4-r-Azldo-3-t-methylsulfonamido-2-t-(4-methoxycarbonylbutyl) tetrahydrothiophene (Xll). Under conditions similar to those used in the preparation of XI, the reaction of 6.0 g (20.1 mmole) of VIII gave 4.0 g (77.2%) of XII in the form of a syrupy residue. Found: C 39.5; H 6.2; N 16.6; S 19.2%. CIoH:BN~O~S2. Calculated: C 39.3; H 6.0; N 16.7; S 19.1%.

LITERATURE CITED

1. S.D. Mikhno, T. M. Filippova, N. S. Kulachkina, I. G. Suchkova, and V. M. Berezovskii, Khim. Geterotsikl. Soedin., No. 5, 616 (1980).

2. T. Ogawa, T. Kawano, and M. Matsui, Carbohydr. Res., 31, 57 (1977). 3. H. Ohrui and S. Emoto, Tetrahedron Lett., No. 14, 2765 (1975). 4. S.D. Mikhno, T. M. Filippova, N. S. Kulachkina, I. G. Suchkova, and V. M. Berezovskii,

Khim. Geterotsikl. Soedin., No. 5, 616 (1980). 5. S.D. Mikhno, T. M. Filippova, I. G. Suchkova, and V. M. Berezovskii, Khim. Geterotsikl.

Soedin., No. I0, 1339 (1983).

FORMATION OF UNCONDENSED BINUCLEAR HETEROCYCLIC COMPOUNDS

IN THE THIO-CLAISEN REARRANGEMENT OF HETEROAROMATIC SULFIDES

A. V. Anlsimov, S. M. Panov, V. F. Sizol, S. A. Nepogod'ev, and E. A. Viktorova

UDC 547.728.1:547.732

Allyl hetaryl sulfides with an allyl fragment that is part of a heteroaromatic ring undergo a [3,3]-sigmatroplc rearrangement when they are heated in various solvents, as a result of which uncondensed binuclear heterocyclic compounds are formed. On the basis of kinetic data it was shown that the inclusion of the vinyl or allyl fragment of a sulfide in the composition of the heteroaromatic ring hlnders the rearrangement more, the higher the aromatic character of the hetero- ring.

As demonstrated in [i, 2], the thio-Claisen rearrangement is a promising method for the synthesis of binuclear condensed heterocyclic compounds, and when various allyl aryl and allyl hetaryl sulfides are used in it as, for example, substrates, one can produce thiophene and thiopyran derivatives that are difficult to obtain. A comparison of the reaction con- ditions, the yields of reaction products, and the kinetic parameters of the rearrangement of various sulfides with various aromatic or heteroaromatic rings in the vinyl fragment makes it possible to conclude that a decrease in the aromatic character of the ring that includes the vinyl fragment of the substrate facilitates the thio-Claisen rearrangement [3].

In the present research we accomplished the thio-Claisen rearrangement of thenyl 2-thienyl sulfide (I), =henyl 2-benzofuryl sulfide (II) furfuryl 2-benzofuryl sulfide (III), benzofurfuryl 2-thienyl sulfide (IV), and benzyl 3-benzofuryl sulfide (V), in which both vinyl and allyl fragmen=s are included in the composition of the heteroaromatic systems. Sulfides I-V were obtained by condensation of heteroaromatic thiols with the corresponding halomethyl derivatives of heterocycles in aqueous alkali solution. The physicochemical and spectral characteristics of sulfides I-V are presented in Table i.

When sulfides I-IV are heated in various solvents (m-xylene, dimethylformamide, and N,N-dimethylaniline) at 200-250~ they undergo rearrangement to give 3-(2-methyl-3-thienyl)- 2-thiophenethiol (VI), 3-(2-methyl-3-thienyl)-2-benzofuranthiol (VII), 3-(2-methyl-3-furyl)- 2-benzofuranthiol (Vlll), and 3-(2-methyl-3-benzofuryl)-2-thiophenethiol (IX), respectively, which are readily isolated from the reaction mixtures with aqueous alkali. Sulfides Vla- IXa, which, in contrast to the thiols, are readily distilled in vacuo without decomposition,

M. V. Lomonosov Moscow State University, Moscow 117234. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. i0, pp, 1348-1351, October, 1983. Original article submitted March 28, 1983.

1072 0009-3122/83/1910- 1072507.50 �9 1984 Plenum Publishing Corporation

TABLE i. Properties of Heteroaromatic Sulfides

,~ bp, "C = = ( I ram)

n D2o d,7 ~ PMR spectrum, Found, % IEmpirical ppm c H s ]formula

I ! 115--116 [,637811,( 02~

II/148--t52 --* t --

V 144--146ti,6970 / --

I 7,00 (3H,m, thiophene); 151,4 3,9 6,80 (3H, m, thiophene); ! 4,04 (2H, s, CH2) 7,30 (4H, m,arom3: -- -- 6,90 (3H, m, thiophene); 6.75 (1H, s, 3-benzo- furan); 4.15 (2H, s, t~)

