Vol. 35, NO'.

S, March 1970

USE OF LITHIUM REAGEN'rs IN KETONE SYNTHESIS

777

The Application of Lithium Reagents from

(l-lUethylthio)alkylphosphonate Esters to the Synthesis of Ketones
Eo J.

COREY AND .JOEL

I.

SHULMAN

Department of Chemi8try, Harvard Univer8ity, Cambridge, Massachusett8

02138

Received July 15, 196,9

Diethyl methylthiomethylphosphonate can be alkylated by suc('essive treatment with n-butyllithium and
an n-alkyl iodide to give the corresponding (l-methylthio)alkylphosphonate esters (4). The lithio derivatives
of the latter (5) react with earbonyl compounds to form t/-alkoxy phosphonate adducts, which decompose upon
heatillg to 50 (in tetrahydrofulItII) to form substit.uted vinyl methyl sulfides (7). Ketones are obtained in good
yield by mercury(II )-promoted hydrolysis of the vinyl sulfides 7.

Pho:iphonate esters containing an electron-with

drawil:g substituent (la-d) form stabilized carbanions
which can effect the synthesis of certain olefins from
aldehydes and ketoncs. 1 2 Very recently,3 the scope
of thi" reaction has beell extended to include the syn
thesis of a,{::-unsaturated sulfones via the phosphonate
ester Ie. It has also been shown 4 that the unstabilized
narbanions from If and 19 can be formed as lithio

OR

XCH:P(OR)2

o
/I

la, X = COR'

"

II

(C6H 5 :'.C-,HP(OR}2
X

e, X = S02Et

o
h, X =CR'

f, X-H

c, X-CN

g, X= CH 3

d, X = Ar

h, X=SCHJ

"

2a, X-H
h, X-CR3

derivatives and that these aniuns react with carbonyl

compounds to produce i3-hydroxy phosphonates, e.g.,
the adducts 2a and 2b from benzophenone. However,
evell in cases most favorable for olefin formation such
as 2a and 2b, Wittig elimination does not occur satis
factorily either from the iJ-hydroxy phospho nates or
their conjugate bases. It was concluded 4 that the
facile Wittig elimination of the {3-alkoxy phosphonates
requires the presence of an electron-withdrawing
substituent on the carbon a to the phosphorus func
tion.
The ability of bivalent sulfur to stabilize an adjacent
carbanion5 sugge"ts the use of the thioalkyl moiety as
all activating group X ill the phosphonate olefin
~ynthcsis; the product of such a reaction would be a
vinyl sulfide, a convenif'nt precursor to aldehydes or
ketoJle::; through hydrolysis. s Indeed, Green 7 has
achicn,d limited success with a vinyl Allfide synthesis
(I) (a) W. S. Wnd''''orth, Jr. and W. D. Emmons. J. Amer. Chern..
Soc., 83, 173:> (1961); (bJ 1.. Hurner, II. Hoffmann, and H. G. Wippel.
Chern. BPI. ,91, 6:1 (1958).
(2) For a recent review see A. V. DombrovBkii and V. A. Dombrovskii.
/{u,s. Cltem. 1In'., 35, i.i3 (1966).
\3) 1. C. Popof', J. L. Dever, and G. R. Leader, J. Oro. Chern., U, 1128

(1969).

(4) b. J. Core)' and G.T. Kwiatkowski, J. A mer. Chern. Soc., 88, 5654
(Wuo).
(5) G. Cilento. Chern. Rev., 60, 147 (1960).
(6) Ca) B. S. hupin and .\. A. Petrov, Zh. Oro. Khim . I, 975 (1967);
(b) J. II. S. Weilund and J. F. Arens. Rec. Trav. Chim. PaY8Bas, 79, 1293
i1~GO); (c) T. M ..kaiyama, S. Fukuyama. and T. Kumamoto, Tetrahedron

Lett., 3787 (1968).

using Ih as substrate, but his reaction conditions

severely "limit the value of this reaction as a synthetic
method." 7 We report herein the ready adaptation of
the phosphonate olefin synthesis to the preparation of
vinyl sulfides, and the subsequent hydrolysis of these
compounds to unsymmetrical ketones.
We found that diethyl methylthiomethylphospho
nate (3)1 was metalated readily by 1 equiv of u
butyllithium in tetrahydrofuran at -70. The alkyla
tion of the lithio derivative was a facile reaction, af
fording good yields of diethyl (l-meth:r lthio) ethyl
phosphonatc (4a) or dietilyl (l-methylthio)nonyl
phosphonate (4b).
Sequential treatment of the
phosphonates 4 with n-butyllithium and an aldehyde
or ketone gave adducts 6, which upon heating at 50 0
eliminated diethyl phosphate monoanion to give vinyl
sulfides 7. The lithio derivatives S could be formed
either at -70 0 in tetmhydrofuran or at 0 iII cyclo
hexane. The intermediacy of the hydroxyphosphonate
anion 6 was demonstrated by the aqueous quel1ching of
the rraction mixture from Sa and benzaldehyde, where
upon protonated 6a was obtained in 88% yield.

