2267
TAUTOMERISM IN UNSATURATED SULFOXIDES
June 5 , 1964
[CONTRIBUTIOX FROM THE PROCTER
& GAMBLE CO
MIAMIVALLEY LABORATORIES, CINCIXNATI 39,
OHIO]
The Relation of Proton Exchange to Tautomerism in Unsaturated Sulfoxides BY D. E. O'CONNOR A N D C. D. BROADDUS RECEIVED JANUARY 2, 1964 Deuterium exchange experiments with 1-rnethylsulfinyl-2-dodecene( I ) and 1-rnethylsulfinyl-1-dodecene (11) have shown t h a t I exchanges faster than 11. Both I and I1 exchange t o form the same deuterated Droduct 1 , l dideuterio-1-methylsulfinyl-2-dodecene. The proton exchange d a t a are s i n d a r to those obtained previously in studies with a,@-and 0,y-unsaturated isomers; however, the relative ground state stabilities of these P , y - and LY P-unsaturated isomers, I and 11, are reversed t o those of the previously studied systems. .In explanation is offered based on protonation of a common allylic intermediate more rapidly a t the point of higher electron density.
Introduction The role of carbanionic intermediates in base-catalyzed isomerization reactions is of high current interest.' ? %?thin this general area, a particular problem which has received very little attention recently concerns the nature of the factors governing base-catalyzed tautomerism in a,p-p,y-unsaturated system^.^ In the mid- 1930's Ives4 and Ingolds showed, by deuterium exchange studies, t h a t in certain systems p, y-unsaturated isomers underwent exchange rapidly compared to the a,P-isomers. Furthermore, the p, y-unsaturated compounds exchanged protons rapidly compared to their rate of isomerization. These results were discussed in terms of eq. 1 and required that kl > k z and k - l > kL-2.
-
H H R-C=C-CH2-X
ki
H H H
R-C-C-C-X + kL
k2
--+ k-
0
H H R-C=C-CHs-S-CH3
t
DO-I-Bu
+ KO-t-Bu -4
D H R-C=C-CD2-S-CD3 I11
n -
t
(3)
These results clearly show that the p,y-isomer is of lower ground state energy than the a,p-unsaturated compound, in contrast to the energetics of previously reported unsaturated systems of this t ~ p e . ~ The -'~ sulfoxide system, therefore, offered an opportunity to study the relation of proton exchange to tautomerism with isomers i n which the relative ground state stabilities were reversed to those previously reported
1
H H R-CHY-C=C-X
Results (1)
Since the thermodynamic equilibria in these syst.ems were similar, a generalization was developed based primarily on ground state energy difference^.^,^ Recent work8 in these laboratories has established that base-catalyzed equilibration of the unsaturated system shown in eq. 2 greatly favors the p,y-isomer I . Thus, treatment of the a,p-isorner I1 with potassium 0
Treatment of l-methyl~ulfinyl-2-dodecene~~ (I) with OD in DzO (0.9 31) for 64 hr. a t room temperature resulted in complete exchange of the doubly-activated methylene protons between the sulfoxide group and the double bond with no appearance of deuterium a t the y-position (eq. 4) lieither was there any evidence for n H H t CoHlpC=C-CH2-S-CHa
Dz0
+ on +
0
H H t CgHigC=C-CD2-S-CH3 I 17
t
H H CgHi gC=C-CH
gave exchange of the active hydrogens with no change in the relative amounts of a,@-and p,y-isomers (eq. 3 ) .