17,30 (4H, m, atom ) ; I 6,7, 4,5 7,05 (IH, m ~-fu-

I ran~; 6,60 (ill, s, 3-benzofuran); 6,10 (1H, m, ]3-furan); ); 5,93 (1H, m, 5-furan); 4.03 (2H, s, CH2) CH2) 7,27 (4H, m, arom); , 63,7 4,2 6,87 (3H, m, thiophene); 6,30 (1H, s, B-benzo- I furan); 3,95 (2H, s,

1 CH2) 7,27 (2H, m, atom ); 75,2 5,2 6,53 (1H, s B-benzo-

furan); 4,03 (2H, s, C~2)

43,8 tCgHaSz

25,9 [CI,~H ioO ~2

- - ICl~HloO :S

25,7 CteH,oOS:

13,6 CmHI2OS

1

*mp. 48-49.5~

Calc, O/o

C H S

50,9 3,7 45,3 55

-- -- 26,0 53

67,8 4,4 -- [31

53,4 4,1 26,0156'

75,0 5,0 13,3152

were obtained by methylation of thiols VI-IX with methyl iodide in alkaline media. The presence of characteristic signals of thiol and methyl groups in the PMR spectra of the isolated thiols and the absence of the corresponding signals of 8 protons of heteroaromatic rings that are present in the spectra of the starting sulfides (Table 3) constitute evidence that sulfides I-IV undergo transformations via the normal scheme of the thio-Claisen re- arrangement:

j H.. ,>%.. , .

i l l! t! I{ .. . . . . . . . . . . . ~l! :: :

r : =~-=l ~ : . i -~-=-:! H !

~ ' ! ' - - . . . . L L ~1 "I ......... [~ CH. " S / ~ ' S CIIz i -~ / " . . ~ a ~ / " - " - S S l l S "SCH~ ~

V1 V I a

In order to compare the reactivities of sulfides I-IV we determined the kinetic param- eters of their rearrangement. The first-order character of the reaction, the negative en- tropies of activation, and the absence of a clearly expressed dependence of the rate con- stants on the polarity of the solvent make it possible to classify the rearrangement of these sul- fides as a concerted [3, 3]-sigmatropic process. According to the rearrangement rate con- stants obtained (Table 2), sulfides I-V can be arranged in the following order with respect to their reactivities: III> IV> I >V.

An increase in the degree of aromatic character of the heteroring in both the vinyl and allyl fragments of the substrate hinders rearrangement, whereas replacement of the thio- phene in sulfide I by the less aromatic benzofuran ring facilitates the rearrangement to a great degree if the heteroring in the allyl fragment rather than in the vinyl fragment is replaced. Sulfide V, the allyl fragment of which is included in the composition of the benzene ring, does not undergo rearrangement even when it is heated to 250~ The rearrange- ment rate constants under identical conditions are greater by a factor of approximately

1073

TABLE 2. Some Kinetic Parameters of the Rearrangement of Sulfides I-IV

C o m -

p o u n d Solvent Temp., "K

K X 10 4 sec-I Correla- M/mole tion co- s efficient

I

II

III

IV

m -Xylene DMF

rn -Xylene N,N-DMA DMF N,N-DMA DMF m-Xylene N,N-DMA DMF

483 473 483 478 463 473 463 483 472 463

0,11 1,00

0,04 0,46 0,67 0,40 0,95 0,52 0,40 1,30

0,778 0,856 0,780 0,839 0,912 0,875 0,924 0,870 0,896 0,926

151_+9 143_+9 147_+9 88_+8

139_+9 92_+8

134--+9 i26-+9 84-+7 92_+8

- A S ~' , en

10 8

I0 38 9

35 1l I9 39 32

TABLE 3. arrangement and of Their Methyl Derivatives

Compound

Properties of the

VI

Methyl 2-[3-(2- tne thvl- 3- thienyl)]- sulfiffe (Via)

VI1

Methyl 2-[3-(2- methyl- 3- thienyl)]- benzofuryl sulfide (VIIa)

VIII

Methyl 2-[3-(2-methyl- 3- furyl)]benzdfuryl sulfide (VIIIa)

IX

bp, "C (i ram)

118--120

i50--152

- I

110--112

150--152

llD20

1,6837

1,6540

1,6235

1,6532

Thiols Isolated in

PMR spectrum

the Thio-Claisen Re-

Methyl 2- [3- (2-methyl - 3- benzofuryl)]thienyl sulfide (IXa)

6,5--7,3 (4H, m, thiophene);3,15 (Ill. s, SH); 2,27 (3It, s, C[-[3) 6,5--7,3 (4H, m, thiophene); 2,45 (3tl, s, SCH3); 2,27 (gtt, ~, CH3)

7,0--7,4 (5H, m, arom,); 6,85 (1H, B-thiophene) 3,4 (IH, s, SH); 2,3 (3H,S, CH~) 7,0--7,4 (5H, m,arom .); 6,85 (lH, m, B-thiophene); 2,5 (3H, s, SCHa); 2,3 (3H, s, CHa)

