone (IIa). A mixture of 4.62 g acid (Ia), ii.i g ethyl orthoformate and 40 ml benzene was heated at reflux in an argon stream with zeotropic distillation of the alcohol formed. The decrease in volume of the mixture was compensated by the addition of benzene. After 2 h, the mixture was evaporated to yield 6.34 g (85.7%) thiolanone (IIa), bp 68-70~ (i mm) and nD 2~ 1.4814. Found, %: C 40.49, H 5.47~ S 21.35. C5H803S~ Calcu- lated, %: C 40.53, H 5.44, S 21.63. IR spectrum (neat, cm-l): 1780 (CO2R). PMR spectrum (without solvent, 6, ppm): 1.18 t (3H, CH3), 3.67 q (2H, CH20), 3.78 s (3H, CH2S), 6.57 s (IH, CH). A. N. Nesmeyanov Institute of Heteroorganic Compounds, Academy of Sciences of the USSR, Moscow. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2139- 2140, September, 1986. Original article submitted December 12, 1985. 0568-5230/86/3509-1951512.50 1987 Plenum Publishing Corporation 1951

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Page 1: Reaction of α-amino acid esters with 2-ethoxy-4-thiolanones. synthesis of α-mercaptocarboxylic acid amides

3. M.G. Voronkov, V. B. Pukhnarevich, N. I. Ushakova, I. I. Tsykhanskaya, A. !. Albanov, and V. Yu. Vitkovskii, Zh. Obshch. Khim., 55, 94 (1985).

4. M.G. Voronkov and V. B. Pukhnarevich, Izv. Akad. Nauk SSSR, Ser. Khim., 1056 (1982). 5. L.I. Kopylova, M. V. Sigalov, ~. N. Satsuk, M. Chapka,u Chvalovsky, V. B. Pukhnare-

vich, E. Ya. Lukevits, and M. G. Voronkov, Zh. Obshch. Khim., 51, 385 (1981).

REACTION OF s-AMINO ACID ESTERS WITH 2-ETHOXY-4-THIOLANONES.

SYNTHESIS OF ~-MERCAPTOCARBOXYLIC ACID AMIDES

Yu. A. Davidovich, N. N. Semenova, K. K. Babievskii, and S. V. Rogozhin

UDC 542.91:547.466'26

The preparation of ~-mercaptocarboxylic acids by the reported methods is difficult. For this purpose, in the present work we used 2-ethoxy-4-thiolanones (II) [i, 2] derived from mercaptoacetic (Ia) and R,S-a-mercaptopropionic acids (Ib)

CO--O / I

R--CH--COOH -~ (EtO)3C--R I -~H-- CH ] I \ i SH S--C--OEt

I (Ia, b) R 1

(Ua-d) R = H ( I a ) , M e ( I b ) ; R = 1t ~ = H ( I I a ) ; R = H, R ~ - M e ( I I b ) ; R = Me, H~ = H ( I I c ) ;

R = R x = Me(I Id ) .

Thiolanones (IIa) and (IIb) with one asymmetric site were obtained from acid (Ia), while (IIc) and (IId) with two asymmetric sites were obtained from (Ib). The diastereomer ratio for thiolanones (IIc) and (IId) found by integration of the PMR signals for the methyl group protons at C 5 in the thiolanone ring was I:I.

Acylation of a-amino acid esters by 2-ethoxy-4-thiolanones occurs almost instantaneous- ly in ether

CO--O

R--CH~ / [ q- H2N--CH--COOR3 -~ HS--CH--CONH--CH--COORa ' ' 1

S - - C H - - O E t R ~ H R 2

The experimental results are given in Table i. The ~-mercaptocarboxylic acid amides formed usually do not require further purification.

EXPERIMENTAL

Samples of mercaptoaeetic (Ia) and R,S-a-mercaptopropionic acids (Ib) freshly distilled in an argon stream were used in these experiments. The PMR spectra were taken on a Bruker HX-90 spectrometer at 200 MHz. The chemical shifts are given on the 6 scale relative to TMS.

2-Ethoxy-4-thiolanone (IIa). A mixture of 4.62 g acid (Ia), ii.i g ethyl orthoformate and 40 ml benzene was heated at reflux in an argon stream with zeotropic distillation of the alcohol formed. The decrease in volume of the mixture was compensated by the addition of benzene. After 2 h, the mixture was evaporated to yield 6.34 g (85.7%) thiolanone (IIa), bp 68-70~ (i mm) and nD 2~ 1.4814. Found, %: C 40.49, H 5.47~ S 21.35. C5H803S~ Calcu- lated, %: C 40.53, H 5.44, S 21.63. IR spectrum (neat, cm-l): 1780 (CO2R). PMR spectrum (without solvent, 6, ppm): 1.18 t (3H, CH3), 3.67 q (2H, CH20), 3.78 s (3H, CH2S), 6.57 s (IH, CH).

