4932
\vILLIAX
E.
PARHAX,
EDWIN'r. HARPERAND RICHARDs. BERGER
VOl. Sd
[CONTRIBUTIOS FROM THE SCHOOL OF CHEMISTRY OF THE UNIVERSITY OF hfINNESOTA, ?dINNEAPOLIS, M I S N E S O T A ]
Heterocyclic Vinyl Ethers. XVIII.
Unsymmetrical 2,5-Diaryl-l,4-dithiadienes'
BY ~VILLIAM E. PARHAM, EDWIN T. HARPER^
AND
RICHARD S . BERGER
RECEIVED MARCH 5, 1960 Unsymmetrical 2,j-diaryl-l,l-dithiadienes have been prepared b y the acid hydrolysis of mixtures of Bunte salts derived from appropriate phenacpl halides The product ratios have been determined for the 2,4-diarylthiophenes which are obtained when 2-p-methoxyphenyl-5-pheny1-1,l-dithiadiene is decomposed, either thermally or by the action of peracid.
2,5-Diaryl-i ,J-dithiadienes are readily converted to %,4-diarylthiophenes by oxidation with pero x i d e ~ . Sulfoxides ~ have been shown to be intermediates4 in these transformations, and high yields of thiophenes are generally obtained. Diaryldithiadienes are also converted to thiophenes by the action of heat.3 Although little is known concerning the mechanism of this latter process, the reaction sequence
dithiadienes containing different aryl substituents depended on the acid hydrolysis of mixed Bunte salts VI1 and VIII. Two compounds of the
VIIIa, R = OCH, b, R=NO:!
VI1
ATR - fXR -
R
CHO
R
CHO-
1
dR +s
R& R
CHO
R
CHO
I1
I11 has been suggested3a to explain : (1) the lower tem-
perature required for such reactions when the dithiadiene ring contains an electron-withdrawing group; (2) the formation of thiophenes such as I11 instead of isomers with the electron-withdrawing substituent in the 3-position; (3) the importance of the aryl g r o ~ p s ,which ~ presumably further stabilize 11. The wTork described in this paper is concerned with the synthesis of unsymmetrical 2,5-diaryl1,4-dithiadienes, e.g. IV, and the conversion of IV,
IX
IV, R = OCHl X, R = NO2
XIa, R = OCH3
b, R = NO1
desired type were prepared : 2-p-methoxyphenyl-5phenyl-1,4-dithiadiene (IV) and 2-p-nitrophenyl-5phenyl-l,&-dithiadiene (X) . Three dithiadienes (total yield 45-50%) were found in each case and, as judged qualitatively from the weights of chromatographic fractions, the ratio of the three products was nearly statistical (approximately IX/IV/XIa = 1.012.2 1.1; IX/X/XIb = 1.0; 1.si- 0 3 ) . 2,5-Di-p-methoxyphenyl-l,&-dithiadiene(XIa) was also prepared (>joyoyield) by the acid hydrolysis of VIIIa. This new symmetrical diaryldithiadiene was further characterized by its conversion, by successive oxidation with peracetic acid, into the corresponding monosulfoxide (XII, 0,
0 2
XIV
by oxidation and pyrolysis, into the thiophenes V and VI. The application of the procedure of Baker and B a r k e n b d to the synthesis of 2,5-diaryl-l,4(1) P a r t of this work was supported by the Office of Ordnance Research, U. S. Army, Contract No. DA-11-022-Ord-2010, (2) F r o m t h e P h . D . Thesis of E. T. Harper, University of bfinnesota, 1959. ( 3 ) (a) W. E. P a r h a m and V. J. Traynelis, THISJ O U R N A L , 76, 4980 ( 1 9 5 4 ) ; ( b ) \\-, E . P a r h a m and V. J. Traynelis, ibid., 77, 68 (1935). ( c ) W. E P a r h a m , I . L'icholson and V. J. Traynelis, i b z i i , 7 8 , 830 (19.56). ( 4 ) H . H . Szmant a n d L . 5. Alionso, ibid.,79, 203 (1957). ( 5 ) W E. P a r h a m , G. I,. 0. Rlayo and B. Qadsby, z b i d , 81, 5993 (1959) (0) R . H. Baker a n d C . Barkenbus, { b i d , 68, 2G2 (1936). We also briefly examined t h e hydrolysis of xanthates a s a method f o r t h e synthesis of diaryldithiadienes; however, this method appeared less satisfactory.
