3410
HANS-DIETER
BECKER,G E R A R D J L~IKCII,,A N D GLENA . RUSSELL
a s an ether-insoluble residue. From the ether solution 118 mg. (48(7;) of YIIa crystallized after evaporation of the solvent. VIIa. Reaction 7c.-Compound Va ( 5 0 mg., 0.13 mmole) and 100 nig. of potassium t-butoxide were dissolved in 0.4 nil. of t-butyl alcohol and 1.6 nil. of DMSO. The reaction mixture was kept under nitrogen a t 75" for 2 hr. .;\ddition of 10 nil. of water yielded an emulsion which was shaken with 3 nil. of ether. The crystalline product which separated from the ether-water mixture was separated after 2 days. Recrystallization from hot ethanol gave 19 mg. (48Sb) of I - I I a , m . p . 103'. The infrared suectrum was identical with that of compounds prepared in . . reactions 7, 7a, and 7b. VIIb and IVb i R ' = R = C6H,). Reactions 4a and 7a.-Diphenyltnethane (1.68 g., 10 miiioies) and 1.12 g. of potassium tbutoxide were dissolved under nitrogen a t 60' i n 15 nil. of DMSO. Benzaldehyde (1.0 g., 10 mrnoles) in 5 ml. of DMSO was added over a period of 15 min. The color of the s(J1utiotl changed from red to green during the addition. T h e mixture was kept a t room temperature for 30 miri. after which time 100 nil. of ice-water was added. The mixture was extracted with 300 nil. of ether. Separation and evaporation of the ether layer yielded a yellow oil which contained colorless crystals. The oily residue W:IP treated with few cc. of ether arid filtered, yielding 155 mg. of I\'b (5(,ij. The m . p . after recryst:illization from a chlorofor in-methanol mixture was 195-1 96 O . Annl. Calcd. for C??Hp?OS (334.40): C , 79.01; H , (i.fi3; S, 9.52. Found: C, 78.98; H , fj.72; S , 9.21. The oil obtained after evaporation of the filtrate was heated with ethanol, yielding 430 mg. of \ . 1 I b (13.X' L ) , ni.p. XX-90"; lit.20 m.p. 87-89"; 92-93". Annl. Calcd. for C J ~ H , ,(270.35): C , 93.29; H , (i.71. Found: C , 93.39; H , 6.94; nlol. wt. (dioxane), 291. VIIc ( R ' = C,H,, R = 3,4-CH202CeHa).Reaction 7a.-Diphenyltiiethane (1.68 g., 10 mnioles) and 1.12 g. of potassiuin t-butoxide were dissolved in 15 1111. of DMSO and 60". From a buret 1.5 g. of piperonal (10 mnioles) in 5 nil. of DMSO was added over a period of 13 niiii. The reaction mixture, which turned red and finally green-brown, was kept a t room teinperature for 30 min. hfter addition of 100 nil. of ice-ivater the niixture was extracted with 600 nil. of ether. Evaporation of tlie ether layer yielded a11 oil which upon treatment with ethanol gave 600 rng. of crude YIIc (19';). The substance was recrystallized from a hot ethanol-chloroforrn mixture t o give V I IC, 111.p. 123-125'. i l n a l . Calcd. for C22H1802 (314.6): C , 84.05; H , 5.77. Found: C , 83.87; H , 5.89. Condensation between p-Anisaldehyde, DMSO, and Cyclohexanone. (VIII).-p-.knisaldehyde (2.8 nil., 20 inmoles) was added t o a solution of 2.75 g. of potassium t-butoxide in 15 nil. of DMSO a t 60' under nitrogen. After 5 niin. a t 6 0 ° , 2 t n l . of cyclohexanone (20 inmoles) was added to the brown solutiori. After 3 0 min. a t 60", 100 g . of ice was added to the reaction mixture and the mixture extracted with 200 1111. of ether. From the ether solution 380 mg. of \.I11 separated (6.5' L ) , rn.p. 275'. ~
~~~~
(20) W . Schlenk and E Bergrnann, A n n , 463, 1 ( 1 9 2 8 ) ; H. Grabbe, a n d F Ulrich, Be?., 67, 1983 ( 1 9 2 4 ) .
[CONTRIBUTION FROM
THE
K
Ziegler,
ir01.