g-S-CH3
I 0 H H f CaHig-CH2-C=C-S-CHs I1
(2)
t-butoxide in t-butyl alcohol for 5 hr. produced a mixture consisting of 96% I and 4% 11. Treating this mixture with potassium t-butoxide in deuterated t-butyl alcohol (1) I). J C r a m and R . T. U y e d a , J . A m . Chrm S O L ,84, 4358 (1962). S B a n k , C A R o w e , Jr., a n d A. Schriesheim, i b i d , 8 6 , 2115 (196:3), a n d ref!-ences t h e r e i n , R B. Bates, R , H C a r n i g h a n , and C E. Staples, ibtd , 85,
3032 (1963) (21 W 0. H a a g and H . Pines, i b i d . , 84, 387 ( l 9 6 0 ) , I, Reggel, S . Friedm a n , a n d I . W e n d e r , J Org C h f m . , 28, 1136 (1938); F Asinger, B Fell, a n d G. Collin, ('hem. B f r . , 96, 716 (1963), IE. A Kabinovich, I V Astaf'ev. a n d A I S h a t e n s h t e i n , Zh Obshch K h i m , Sa, 748 (1962), a n d references therein ( 3 ) J H i n e , "Physical Organic Chemistry," 2nd E d . , McGran-Hill Book C o . , I n c . , New Y o r k , N . Y ,1Y62, p . 238 ( 4 ) I ) . J G. I v e s a n d H N R y d o n . J . Chpm Soc., 1733 (1935). ( 5 ) C . K Ingold, E. d e Salas, and C I..Wilson. ibid , 1328 (1936). (6) A . G . C a t c h p o l e , E . I ) . H u g h e s , a n d C . K Ingold, i b i d . , 11 (1948). ( 7 ) I n g o l d ' s rule s t a t e s "when a p r o t o n is supplied b y acids t o t h e mesomei-ic anion of weakly ionizing t a u t o m e r s of mat-kedly unequal s t a b i l i t y , t h e n t h e t a u t o m e r which is most quickly f o r m e d is t h e the,-modynamically least s t a b l e ; it is also t h e t a u t o m e r f t o m which t h e proton is lost most quickly t o bases" ( C . K Ingold, " S i - u c t u r e and hlechanism i n 08-ganic C h e m i s t r y , " Cornell University Press, I t h a c a , N. Ti.. I95:l, p . , 5 6 5 ) . ( 8 ) I). E O ' C o n n o r a n d W. I Lyness, J A m Chrm Soc., 86, :lo44 (1963)
(4)
the appearance of 1-methylsulfinyl-1-dodecene (11), as shown by the nuclear magnetic resonance (n.m,r.) spectra before and after deuteration. Thus the starting material gave rise to a multiplet centered a t 6.65 T (relative area 1.8) attributed to the doubly-activated methylene protons, as well as bands due to allylic protons a t 7.9 T (relative area 2.0), methylsulfinyl protons a t 7.t58 T (relative area 3.(1),vinyl protons centered a t and protons of the alkyl chain 4.3 T (relative area 1.8), (multiplet a t 8 . i T , relative area 14.4, and a multiplet a t 9.0-9.1 T , relative area 3.0).* The n.m.r. spectrum of the material recovered from the reaction was completely consistent with structure I V : the absorption a t 6.6.5 T had entirely disappeared and the vinyl proton multiplet a t 4.3 T had been somewhat simplified due to decoupling (9) G . A. R . K o n , R P. I i n s t e a d . a n d G W. G M a c l e n n a n . J Cht.m S o c . , 2434 ( 1 9 3 2 ) , R . P [ i n s t e a d a n d E G S o b l e , i b t r i 611 [!Wb4), A K a n d i a h and K P I.instead, ibid , 21:3$1 (1929). ( I O ) I ) . S Tarhell and W I;, I.ovett. J A m . C h r m . Sor , 78, 2259 (lOd6) (11) C . C Price and W H S n y d e r , J 0r.t C h e w . , 27, 4639 t I U R 2 1 , T r l r a hrdroii L e l l r i s , No. 2 , 69 (1962) (12) T J Prosier. J . A m Chrm. S o < , 83, 1701 (1961) (13) T h e mixture containing 9 6 7 ~i J f this compound a n d 4YC of I I was used in t h e exchange experiments
D. E. O’CONNOR AND C. D . BROADDUS
2268
QL
O C H z C N
m Fig. 1.-Energy
diagram for the interconversion of cyclohexenyl nitrile^.^^'
of the doubly activated methylene. The relative area of the vinyl proton absorption, however, had not decreased a t all indicating t h a t very little or no exchange had occurred a t the y-position. The other absorptions remained intact. Subjecting 1-methylsulfinyl-1-dodecene (11) to equivalent conditions (0.9 116 O D in DzO for GO hr. a t room temperature) caused a relatively slow exchange accompanied by tautomerism to 1-methylsulfinyl-1,lThe areas of dideuterio-2-dodecene (IV) (eq. 5). vinyl proton absorption of I and I1 in the n.rn.r. are 0 11
0
H H t C~H~~C-C-CDI-S-CH~ IV
(5)
sufficiently well separated that the percentage of each in a mixture of the two can be determined.8 The vinyl protons of I1 absorb a t 3.5-3.9 T , whereas the vinyl proton absorption of I is centered a t 4.4 and is entirely within the range 4.0to 3.8 r . By determining the relative areas a t 3.3-3.9 and 3.9-4,s r , it was found that of the starting material had been isomerized to the @, y-unsaturated isomer (accompanied by the appearance of deuterium in the aposition). The relative area of the allylic proton peak was practically unchanged, indicating t h a t very little, if any, deuterium had been incorporated into the yposition of the a,@-unsaturatedisomer. U’hen the reaction of I1 with D,O-OD- (0.9 ,If) was allowed to proceed for 2 weeks a t room temperature, 63% of I1 was converted to IV, the remaining 35Y0 being unreacteci 11. Thus, both I and I1 react to form the same deuterated product, IV, and under equivalent conditions I reacts much faster than 11.