II

CH3SCH2P(OEt)2

Li

I I

o
CH3SCHP(OEt}l

"

nBuLi

R
4a, It-CH,
b, R,.. CHiCH 2);
Li
0
CF P '

I I "(OEt)!

R,R,C-O.

CHasr-P(OEt)2

RIR2C-C"

SCH,
6a, R - CH' Rl = CJIs;

Sa, R-CH 3
b, R - CHaCCH2),

"It
R,RzC=C,
SCH3
7a, R - CHa; Rl - CJIs; Rz - H
b, R-CH.; Rl = CH,(CH2),; R2 - H

(EtO)2POO'-Li +

The scope ;~f the ~ynthesis of vinyl sulfides via the

Emmons-HoT'rier pliosphonate' reaction can be seen
from the data in Table I. In the two instances which
afforded low yields of vinyl sulfides (i.e., cyclopentanone
and acetophenone), substantial amounts of base
catalyzed condensation products were obtained, in
dicating that for these ketones enolate formation by

..'j
,

778

The Journal of Organic Chemistry

COREY AND 8HULMAN

TABLE

CONVEHSION l{, H,Ccf)

-- ItdhC=Clt(8ClI a)

USING DIETHYI, (l-l\l~:THYLTI/IO ).\LKYLPHUi:'I'HON ATl:S

Carhonyl eompd

Solvent a

Yield
uf vinyl
sulfide,b %

C fI3
CH,
CH,
CH,

Benzaldehyde
T
80C
Benzuphcnollc
T
84
Rexanal
T
67 d
IIexan:l1
C
67
cn,
Cyclohexanone
T
82
Cyciohexnnone
T
72
ClII,(CR l h
G:l 3
Acetophenone
T
Trace"!
cn,
Acetupheuone
C
Trace'
CIl,
Cyclopelltanone
T
7-10"
'; II,
Cyclopen tanone
C
7-10
a Solvents:
T, tetmhydrofurall; C, cyclohexnne. b After
purifieatiop hy preparative tIc. 'Major iHomer, E. S:Y/c,; minor
isnmer, Z, 17'1i. d\Iajor i~omer, E, 60';;; mill"!' i~()lIler, Z,
MY/o. 'Isumer ratio nut determil,ed. ! A mixture of IIcetophe
I"Hle and its ba,.;e-cataly;~ed condell~ali(Jn product (a-methyl--i3
benzoylstyrcne) was recovered in ca. 60% yield. .2-Cyclo
pentylidene cyclupentallone was abo isolah:d in 3;,)'1(, yield.

Such behavior is especially characteristic of cyclo

pentnnone in Wittig-lype r'.~action::;.8
In those in"tances where the formation of isomeric
vinyl sulfiJe::; was po,;..,ible (7a alld 7b), the isomer
ratios as given in Table I were determined by vpc.
Stereochemistry was assigned from mnl' data; in
partim: lar, the chemical <;hifL: of the vinylic protons were
diagnostic. Use of the tables of Pascual, :\Ieier, and
Simon,9 which correlate chemical shifts of olefinic
protons with their chemical environments, indicates
that the vinylic proton in 7a-EIO will appear at {) 6.10,
while the spectrum of 7a-ZIO wir have this proton at {)
C6Hs'C=C/SCHl
H/
'CH3
7a-Z

7b-Z

/CH
C=c'SCll
3

II""