Ar
s
XIa (Ar= p-CHBOCsHa-)
xv Y5"/'G), rnonosulfone (XIII, i6Yc) and disulforie
(XIV, 95y0). 2,5-Di-p-methoxyphenyl-1,4-dithiadiene (XIa) decomposed readily a t 19Oo into
Sept. 20, 1960
UNSYMMETRICAL
sulfur and 2,4-di-p-methoxyphenylthiophene (XV, 93y0 yield). This symmetrical thiophene was also prepared in high yield when the sulfoxide X I 1 was heated in dimethyl sulfoxide.4 The oxidation of 2-p-methoxyphenyl-5-phenyl1,Pdithiadiene (IV) with peracetic acid gave a mixture of isomeric sulfoxides (XVI) which were relatively unstable and were not separated. Further oxidation of these sulfoxides gave a mixture of monosulfones (XVII) or a single disulfone (XVIII). Either thermal decomposition of IV a t 185-215' or decomposition of XVI in dimethyl sulfoxide gave reasonably high yields of a product, m.p. -145150°, which had the composition calculated for the expected thiophenes V and VI (CI~HMOS). OCHBm
in 49% yield (product ratio V/VI is 1,'l.S). Since oxidation by peracetic acid (electrophilic attacks) should be more rapid a t the sulfur atom possessing the higher electron density, the preferential oxidation of the 4-sulfur atom in I V (scheme A preferred over scheme B) is consistent with a small sulfur 3d orbital resonance effect as indicated in IVa. It is of interest to note, in this connection, t h a t oxidation of 3-nitro-2,5-diphenyl-l,4-dithiadiene (XIX)3b gives the thiophenes X X and X X I in
XIX I
f
J
A1p0cH3 2P
CGHS
IV
C6H5
IsI 0 2
4933
~,~-DI~LR~'L-~,~-DITHIADIEK!ZS
XIXa
XVIII
I
c
0
4
C H 3 C 0 3 4 f r o m I")
isomeric monosulfones
XVII
V
VI
The mixture of thiophenes obtained by oxidation of IV was found' to contain V in 39% yield and VI
+
i
V
39$
J. O J .
VI 49Yc
(7) T h e independent synthesis of t h e thiophenes 1. (m.p. 103.5165.0°) a n d VI (m.p 144.5-145 5 ' ) and t h e method for determining the composition of mixtures containing V, V I and aibo I\' is described
respective yields of 46% and 31% (product ratio X X / X X I is 1.5/1). This observation suggests that the nitro group withdraws electrons, presumably by conjugation with sulfur 3p orbital electrons (XIXa), somewhat more effectively from the l-sulfur atom of X I X than from the 4-sulfur atom. These observations are consistent with the interpretation that: (a) sulfur 3p orbital conjugation is inhibited by the non-planarityga of the dithiadiene ring which reduces the conjugative effect of the nitro group and (b) sulfur 3d orbital conjugation, while not dependent upon planarity of the ringJSbis relatively unimportant. The possibility cannot be excluded, however, that the substituents exert a significant conjugative effect on both sulfur atoms as shown in XIXb. The thermal decomposition of IV produced, in addition to sulfur, the thiophenes V and VI in 39% and 27% yields, respectively. This distribution of products is difficult to interpret in view of uncertainties concerning the mechanism of the pyrolysis reaction. However, the product ratio of near unity (V/VI = 1.4/1) does not seem consistent with a simple polar mechanism of the type postulated in I -+ 111. The p-methoxyphenyl group of IV would be expected to exert a more profound effect upon such a polar transition state and to have a greater influence on the product distribution. in t h e accompanying paper b y W, E. P a r h a m a n d E. T . Harper, THIS JOURNAL, 82,493F (1960). (8) C. G. Overberger a n d R. W. Cummins, ibid., 76,4250 (l9S3). (9) (a) P. A. Howell, R. M. Curtis a n d UT.AT. Lipscomb, Acto C r y d , 7 , 498 (19.54); (b) G , E . Kimball, J . Chrm P h y s . , 8,188 (1940).