Discussion of Results I t is apparent from a comparison of our data with that previouslv reported? that these systems give quite similar results despite the reversal in relative ground state stabilities. I n all these cases the ,B,y-unsaturated isomers undergo exchange rapidly compared to the
VOl. 86
a,@-unsaturatedcompounds. Exchange of the allylic protons without accompanying isomerization is observed with the @,y-unsaturated derivatives, while the a,@-unsaturatedcompounds isomerize during exchange. IVhile a mechanism based on a common allylic intermediate appears most attractive, concerted processes must also be considered. In the methylene-azomethine system, Ingold and co-uTorkers14l5 presented convincing evidence that tautomerism occurs by a concerted bimolecular process. These studies involved base-catalyzed tautomerism of optically active cornpounds wherein it was shown that a t short reaction times a completely racemic product was formed with no change in the optical activity of the recovered starting material. l6 Our studies with l-methylsulfinyl-2dodecene (eq. 4) show that a concerted process of this nature is not important in the present system. Thus, exchange occurs exclusively a t the doubly activated allylic position, whereas, if exchange were taking place through concerted formation of intermediate a,@-unsaturated isomer, incorporation of deuterium a t the yvinyl position in exchanged 1-methylsulfinyl-2-dodecene would be required (eq. 6). Intramolecular hydrogen transfer processes have recently been reported’ in
-OD
D 0
D H H f R-C=C-C-S-CHB D
(6)
reactions of this nature. Thus isomerizations have been observed in deuterated solvents in which no deuterium was incorporated in the isomerized material. However, we are obviously concerned here with reactions in which hydrogen exchange does occur. The intermediacy of a common allylic intermediate, i.e.. V, appears most reasonable in explaining our observations (eq. 7 ) . The exchange experiments with I
and I1 require that kl > k z and Ll > k-2. The similarity with the earlier data is striking. Since the relative ground state stabilities have been determined in these systems, their qualitative energy diagrams (Fig. 1 and 2) can be compared. As stated earlier, the data require that the relative activation energies in these systems remain the same while the ground state energies are reversed. From these observations i t must be concluded t h a t the differences in ground state energies cannot be the controlling factor in both cases. A more generally applicable explanation can be developed based on the relative rates of protonation of the x-system of these allylic anions a t the two positions of high electron (14) C K (1991).
Ingold a n d C
I,
Wilson, J . Chem. S O C , 149:( (193.3).
( l a ) S K H s u , C I(.I n g o l d , and C. I,. Wilson, i b i d . , 1778 (1935) (16) See ref 3 , pp 239-240, for a complete discussion of this work
4H
TAUTOMERISM I N UNSATURATED SULFOXIDES
June 5 , 1964
2269
density.I7 Both sets of data show t h a t protonation occurs more rapidly a t the carbon adjacent t o the 0
t
functional substituent (-CN and -S-CH3) than a t the carbon adjacent t o the alkyl group. In the allylic anions under consideration i t appears t h a t both the alkyl substituent and the inductively electron-withdrawing substituents should favor a relatively high electron density in the a-system at the a-carbon atom. Methyl-substituted allyl anions have been treated by Bowman and Hoijtink'* who suggest that donation of negative charge by the methyl group causes a lessening in the electrostatic interaction between a *-electron and the substituted carbon. This weaker interaction results in a relatively high electron density a t the unsubstituted position. Extension of this line of reasoning to an electron-withdrawing groupIQ leads t o the expectation t h a t in t h e *-system of the present allyl anions the higher charge density would be located at the position adjacent to the functional group. I t seems reasonable then t o ascribe the greater rate of protonation a t the a-position to its relatively high electron density. Once it is established t h a t k-l > k L 2 in both systems, the principle of microscopic reversibility demands that VI undergo deprotonation more rapidly than VIII, because AF-l < AF-2 and the ground state energy of VI > VI11 (Fig. I). However, the observation