7a-E

CH,(CH2k,c=c/SCHJ
H/

CGH",

'elI,

CH 3(CH 2).,
CH,
H;::C=C;'C;I 3
7bE

0.:3:l. In fact, the nmr of 7a revl'aled broad singlets

a' {) '0.12 and 6.40, with the former predollJinating
(::\: 1 ratio). The major isomer is thu" as::;igneJ the E
stereochemistry. Likewi::;e, the chemical shifts of the
vinyl protons of 7b-E and 7b-Z are predicted to be {)
!'i. H) and 5.42, respectively. In fact, these protons
appeared as hroad Lriplets at. {) 5.17 and 5.45 in a 3:2
ratio. The major isomrr is therefore again assigned the
E stereochemistry.
The hydrolysis of villyl sulfides to ketones (or alde
hydes) has usually been effected under rather drastic
acidic conditions. 6 Srcking a mildcr hydrolysis pro
cedure, wc investigated the use of mercuric chloride
(8) D. R. CUllIson [Tetrahedron Dell . 3:123 (Hl64) 1 found only 2-cyclo
pentylidrme cyclopentanone (!}O',;;, yield) upon reA.e1ion of cyclopentan,)oe
with (C,.II,hP=C(CH.)OC II.. G. Wittig, W. Roll, and K_-H. KrUck
[Chern. fJ'er, 911, 2514 (19fl:!I] could iKolute the de.ired vinyl ether from the
reacti(Jll of cyciopentnnonc ..dth (C,dh),P=-,-CHOCII. in only 14(;;) yield;
a large amount of aldol conden.::lstion product was alsu formed.
(9) C. PnBcual, J. Meier. and W. I'imon, lIelv. Chim. ;I"',,. n. 1M (lY6G).
om 8'le J. E. Black'yo'HI, C. L. G1uri),", K. L. Loening, A. E. Petrarca.
and J. E. Rll~h, J. Amer. Chern. 8()c., 90, ,t;OO (1\)68), for the use of the
Entgp.l[en-ZU8amrnen priority llOmmwlatllrt) t.o IIIpecify (':onfif,Ctlrll.t.ion ahout a.

uouhle twnd.

in aqueous acetonitrile II and found that this medium

afforded high yields of the pure ketones. Table ~I
shows the results of these hydrolyses. To ubtam
optimum yields, the reaction mixtures were worked up
soon after the disappearance of the vinyl sulHd(~s (a8
determined by tic). This avoided aldol condensation
of the ketones, catalyzed by the acid formed along with
the insoluble mercury mercaptide.
TABLE

II

IlYDHOLYSIS OF VINYL ~ULFIDES '1'0 K~;TONER

H,R,C=CH(SCH,)

HI

R,
H
C-lLI.

H,H,CIICOH
Temp,

Yield of

C (hr)a

ket,one,b %

50 (~) 1)
ClI 3
C,Ils
CIl 3
C,II.
S2 (41 j
25 (2())
CII,
(CII,)o
CII,
CII,\ ('If,),
H
25 (6)
CII,(CI-Lh
(ClI,).
40 (26)
a Aqueous acetonit rile. 2 eqlliv of nlPrcllric ,hloridc.
purification by short-path distillatioll. 'Purified by
chrumatography.

84
86
78
14'
92
b After
colum ll

The success of the yinyl sulfide formation and sub

sequent hydrolysis provides a cOIlvc:Jient, efficient
synthe::;is of l;:ptonc" of the type neOH', where L
originates from :tn alkylating agent and H' embodies
the carbon skeleton of a ketone or aldehyde. The
utility of the ::;ynthesis is best secll in the ca;e of e:'clo
hexyl n-octyl ketone, derived from II-oct.yl iodide and
cyclohexanolie. This ketone has been prepare,l by' (a)
the glycidic ester synthesis l2 (overall yield, Cfl. l.i%),
and (b) the hydrobomtion of l-octene wit h dicyclo
hexylborane and suhsequent carbonyl:tt iun and oxid:t
tion13 (overall yield 71%, but contaminated with 1!J%
dicyclohexyl ketone). In compari~on, the prc"cnt
synthesi::; affords eyclohexyl n-octyl l:ciolle of high
purity in good overall yield (tj(j%, two step.s, purified
intermediate).
Experimental Section
Melting points were taken ill glass capillary tubes with 3
Bllchi apparatus allli n t' correeted; boiling points are LIn'
purredI'd. lnfrurcli spectra WI'fl' recorded for II< d.liqllid sample,;
with a Perkin-Elmer l\lode! 1:37 ~pe('(roph(jt"I1"!"r. lI.';illf( the
6.24-~ band of pulystyrene Lt." ~tallliard. Hefr:H't ivc indic('s were
obtained using It Blllisch and Lomb Abbe.:;L refractometer.
Nudear magnetic resonance dat.a were determined for soluI ions
in CnCIa (unless otherwise specified) at 60 1\1cp using V:ifilln
Associates Model A-60 or T-60 instruments and are cxprpsseJ
ill parts per millinn (ppm) duwnfield from internal tetramethyl
silane. Tet.rahydrofuran (THF) was dried before use by di,;(illa
tion from lithium fLhlmilllllll hydride. Analytienl g:" ,hro
matogruphy was perforllled Oil the following columns: 6 ft X
0.12:, in . .'i% Carbowax 20M Oil (;as-Chrulll Q, F & :\1 :\lodd ~iO
or 1i7!iO instrument with flame ionization detection ('ollln'," A);
10 ft X 0.25 in. 5(;;0 SE-aO silicon rubber on Ointoport H. F' & :\1
l\Iodel 300 instrument with thermal eOll(lite( ivity dn1Pf'! ion
(column B); to f1 X 0.:2;-, in. fi";! QF-l fhlOrosili('J)lIlll' l>iat,ojlurt
S, F & l\I Model aoo (column C). Flow rates were, for cp'lllllll
A, an ml/min; for colulllns B ami C, (1) ml/min. Elemclltal
analyses were carried out by Scandinavian :\1 iCl'oanahti":11
Laboratory. Herlev, I )cnmark. and by Elek :\Iicro:lnalytica!
LaiJOratory, Torrance, Calif.
(11) See Eo J. Corey and D. CrrHl"e. J. Ory. Chern .. 33, 298 (1!>68), for
tlJe U8e of this system for the hydrulysis of dithjanc~,
(12) II. II. Morris und 1\1. L. Lllsth, J. Amer. ('hem. Soc., 76,12:17 (W;'4).
These authors also prepafP<i :-lome of the kl'tonC' fur comt,ari~oll by an alkyl
cadmium-type (iri~lU\rd relll'lion. Nu yhld '\Ili'l: I{h'(>n,
O:l) II. C. Brown "I1<IM. W. Il"thk,', ;I,;d., 89, 4r.2!l (11107>; II. C. Brown.
G. W. Kabalka, and M. W. Hathke, ibid., 89, 45:lO (11167).