A. N. Nesmeyanov Institute of Heteroorganic Compounds, Academy of Sciences of the USSR, Moscow. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2139- 2140, September, 1986. Original article submitted December 12, 1985.

0568-5230/86/3509-1951512.50 �9 1987 Plenum Publishing Corporation 1951

Page 2: Reaction of α-amino acid esters with 2-ethoxy-4-thiolanones. synthesis of α-mercaptocarboxylic acid amides

TABLE 1

HSCHCONHCHC00R a f

R R 2

Starting a - amino acid ester

GlyO-t-Bu The same S-AlaOMe S-AlaO-t-Bu The same

S-ValO-t-Bu The same S-IleO-t-Bu S-LeuO-t-Bu S-MetOMe S-PheO-t-Bu S-TryOMe

R 2

H H

Me The same

>> i-Pr

The same 2-Bu i-Bu

MeSC2H~ PhCH2

CsH6NCH2

Ra

t-Bu The same

Me The same

>)

9

9 Me

t-Bu Me

E

H Me H H Me H

Me H H H H H

Mp,"C

89-91 50

62-64

59-60

[a]2D 0 *

-56,8 -10.2 -t2,9 +6,1 -2,3

+t6,0 -10,4 +28,t +44,2 +45,1

Chemical formula

CsHIsNO3S CgHITNO3S C6H~INO~S CgHITNOzS CIoHIgNO3S C,H2~NO~S CI2H25NO~S CI2H23NO3S CI~H23NO~S CsH,sNO~S2 CIsH2tN03S CuHi6N20~S

47,03 50,25 40,80 49,60 52,03 53,87 55,29 55,54 55,83 40,81 6t,43 57,~3

Found. r

H N

7,29 6,97 7,48 6,00 6,23 7;98 7,89 5,86 7,87 5,49 8,71 5,70 8,79 5,57 8,93 5,65 9,t7 5,79 6,38 6,00 7,58 4,69 5,32 8,66

t5,62 t4,25 18,24 t 4,44 t3,71 t2,54 11,95 11,74 tl,28 26,85 t0,81 11,t2

Calculated, ~o

c H N

46,67 7,35 6,81 49,29 7,81 6,39 40,64 6,26 7,9i 49,29 7,8t 6,38 5t,47 8,21 6,00 53,M 8,56 5,66 55, t4 8,87 5,34 55, i4 8,87 5,34 55,14 8,87 5,34 40,50 6,37 5,90 60,98 7,t7 4,71 57,51 5,52 9,59

i5,57 14,62 t8,24 14,62 13,74 t2,96 t2,27 12,27 t2,27 27,03 10,85 t0,96

" ( c i , dioxane).

Analogous procedures gave 2-ethoxy-2-methyl-4-thiolanone (lib) in 60% yield, bp 52-54~ (I mm), nD 2~ 1.4770. Found, %: C 44.41, H 6.25, S 19.81. CsHIoOaS. Calculated, %: C 44.43, H 6.21, S 19.76. IR spectrum (neat, cm-1): 1780 (CO2R).

2-Ethoxy-5-methyl-5-thiolanone (IIc) was obtained as a mixture of diastereomers in 88% yield, bp 68-70~ (I mm), nD 2~ 1.4735. Found, %: C 44.32, H 6.47, S 19.60. CsHI003S. Cal- culated, %: C 44.43, H 6.21, S 19.76. IR spectrum (neat, cm-l): 1775 (CO2R). PMR spec- trum (without solvent, 6, ppm): 1.18 t (3H, CH3), 1.53 d* (3H, CHa), 3.67 m (2H, CH20), 4.10 q (2H, CHS), 6.47 s (IH, CH).

2-Ethoxy-2,5-dimethyl-4-thiolanone (IId) was obtained as a mixture of diastereomers in 80% yield, bp 74~ (I mm), nD 2~ 1.4640, Found, %: C 47,71, H 7.18, S 18.64. C7H1203S. Calculated, %: C 47.70, H 6.87, S 18.19. IR spectrum (neat, cm-1): 1775 (CO2R). PMR spec- trum (without solvent, 6, ppm): 1.17 t (3H, CH3), 1.53 d* (3H, CH3), 1.87 s (3H, CH3), 3.68 m (2H, CH20), 4.23 q (2H, CHS).