7, l--7,4 (4H, m. atom ); 7,0 (I}t, m, a - fu ran ) ; 6,2 (1H, m, ~.furan); 3.4 (114, s, SH); 2,3 (3H, s, CH3) 7,1--7,4 (4H, m, arom,); 7,0 (1H, m, a - furan) ; 6,2 (IH, m, ~-furan) 2.45 (3H, s, SCHa); 2,3 (3H, s, CH3) 7,5--6,8 (6H, m, atom., thiophene) 3,35 (11.t, s, SIq); 2,3 (3H, s, CHa) 7,5--6,8 (61I, m, arom, thAophene); 2,,t5 (3H, s, SCHa); 2,3 (3H, s C1f3)

Yield, %

31

35

33

30

TABLE 4. Mass Spectra of Some of the Sulfides

Compound m/z(l,%)

II III V

Vlla

Villa

246 (6); 149 (4); 121 (5); 98 (9); 97 (lO0); 77 (9) 230 (6); 149 (4); 121 (6); 82 (8); 81 (I00) 240 (9); 150 (4); 149 (4); 121 (5); 92 (12); 91 (I00) 226 (20); 211 (i0); 193 (7); 179 (9); 158 (37); 144 (31); 143 (34); 111 (26); 97 (100) 244 (2); 229 (2); 179 (16); 178 (I00); 164 (16); 163 (98); 131 (9); 119 (24); I03 (13); 91 (29)

three for sulfide III than for sulfide II, whereas the rate constants differ to a smaller extent in the case of a change in the degree of aromatic character of the heteroring in the vinyl fragment (compare sulfides I and II, Table 2). Thus a change in the degree of aromatic character of the ring that includes a vinyl fragment has a smaller effect on the reactivity of the sulfide than a change in the aromatic character of the ring that contains an allyl fragment.

The rearrangement of hetaryl (hetarylmethyl) sulfides significantly increases the synthetic potential of the thio-Claisen rearrangement and can be used to obtain uncondensed binuclear hetarocycllc compounds~ viz., furan and thiophene derivatives.

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EXPERIMENTAL

The PMR spectra of solutions in CCl~ were recorded with a Varian T-60 spectrometer with hexamethyldisiloxane as the internal standard. The mass spectra were obtained with an AE-I MS-30 spectrometer at 20~ (direct introduction of the samples) and an ionization energy of 70 eV. The kinetic measurements were made by the method described in [4]. The purity of the synthesized sulfides I-V and Vla-IXa was monitored by gas--liquid chromatography (GLC) with an LKhM-8MD-I chromatograph with a 200 • 0.4 cm column packed with 5% SE-30 on a Chromaton N support; the column temperature was 180~ and the carrier gas was helium (flow rate 30 ml/min).

Synthesis of Starting Sulfides I-V. An aqueous solution of lithium thiolate was ob- tained by the successive action on thiophene or benzofuran n-butyilithium, sulfur, and water [5]. 2-Chloromethylthiophene [6] (sulfides I and II), furfuryl bromide [7] (sulfide II!)~ benzofurfuryl bromide [7] (sulfide IV), or benzyl chloride (sulfide V) was added to the thiolate solution, and the reaction mixture was stirred for several hours. It was then extracted with ether, and the extract was dried with magnesium sulfate. After removal of the ether by distillation, the sulfide was distilled in vacuo.

Rearrangement of Sulfides I-IV. A solution of 4 g of the sulfide in 30 ml of N,N-di- methylanillne was heated in an argon atmosphere at 220-250~ for 1.5-2 h in a sealed ampul, after which the mixture was cooled and diluted with ether, and the ether mixture was washed with 10% hydrochloric acid solution to remove the amine. Evaporation of the ether gave the unchanged sulfide. The aqueous alkali solution of the thiolate yielded the thiol after dilution with 10% hydrochloric acid and extraction with ether~

To obtain S-methyl derivatives of the thiols, a fivefold excess of methyl iodide was added to an aqueous alkali solution of the thiolate, and the mixture was stirred at 20~C for 2 h. The sulfides were extracted with ether, and the ether extracts were dried and dis- tilled ~n u~cuo. The properties of the thlols and sulfides are presented in Table 3o

LITERATURE CITED

i. G.B. Bennet, Synthesis, No. 9, 589 (1977). 2. A.V. Anlslmov and E. A. Viktorova, Khim. Geterotsikl. Soedin., No. 4, 435 (1980). 3. A.V. Anisimov, V. F. Ionova, V. K. Govorek, V. S. Babaitsev, and E. A. Viktorova,

Dokl. Akad. Nauk SSSR, 244, 362 (1979). 4. S.M. Panov, A. V. Anisimov, and E. A. Viktorova, Khim. Geterotsikl. Soedino, Noo 2,

i81 (1982). 5. Ya. L. Gol'dfarb, M. A. Kalik, and M. L. Kirmalova, Zh. Obshch. Khim., 29, 2034 (1959). 6. Organic Syntheses [Russian translation], Collective Vol. 4, Inostr. Lit., Moscow

(1953), p. 537. 7. J.E. Zenetti, J. Am. Chem. Soc., 4_99, 1065 (1927).

1075