Fol. 86, No.3, March 1970

Diethyl (lMethylthio )ethylphosphonate (4a).-A solution of
g (GO mmol) of diethyl methyithiomethylphosphonate7
ill :WO Illi of ury Till<' under argon anu ('oled to _70 was
trcated with iii ml (62 mmol) of 1.22 III n-but,ylIithiuIll in
pentane. t'ti ITing of the yellow solutioll was continucd for.') hr
III -70, after which time 4,4 ml (lO.1) g, 70 mIllol) of methyl
iodide was added. After an additional ;)() min at -70, the solu
tion W!l~ allowed t(, warm to room ten,perature. The bulk of
the solvents were removed Oil a rotary evaporator, and the
rernailling yellow oil W:iS treated with 7:; 1111 of water and ex
tracted with two 7ii-ml portioll'; of etiIer. The eombinrd extracts
Wl'n~ wa,hul wilh brine, dried over anhydrous magnpsiulll blIifate,
and (list illed. Thrre fnwtions were c.ollected, total 9.7ii g (77'7<J,
at ll'mpemtures of ;i;i-70 (0.2() mm); all were shown by nmr
10 [,C sutlieiently pure for further use. ~,[ost of the product hoiled
at 6:-;-70 (0.:,:0 mm): purity >!Jii({ by vpc (column A at 150,
retention time '2.7 min); n23[) J Afl'2(); nmr () 1.3ii (triplet, 6 II,
J/JlI = 7 ('j)~, methyl groups un the ethyl e~ter), 1.4,,; (doublet.
of doubl!,!:;, :3 H, Jllll = 7 cps, Jl'lI = 16 ('Jl~, methyl adjacent
to phtl~phoru:,), '2.'2!) (singlet, :l H, methyithio), 2.70 (~Yll1metrical mul'iplel, 1 II, mcthine), nnd 4.'20 !symrnetrieal
multiplet,4 JI, methylene on ethyl ester). The infrarcd :;Jlcctrum
was eharaderizcd by a stroll!!: 1'=0 stretching ahsorptiqn at 8.00
po ami a CII.OP strelclling vibration at i'.ii.'1 p..
Anal. Caled for C7 J[ 17 Pi:i0 3 : C, ;{!).60; If, S.OS; f-I, 14.GO.
FuulId: C, ;l~.IA4; II, lUll; f', 11.6i.
Diethyl Il-;lIethylthio :Il(Jnylphosphonate 14b).--T,\ a .-<"Jlllion
of II.S" g (1"1 lllIllol) of di"Il!\'1 1l11't1,,lthi(\llll'thylph""1'IhHl'lte7
ill '20() IlII uf C,IY TllF under aq,(lll ami at _iflo was add.'d :ii
ml ((j7,ll!llltll) of 1.'2'2 J[ n-lJulyllilllilllll in pell\lllJP. Aiter 4 hI' uf
stirring, the solutioll wa,.; treatcd with IS.(I g 17.-, !l1l11,,1) of n
uetyl iodid,', "e"ulting ill thp iormati,,'l of II jli'cclpi(;,'l'. The
III ixt Ilre \V!h ~t iI'\( ,d [l t - 70 0 for 4;; mill, t IH'II :It room I ell, per:L! IIrc
fur ].j Ill'. Hemoval of the bllik of the s()ivCllh "j:h " ro:a~''y
eVajHJr:ltor and work-lip as ahov(' afToJ'(.Ied, after di-;tillatioll,
G,4t; g, bp 12:::-.1;)'2 (I).l2 mIll), alld (iA2 g, bp l:l~_I:::lo (0.12
mill). That. the"e fractions w('!'e identical wa, shown bv nmr.