Typical Procedure for the Preparation of a-Mercaptocarboxylic Acid Amides. An ethereal solution of 20 mmoles freshly distilled a-amino acid ester was added to a solution of 20 mmoles 2-ethoxy-4-thiolanone in an equal volume of ether. After some time, the mixture was evaporated in vacuum. The yield of the amides, which are oils crystallizing only with diffi- culty, was quantitative, as a rule.

The IR spectra taken neat or for KBr pellets have characteristic bands at 3315 • I0 cm -l (vNH), 2570 • 5 cm -I (vSH), 1730 • 5 cm- I (~CO2R), and several bands in the region from

1540 to 1670 cm-l.

*The P~iR spectrum signals are doubled and the signal intensity is I:i.

1952

Page 3: Reaction of α-amino acid esters with 2-ethoxy-4-thiolanones. synthesis of α-mercaptocarboxylic acid amides

CONCLUSIONS

e-Amino acid esters are readily acylated by 2-ethoxy-4-thiolanones to form the correspond- ing a-mercaptocarboxylic acid amides.

LITERATURE CITED

I. Yu. A. Davidovich, L. A. Davankova, S. V. Rogozhin, and N. N. Suvorov, USSR Inventor's Certificate No. 518,490; Byull. Izobret., No. 23 (1976).

2. Yu. A. Davidovich, h. A. Pavlova, and S. F. Rogozhin, Zh. Org. Khim., 14, 664 (1978).

INITIATED SYNTHESES OF BIFUNCTIONAL OXYGEN-CONTAINING

ORGANIC COMPOUNDS FROM CO AND H 2

Yu. B. Kagan,* V. Yu. Rumyantsev, E. V. Slivinskii, and S. M. Loktev

UDC 542.97:546.262.3-31:546.11:547.422

Heterogeneous catalytic syntheses of bifunctional compounds (e,m-diols and alkoxyalco- hols) from CO, H2, and a substituted acetylene (SA) containing a functional group (acetylenic alcohol or its ethers) were reported in our previous work [I]

CO n- H2 § IIC----CCH2OH -~ HO(CHj,~OH + H20

CO --~ H= --[ HC ---- CCH2OR -~ HO(CHJ,~OR + H20

A specially developed method was used to detect C~-Cl0 e,~-diols and methoxy- and tert-butoxy- alcohols [HO(CH2)nOR , where R is CH s or C(CH3) ~ and n = 4-7] in the reaction mixture.

Studies on the effect of the catalyst composition and the reaction conditions on the results of these syntheses showed that the synthesis of e,w-diols or alkoxyalcohols from CO, H~, and acetylenic alcohol or propargyl ether may be carried out at from ii0 to 170~ from 20 to 200 atm, and CO/H 2 ratio from 3:1 to 1:3 with 50-100% CO conversion to diols or alkoxyalcohols.

Comparison of these reactions with the synthesis of higher aliphatic alcohols from CO, H2, and acetylene [4] and of aromatic alcohols from CO, H2, and phenylacetylene [5] indicates that they fall into the same category of heterogeneous catalytic reactions which lead to the formation of various organic compounds containing (CH2)nOH or (CH2)n_ICHO fragments. The combined name of "induced carbon monoxide hydrocondensation" has been proposed for these reactions in accord with the concept of initiated heterogeneous catalytic reactions [6]~

The role of the SA in these reactions is limited to initiation. One of the most con- vincing arguments for this hypothesis is the result obtained in a series of special experiments carried out at II0-130~ I00 atm, and CO/H 2 = I:I, when the synthesis of higher aliphatic alcohols only from CO and H2 (i.e., without initiator) does not proceed at all. The primary complex is formed by means of the SA on the catalyst surface, possibly together with CO and H 2, This complex is the site of chain propagation. SA does not participate in further propa- gation of the chain.

The present results provide evidence on the other steps of the synthesis of bifunctional oxygen-containing organic compounds from CO, H 2, and a third component such as SA.

The following possible schemes for chain propagation in the synthesis from CO and H 2 have been discussed in the literature [7-10]: a) decomposition (disproportionation) of CO

*Deceased.

A. V. Topchiev Institute of Petrochemical Synthesis, Academy of Sciences of the USSR, Moscow. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2141- 2143, September, 1986. Original article submitted December 17, 1985.

0568-5230/86/3509-1953512.50 �9 1987 Plenum Publishing Corporation 1953