s.5
Recrystallization from ethanol by the addition of a little chloroThe infrared anti n.1n.r. form gave a compound, 111.p.275-276'. spectra were consistent with structure 1'111. The r1.m.r. spectrum failed to show a methyl group other than that of the p inethoxy group. Anel. Calcd. CltiH~03S(294.34): C , 65.29; H , 7.53; S, 10.82. Found: C , 65.31; H , i.69; S, 11.00. Di-9-fluorenylphenylmethane.-Benzaldehyde (0.3 nil., 3 inmoles) was added t o a solution of 499 mg. of fluorene ( 3 inmoles) in 7.5 ml. of DMSO containing 0.37 g. of sublimed potassium 1butoxide under a nitrogen atmosphere. The red solution turned blue after 6 min. at room temperature. A t this time 100 nil. of water was added and the resulting solution extracted with 600 nil. of ether. Evaporation of the ether solution gave crystals which after recrystallization from a mixture of ethanol, and chloroform yielded 74 ing. (9',L) of di-9-fluorenylphenyltnetharie, 1n.p. 230", lit.'3 239". The n.m.r. shows an A2B pattern of methine protons with the benzylic proton absorbing as a triplet ( J A =~ 7.6 c.p.s. a t 60 Mc./sec.) a t T = 6.8 and the 9-fluoreriyl protoiis absorbing as a doublet at T = 5.0. Di-9-fluorenyl-p-methoxyphenylmethane .-p-Anisaldehyde (0.4 m l . , 3 rn~noles)was added t o 499 m g . ( 3 mtnoles) of fluorene dissolved in 7 . 5 nil. of DMSO under nitrogen. The addition of 366 rng. of potassium t-butoxide resulting in warming and the develop~nentof a red color which turned to a blue (reminiscent of fluorenyl ketyl) after 15 niin. When the blue color developed, 100 inl. of water was added t o give a yellow emulsion which was extracted with 200 ml. of ether. Evaporation of the ether extract to 30 m l . yielded 400 ing. ( 70r!L,) of di-9-fluoretiyl-p-riietli( phenylmethanc, m . p . 230-232'. The n.1ii.r. spectrum app unequivocal for this structure since it shows an A?B pattern for the three methine hydrogens. The p-methoxybenzl-I. hydrogen appeared as a triplet a t T = 6.8, J ~ =B 6.9 C . P . S . a t 60 Mc./sec., area = 1.0; the 9-flu rogens absorbed as a doublet a t T = 5.05, area = 2.0 protons a t T = 6.4, area = 3.0; p-methoxyphenyl pro ) a t T = 3.6, area = 4.0; and fluorenyl ring protons as a complex absorption between 420 and 480 c.p.s. relative t o tetrarnethylsilarie, area = 16. l-Benzoyl-2-phenyl-3-(methylsulfonyl)-propane. -To 0.53 g. of benzaldehyde ( 5 inmoles) in 15 ml. of DMSO, 1.12 g. of potassium t-butoxide and 0.54 g. ( 5 inmoles) of acetophenone were added. After 1 hr. a t 30-35', 100 ml. of water was added and the resulting emulsions extracted with 300 nil. of ether. The ether was evaporated t o yield an oil which did no lize. hfter 10 days in an open vessel, the oil cr. 70 rng. (15'/;) of l-benzoyl-d-phenyl-3-( methylsulfony1)-propane, rn.p. 126-126', recrystallized from ethanol. The infrared showed sulfone and carbonyl absorptions. The n.m.r. (60 Mc./sec.) showed one methyl group ( T = 7.5j, area 3.0 units; aromatic protons 438 to 480 c.p.s. relative t o tetramethylsilane, area 10.1 units; and a complicated 5-proton absorption (area = 5.1 units) between 155 and 266 C.P.S.relative to tetramethylsilane. The complexity of the 5-proton area is undoubtedly due t o tlie presence of two methylene groups attached to an asytnrnetric methine group. A n d . Calcd. C17H1803S (302.37): C, 67.54; H , 0.00; S, 10.60. Found: C, 67.78; H , 5.94; S, 10.30.
DEPARTMENT O F CHEMISTRY, IO\VA
STATE
UNIVERSITY, .kMES, IOWA]
Preparation and Pummerer Rearrangement of p-Ketosulfoxidesl.2 BY HANS-DIETER BECKER,(>ERARD J . ~ I I K OAL N D, GLENA.
RUSSELL~
RECEIVED MARCH1, 1968 The preparation of 0-ketosulfoxides from aromatic esters and ditnethyl sulfoxide is described. Acid-catalj-zed rearrangement of these p-ketosulfoxides leads to the formatinn nf methyl hetnirnercaptals of a-ketoaldehpdes. The riiechanistn of this rearrangement is discussed.
Introduction The carbanion formed in solutions of dimethyl sulfoxide (DAISO) containing bases such as sodium hydride or alkali metal alkoxides, undergoes reaction with carbonyl compounds such as aldehydes or ketone^.^ B-Hydroxysulfoxides formed in this manner can be (1) Reactions o f Resonance Stabilized Anions. X ( 2 ) T h i s work was s u p p i r t e d h y grants from t h e Alfred I' Sloan I'ounda-
H
H H+
~
CH1SOCH2- + RC=O
+
IIV-CH*-OAc
DN
\
-+ >W-CCHs
I1
CHa
+ CHzO
0
volving a n intramolecular rearrangement of the chlorine atom seems well substantiated since Truce, Birum, and McBee found that in the presence of molecular bromine that the rearrangement to give the a-chlorosulfide proceeded normally. 13b T h e rearrangement of the chlorosulfonium chloride has been pictured as involving C1 K-S-CH2- as an intermediate followed by a "downhill
+
ride of the chloronium ion from sulfur to carbon on an electron In the case of rearrangements involving the use of acetic anhydride the Pummerer rearrangement seems to present no mechanistic problems and can be readily formulated as involving a cyclic i r ~ t e r r n e d i a t e . ' ~How~ 0 CH3 H C '' I I RCHzSOR' RC,HO, RCFt 0 + OAc--' S$ HOAo ?+ AcaO R' R' 4 RCH(SR')OCOCHa ever, the rearrangements of sulfoxides directly to hemimercaptals under the mild conditions employed in this work, as well as the analogous rearrangements observed in the recrystallization of 1-propyl-3-ethyl-1H-pyrimido [5,4-b][ 1,4]thiazine-:!,4,7-(3H,6H,8H)-trione 3-oxide
+
-
+
from methanol, ethanol, acetic acid, or water with the formation of a-methoxy, a-ethoxy, a-acetoxy, and a-hydroxy derivatives,12 is not as easily understood. In our work the need for catalysis by a mineral acid certainly suggests protonation prior to rearrangement. The fact that Ia rearranges readily under conditions OH RCOCHzSOCHt
+ H + -+
R-C-CH2-&CH.