4934
~VILLIAME.
PARHAM,
EDWIX T. HARPER AND RICHARD s. BERGER
Vol. 82
Experimental
further recrystallization of the crude sulfdxide from methylene chloride-petroleum ether (b.p. 30-60'). hot A n d . Calcd. for ClsHlsOsSo:C , 62.76; H, 4.68. Found: solution obtained by heating (1 hr.) a mixture of p-methoxyC, 62.50; H , 4.76. phenacyl chloridelo (18.0 g., 0.0978 mole), sodium thiosulfate pentahydrate (24.5 g., 0.0988 mole) and distilled water T h e infrared spectrum of t h e product in S u j o l mull (30 ml.) was diluted with 9570 ethanol (50 ml.). The white showed strong absorption a t 1025 an.-', characteristic of Bunte salt, which crystallized when the solution was cooled, the sulfoxide group.13 was dissolved in a mixture of methanol (60 ml.) and distilled 2,5-Di-p-methoxyphenyl-l,4-dithiadiene1,l-dioxide water (30 ml.). Concentrated hydrochloric acid (60 ml.) (XIII).--A solution prepared from t h e sulfoxide X I 1 (0.32 was added t o this solution a t room temperature, and t h e g., 0.93 mmole, m.p. 138-145') in methylene chloride resulting mixture was stirred and heated a t the reflux tem(35 ml.) and 405% peracetic acid (0.47 ml., 2 . 9 mmoles) in perature for 21 hr. ethyl acetate ( 5 ml.) was allowed t o stand a t room temperaT h e reaction mixture was cooled in an ice-bath, and t h e ture for 20 hr. T h e solution was extracted with water ( 3 X yellow solid (13.07 g., 79$$ yield, m.p. 138-162') was 25 ml.), the organic layer was dried and t h e solvent was collected and recrystallized from acetic acid. There was removed. The crude monosulfone (0.25 E.. it?% vield. obtained 8.97 g. (54yc)of 2,5-di-p-methoxyphenyl-1,4-m.p. 199-204') was recrystallized from ce'nzene. Pure dithiadiene (XIa), m.p. 161-166". An additional quantity XI11 melted at 204.5-205.5". (2.73 g.) of X I a was obtained when the acetic acid mother Anal. Calcd. for C18Hi60&: C , 59.98; H , 4.48. Found: liquor was diluted with water, hut this material was not C, 60.10; H , 4.61. processed further. A sample of X I a (n1.p. 161--166') was The infrared spectrum of the monosulfone showed abchromatographed on alumina and recrystallized from sorptions character is ti^'^ of sulfones: 1315, 1120 cm.-l methylene chloride-petroleum ether ( b . p . 30-61)'); the (h-ujol); 1305, 1125 cm.-l (chloroform). pure product melted a t 167-169". 2,5-Di-p-methoxyphenyl-l,4-dithiadiene-l, 1,4,4-tetroxide Anal. Calcd. for C1SH160?S?:C, 65.82; H , 4.91. Found: (XIV).--A solution of t h e monosulfone XI11 (400 m g . , 1.11 C, 65.73; H , 4.93. mmoles) and 40Oj, peracetic acid (5 ml., 30 mmoles) in 2,5-Di-p-nitrophenyl-l,4-dithiadiene (XIb).--A mixture of acetic acid (80 ml.) was heated on the steam-bath for 2 hr. p-nitrophenacyl chloridell (m.p. 89-91', 6.7 g., 0.034 mole), The yield of crude disulfone (m.p. 249-254") obtained from the reaction mixture was 95yG (415 mg.). The melting sodium thiosulfate pentahydrate (5.4 g., 0.034 mole) and point was raised t o 252-255' by recrystallization of t h e water (15 ml.) was stirred vigorously and heated a t the product from acetic acid. reflux temperature for thirty minutes. T h e aqueous solution of t h e Bunte snlt was cooled slightly, diluted with Anal. Calcd. for Ci8H1606S2: C , 55.09; H , 4.11. Found: absolute ethanol (10 nil.), and concentrated hydrochloric C, 51.83; H , 4.20. acid (20 ml.) was added slowly. This misture was stirred T h e infrared spectrum of the disulfone showed absorptions aiid heated a t the reflux temperature for 3 hr. r\ rustcharacter is ti^'^ of sulfones: 1330, 1315 cm.