of the same order of reactivity in the sulfoxide case was not required. Thus, although AF-1 < AF-2 (Fig. 2), the ground state energies are 1 < 11. Since the same order is actually observed, it follows t h a t the activation energies required for protonation of the mesomeric anion V overshadow the energy differences of the ground state isomers (ca. 1.9 kcal.). In summary, then, it appears that proton exchange in all these a,p-p,y-unsaturated systems can be related to their tautomerism through a common allylic intermediate. Furthermore, the data reported to date can be rationalized on the basis of the allylic intermediate undergoing more rapid protonation a t the center of higher electron density regardless of the ground state stabilities of the tautomers involved. Experimental Preparation of 1-Methylsulfinyl-2-dodecene (I).-Reaction of 147 g. (0.9 mole) of dodecene 1-oxide with 39 g. (0.8 mole) of methyl mercaptan in 500 ml. of ethanol containing 45 g. (0.8 mole) of potassium hydroxide a t room temperature for 2 hr. gave l-methyIthio-2-hydroxydodecane, which was oxidized with 100 g . ( ( a . 0.88 mole) of hydrogen peroxide ( 3 0 % ) a t room temperature for 6 hr. to yield 148 g . ( i 5 5 ) of 1-methylsulfinyl-2-hydroxydodecane, m.p. 69-71 O (mixture of diastereoisomers). To a solution of 0.07 mole of potassium t-butoxide in 100 ml. of t-butyl alcohol was added 12.4 g. (0.05 mole) of l-methylsulfinyl2-hydroxydodecane. The mixture was heated a t 60" for 4 hr. (17) M a n y a u t h o r s have suggested t h a t relative rates of protonation in resonating systems are directly dependent upon t h e a m o u n t of negative Among these a r e : R G . Pearson charge borne by t h e atoms in question and R . IXllon. J A m . Chem. Soc., 1 6 , 2439 (1953); G. S. H a m m o n d , i b i d , 77, 334 ( 1 9 R 5 , G Russell, ibid., 81, 2017 (1959), A J Birch, Q u a ~ fRev. . (London), 4, 69 (1950); H . E Z i m m e r m a n , "Molecular Rearrangements," edited by P . d e M a y o , Interscience Publishers, I n c . , S e w York, N Y , 1963, p . 346, A. Streitwieser, J r , "Molecular Orbital Theory for Organic Chemists," John Wiley and Sons, I n c . , New York, N . Y . , 1961, P. 418; ref. 3 and 1 8 . ( 1 8 ) S . Bowman and G. J . Hoijtink, Rec. fra8. chim., 16, 841 (1957). (19) See I> A . Brown and M . J S Dewar, J . Chem. Soc., 2406 (19531, for a discussion of electron-withdrawing groups causing inductoelectromeric effects in heterocyclic systems.
AF-
1 :HS
*
0 H H R-~=~-cH~-s-cH~
I Fig. 2.-Energy
R - c H ~ -W c = c -O& - c H ~
II diagrams for the interconversioii of I and I1
and was then cooled and poured into 300 ml. of water. The product was extracted three times with ethyl acetate, the extracts were dried over magnesium sulfate, and the solvent was evaporated. The residue was taken up in hexane and cooled. X precipitate of 1.0 g. of starting material was obtained. The 10 g. of liquid residue remaining in the supernatant liquid was distilled t o yield 8.1 g. of crude product. Redistillation of 5.0 g. of the crude product gave 2.1 g. (29%) of I-methylsulfinyl-2-dodecene, b.p. 131' (0.2 m m . ) . ilnal. Calcd. for C L ~ H ? ~ OCS, : 67.8; H , 11.37; S, 13.9. Found: C, 67.6; H, 11.2; S, 13.6. An infrared spectrum had bands a t 9.5 IJ (s) (sulfoxide group) and 10.3 ( m ) (trans double bond). An n.m.r. spectrum (1.arian .%-BO spectrometer) determined on a 10'; solution in carbon tetrachloride had absorptions due to olefinic protons (multiplet centered at 4.4 T , rel. area 1.8), methylene protons between the double bond and the sulfinyl group (6.65 T , re]. area 1.8),methylsulfinyl protons (7.58 T , rel. area 3.0), allylic protons (7.9 T , rel. area 2.0), alkyl methylene protons (8.7 7 , rel. area 14;4), and terminal methyl protons (9.1 T , rel. area 3.0). The n.m.r. data were given previously and it was shown t h a t 4% I1 was present in the sample of 1 . 8 Preparation of 1-Methylsulfinyl-1-dodecene (II).-A 300-ml. autoclave was charged with 66.4 g. (0.40 mole) of 1-dodecyne, 14.4 g. (0.30 mole) of methyl mercaptan, and 1 g. of azobisisobutyronitrile ( A B N ) . The autoclave was pressured to 500 p.s.i. with nitrogen and was heated a t 65' for 4 hr. I t was then cooled and vented overnight after which the products were removed atid distilled through a Claisen head. Fractionation through a 2 1 in., 8 m m . diameter, spinning band column yielded 41.2 g . (64