(Iv)
II
0
where I b is stable, strongly suggests the loss of a proton from the methylene group prior or during rearrangement. In fact, Schroeder and Dodson have reported OH I v -+ R C C H S C H ~
I1
+
0
examples of base-catalyzed "rearrangements" in the pyrimidothiazines.l 2 Intermediate V could rearrange directly to the a-hydroxysulfide by the migration of the HO+ moiety. Alternately, V could ionize to RCOCH=SCH3 + as suggested by Schroeder and Dodson.12 A third alternative is t h a t V undergoes nucleophilic attack by the solvent. We are currently attempting R-C-CH=S-CH,
f
b
-RC-CH-S-CH, II I
+ H,O
0 OH H 9% H to ascertain the source of the hydroxy group in the final product by isotopic labeling.
Vol. 83
If the conversion of ketosulfoxides to herniniercantnls does indeed involve a true intramolecular rearrangement without participation by the solvent, an intcrmediate or transition state of the type would he inH
0-
/ \,.-
KCOCH--S-CH~
dicated. This would seem to have considerable irnplication in regard to the stereochemistry of carbanions a to the sulfone group. T h e observation that such carbanions can maintain the stereochemistry of the original alkyl substituent'j could be explained if the carbanion has the cyclic structure.
Experimental Reagents.-Dimethyl sulfoxide (Crown Zellerbach Corp.) was dried over calcium hydride and distilled at 1 mm. (bath temperature G O " , b.p. 35') immediately before use. Ethyl benzoate and methyl salicylate were distilled and methyl p-anisate was recrystallized before use. The potassium t-butoxide was vacuum sublimed. w-( Methylsulfiny1)-acetophenone ( I a ) . -Potassium ( 2 g . , 51 mg.-atoms) was dissolved in 50 mi. of refluxing t-butyl alcohol. After cooling to room temperature, 50 1111. of DMSO was added and the solution vacuum distilled (pressure about 2 mtn., bath temperature 65-70') using a \-igreux column until pure DMSO started distilling ( b . p . 43'). Approximately 50 ml. of distillate was collected. T o the partially solid residue ethyl benzoate ( 7 . 5 g., 50 mmoles) was added dropwise a t room temperature. The reaction mixture was agitated by a stream of d r y , oxygenfree nitrogen for a total of 4 h r . The solvent was then removed by vacuum distillation ( -1 nim. pressure, bath temperature --0 i a ) during 1.5 hr. Ether (100 ml.) and water (50 m l . ) were added t o the oily yellowish residue a t room temperature. T h e aqueous layer was separated and acidified t o p H 5-6 (indicator paper) with a mixture of 5 mi. of concentrated hydrochloric acid and 20 ml. of water. The aqueous solution was extracted with five 200-ml. portions of chloroform. Evaporation of the chloroform yielded a slightly yellow-colored oil from which solvent was removed under vacuum at 2 m m . The solid residue obtained was washed with 100 ml. of ether, filtered, and dried to give 6.55 g. of Ia as colorless crystals (yield Z r + )m , . p . 85". Anal. Calcd. for CsHloOiS (182.17j: C , S, l i . 5 6 . Found: C, 59.62; H , 5.76; S, 17.45. w-( Methylsulfinyl j-p-methoxyacetophenone ( I b ).-The solution of potassium t-butoxide was prepared as described for the preparation of Ta. T o this mixture (containing 51 Inmoles of potassium t-butoxide) 4.78 g. of methyl p-anisate (28.8 mmoles) was added. The reaction mixture as agitated by a stream of nitrogen for 4 hr. a t room temperature. Removal of the solvent as described in the preparations of Ia yielded a yellow mass which was shaken with 100 ml. of ether and 50 mi. of water a t room temperature. The yellow aqueous layer was covered with an additional 100 ml. of ether and acidified with a mixture of 6 ml. of concentrated hydrochloric acid and 24 ml. of water. Precipitated Ib, 220 mg., m.p. l o l o , was removed by filtration. Evaporation of the ether layer gave 670 mg. ( l