-' (doublet), colored solid (n1.p. 147-1G7° dec., 5.93 g., 997; yield) 1120 cm.-' (Kujol mull); 1335, 1310 cm.-' (doublet), was obtained when the solution was cooled. Considerable 1130 c m - ' (Chloroform solution). loss accompanied the purification of this product by re2,4-Di-p-methoxyphenylthiophene(XV) tlia the Sulfoxide crystallization from diosane ( 16yGrecovery of material XII.--2,5- Di -p-methoxyphenyl- l,4-dithiadiene-1-oxide melting a t 200-202.5" dec.). Pure X I b melted 3t 205.5( X I I , 117 mg.) was dissolved in dimethyl sulfoxide (10 ml.), 207" dec. and the solution was heated on the steam-bath for 1 hr.' Bnnl. Calcd. for CIGH1oX!OIS:!: C, 53.62; H , 2.81. The misture was diluted with water (100 ml.) and cooled, Found: C , 53.92; H , 3.08. and slightly impure X V (90 mg., 90Sh, m.p. 167-213') Pyrolysis of 2,5-Di-p.methoxyphenyl-l,4-dithiadiene was collected. Recrystallization of this product from (XIa). 2.4-Di-p-methoxyphenylthiophene(XV).-A sample carbon tetrachloride gave 70 mg. (70"; yield) of yellowish needles, m.p. 216-220", which had an infrared spectrum of X I a (672 mg.) was placed in a side-arm test-tube fitted essentially identical with t h a t of an authentic sample of with a two-hole rubber stopper which supported a thermomX\-. The melting point was raised t o 217-319' by repeated eter and a gas inlet tube. The tube was flushed with nitrogen and immersed in a n oil-bath which was s l o ~ r l y recrystallization of the product from carbon tetrachloride (including decolorization with charcoal). T h e resulting heated t o 235'. The pyrolyszate was cooled, suspended in product was shown t o be identical, by mixed melting point benzene and chromatographed on a 15 X 450 m m . column and comparison of infrared spectra, t o 2,4-di-p-methoxyof alumina packed in petroleum ether (b.p. 60.68"). A n oily yellow solid (50 mg., 765% calcd. a s pure sulfur) phenylthiophene obtained by pyrolysis of X I a . Unsymmetrical 2,5-Diaryl-1,4-dithiadienesfrom Bunte was eluted with petroleum ether. 2,1-Di-p-methosyA. 2-p-Methoxyphenyl-5-phenyl-l,4-dithiadiene phenylthiophene (566mg., 9 3 5 yield, white crystals, m . p . Salts. (IV) .--A solution of sodium P-methoxyphenacyl thiosulfate 200-215') was eluted with solutions of benzene (37-5OL;;) (YIIIa) was obtained when a mixture of p-methoxyphenacyl in petroleum ether (b.p. 60-68'). The melting point of chloride'o (4.6 g., 0.025 mole), sodium thiosulfate pentathis product was raised t o 214-219' ( 7 9 R recovery) by one hydrate (6.3 g., 0.025 mole) and water (12.5 ml.) was stirred recrystallization from carbon tetrachloride and t o 218-2119' vigorously a t 75-85" for 30 minutes. An aqueous solution by further recrystallization from carbon tetrachloride. of sodium phenacyl thiosulfate ( V I I ) was prepared8 from Anal. Calcd. for ClxHlsOnS: C, 72.94; H , 5.44. Found: phenacyl chloride (3.9 g., 0.025 mole), sodium thiosulfate C, 72.66; H , 5.65. pentahydrate (6.3 g., 0.025 mole) and water ( 7 . 5 ml.). 2,5-Di-p-methoxyphenyl-l,4-dithiadiene-l-oxide (XII).T o these combined aqueous solutions mas added absolute The procedure of Szmant and Xlfonso.' was modified slightly. ethanol (15 ml.) and, slowly, concd. hydrochloric acid (30 T o a solution of 2,5-bis-p-methosyphenyl-l,4-dithiudieneml.). The resulting mixture was stirred and heated a t (XIa), 0.57 g . , 1.7 mmoles) in methylene chloride (25 ml.) reflux for 4 hr. The tacky solid t h a t separated a s the was added a solution of 405%,peracetic acidlz (0.66 ml., 4.0 solution was cooled t o room temperature was collected, mmoles) in ethyl acetate (6 ml.). After one minute, the washed with water and dissolved in a 5076 solution (200 mixture was extracted with water ( 3 X 25 ml.). T h e tnl.) of benzene in petroleum ether (b.p. 30-60") before organic layer was dried (CaCl?), cooled and filtered. There chromatograph:- on a 35-mm. column containing 250 g. o f was obtained 0.50 g . (probabll- wet weight, 85yc yield) of alumina. product, m . p . 141-144' dec. -In additional 0.32 g. (54YG) Three products were isolated by chromatograph>-. The of product (m.p. 138-145" dec.) \vas isolated by dilution of first of these, 2,5-diphenyl-1,4-dithiadiene ( I X , 0.53 g., the mother liquor with petroleum ether (b.p. 30-60") and 16ch yield, m.p. 95-117'; recrystallized from acetic acid, by concentration of the solution. An almost quantitative 0.33 g., 10yo, m.p. and mixed m . p . with authentic I X 8 yield of product melting a t 141-145O dec. was obtained b y 116-118"), was eluted with a 50%; solution of benzene in petroleum ether (b.p. 30-60'). T h e second product, (10) Prepared in 5 5 % yield ( m . p . 96.5-98 5 " ) by the procedure of eluted with 50 and 60cc solutions of benzene in petroleum A L . Wilds and T . L . Johnson, THISJ O U R X A L , 67, 287 (194n). ether ( h . p . 30-60°), was 2-p-methoxyphenyl-5-phen!.l-l,4-
2,5-Di-p-methoxyphenyl-1,4-dithiadiene(XIa).--A
, y
(11) P . Karrer and J. Schukri. Huh,. C h i m Acta, 28, 823 (194.i) , 1 2 ) Becco Chemical l)ivisiun, Food Alachinery and Chemical Cor:, , Buffalo 7 , iY Y .
3;,1 \./44(,'$ 11.) or methanol ( 7 5 5 , recovery, m . p . 135~-145', 23c$ \'1/32C,', T./46(,% 11'). Ethyl p-Methoxyphenacyl Xanthate.--.\ stirred solution of p-niethosyphenacyl chloride (5.6 g., 0.030 mole) in dry acetone (10 ml.) was added dropwise t o a suspension o f piitlissiurn ethyl xanthate (4.83 g . , 0.030 niole) iii dry
EDWINT.HARPER
Vol. 82
acetone (100 ml.). The precipitated potassium chloride was removed b y filtration, the solvent was removed by distillation at reduced pressure and the residue was recrystallized from ethanol. There was obtained 6.08 g. (80% yield) of ethyl p-methoxgphenacyl xanthate (m.p. 60-64'). Further recrystallization of this product from etherpetroleum ether (b.p. 30-60') gave yelltiw transparent plates melting a t 67.5-68.0'. Anal. Calcd. for C12H140:&:C, 53.31; H, 5.22. Found: C , 53.36; H , 5.58. Ethyl p-nitrophenacyl xanthate nas prepared from pnitrophenacyl chloride (6.00 g., 0.030 mole) by a procedure similar t o t h a t described above for ethyl p-methoxyphenacyl xanthate. The crude product (7.52 g., 93% yield, m.p. 81-87') was purified by recrystallization from etherpetroleum ether (b.p. 30-60") and the pure xanthate was obtained as fine white needles melting a t 88-89'. Anal. Calcd. for C11H1104NS2:C, 46.30; H, 3.89. Found: C, 46.80; H , 3.79.
[CONTRIBCTIOS FROM THE S C H O O L O F CHEMISTRY O F T H E UNIVERSITY O F MINSESOTA, LIISNEAPOLIS, M I S N E S O T A ]
Heterocyclic Vinyl Ethers. XIX.
Unsymmetrical 2,4-Diarylthiophenes'
BY \YILLIAM E. PARITAM AND EDWIN T. HARPER? RECEIVEDMARCH *5, 1960 The synthesis of 2-pliei1~l--l-p-1netl1~syp~ie1i~lt11i~~~liene (11) and 2-p-methosgplietiyl-4-phenglthiophene (111) is described by procedures which involve the high temperature sulfuiation of appropriate olefins. A by-product, believed t o be 2-(p-methox).phenyli-thieno ~%,3-b]thianaphthene ( S1, was isolated from the reaction of l-phen~-l-3-p-methoxyphenyl-2butene ( I Y ) and sulfur. The composition of mixtures of the isomeric thiophenes, either alone or containing 2-p-methoxy~ 1 h e i i p l - 5 - ~ h e n y l - l , 4 - ~ l i t l i i (~I~)~, can l i e nbe ~ determiiied conveniently by infrared spectroscopic analysis.
As part of our study3 of the formation of 2,4- ers recently have reported the synthesis of 2-pdiarylthiophenes from 2,%diaryl-l,-l-dithiadienes methoxyphenyl-4-phenylthiophene (111) by the (such as I), it became necessary to prepare 2phenyl-4-p-methoxyphenylthiophene (11) and 2fi-methoxyphenyl-&-phenylthiophene(111) and to C& devise a method for determining the composition of mixtures of I, I1 and 111. IV, R = H, R ' = OCH, V,R=OCHa, R ' = H 200"
I I , R = H , R'=OCHB 111,R z O C H 3 , R ' = H
The synthesis of 2,4diarylthiophenes has been studied in detail,4 but these methods have been generally limited to thiophenes in which the aryl substituents are identical. Schmitt5 and co-work(1) P a r t of this work was supported b y the Office of Ordnance re^ search, U. S. Army, Contract K O . D A - l l - 0 1 2 - 0 r d - 2 6 l l i . ( 2 ) From the P h . D . Thesis of E. T . Harper, Cniversity of hlinnesota, 1959. (3) W. E. P a r h a m and E. T . Harper, T H I S J O U K N A L , 82, 1931 (1900). 14) l a ) I.C d m y a i g u r , ,bid , 6 6 , lib4 (1544). i l l ) I' Ilemrrseman, h g Buu-Hoi, R . Koyer a n d A Chcutin, J ( h P i i i .So< , 2720 (1934). 1.5) (a) J. Schmitt, R . Fallard and M . SuqTict Liiili SLC. ciriin. I ~ r u , i u t , , 2 , 11-17 (1Y5Ci). ( b ) These workers reported their sthrling ketone, #-p-methoxyphenylpropiophenone, to melt a t 90-100" a n d the thiophene (111) t o melt a t 162'. Neither of these melting points are correct. P - p - ~ l e t h o x y p l i e n y l i ~ r o i ~ i o i ~ h e nmelts o n e a t 59-tiO', and the
reaction of V with sulfur, and we have eniployed this procedure (reaction of IV and V, respectively, with sulfur) for the preparation of the isomeric thiophenes I1 and 111. It became evident that the product obtained by Schmitt was not 2-9-methoxyphenyl-4-phenylthiophene (111) as described, but more probably the isomeric thiophene II.5b The olefins, 1-phenyl-3-p-methoxyphenyl-2 - butene (IV) and I-p-methoxyphenyl-3 - phenyl - 2 - butene (V) were synthesized, in 37% and 56% yields, respectively, by Grignard reactions. The dehydration of the alcohols VI1 and IX could logically give olefins with structures corresponding to A, B or C. Structure A (cis-2-butene) was assigned to olefin V (Ar = p-CH30C6H4-, Ar' = C6H5) in the following way. Structure C was eliminated on the basis of the infrared spectrum of thiophene 111 melts a t 115O. I t is reasonable t o assume t h a t Schmitt and co-workers started with t h e isomeric ketone p-phenyl-9-methoxypropioilhenone (m.p, 97') a n d prepared thiophene I1 ( m . p . 163').