The tolal yilld was l'2.S() g :U!)'.';,): n"!/) 1.4620; lln,,' li (l.S9
ICllJlapsC'd triplet,;-I II, tC'rmilillsof alk}l ('hain), 1.1-'2.0ille\udillg
j .:)4 (t riplet, .1 11/1 = 7 cps) alld a brnad envelope peakillg at 1.2S
('20 II. methyl groups on ethyl estels, a.nd methylene prot.ons on
!llkyl chain), :~.l:-: (singlet, 3 H. methylthio), 2.60 (broad mul
tiplet, 1 II, lIIcthinel. and 4.20 (symmrtrical multiplet, 4 II,
lll('thylene~ on ethyl esters). The infrared spectrum contained a
,:tl'l1llg 1'=0 stretching band at 1'.00 p. and a CII,OP slI'etching
vibmtil)!1 at R.60 po.
Anal. Caled for C\,H 31 PS0 3 : C, .')4.17; H, 10.07; H. 10.33.
Found: C,54.41; 11,10.00; S,10.2S.
Preparation of Diethyl (l-Methyl-l-methylthio-2-hydroxy-2
phenyltethylpllOsphonate (Protonated 6a) from Diethyl (1
Methylthio )ethylphosphonate and Benzaldehyde .-'1'0 a solution
0;' 212 fIlg (1.0 mmol) of diethy! (l-methylthio)ethylphosphonute
ill I {) illl of dry TIlt' under argon and at -70 was added O.S:i ml
1,1.1. mmol) uf 1.:3 J! n-butylliihium in pentane. After :1.7ii hI'
tIll' ~()Iution wa~ treated with 1.0 ml (l.Oii g, JO.O Illlllol) of
bcm:tldehyde. Follnwill~ stilTing at -70 alld (]O for 1.". min each,
Ihe ",actiolllllixtlll'e was poured into 10 ml of water and extmcted
with j() ml of ethel'. The extrad waR washed with ~ueces~ive
)()-llli port.ions of saturated iHIUh'U:; :lInmonium chloride, sudium
bi('arhonate, and sodium chloride. Evacuation at 1 Idll for
17 hI' Inrt 2:-;0 mg (i'.'i';;) of the hydroxyphosphonate. The nml'
"pc('tnlIll showed peaks at [; 1.'20 (('omplex envelope, \J II,
Illethyl grollps Oil ethyl csters alJ(1 adjCl('(,"t to phosphorus), J.90
and '2.'20 (~illglets, 3]f, methylthio in Ihreo and erylhro isomers),
4.20 (multiplet., 4 If, methylene protons on dhyl esters), 4.;')6
(singlet, I II, hydroxyl), ;i.U!J and ;i.IS (pair of duublets, 1 H,
J I'll = II awi G cps, methine, threo and erythro), and 7.41
(multiplet, :, II, aromatic).
General Pro,~edure for the Formation of Vinyl Sulfides.-To
:11 () mg (2 A mTllol) of diethyl (1-methylthio )e( hylphosph<JJlate or
744, IIlg (2.'1 mlllol) of diethyl (l-methylthio)nonylphosphonate
ill 12 ml of dry 'I'HF at -70 or cyclohexane at 0 and under
argoll was ~l'ldetl 1.6 ml (2.0 mmol) of J .'2;') M Ii-butyllil hium in
]lelltane. The resulting solutio]} was stirred at low tcmperat.ure
( --7t) ur 0, dl~pending ujJon the solvell t) for 4 -(i Ill. The car
"()]!yl cOlnpound (1 ..'1 mrnol) W!lS added, neat or in 4 ml of THI<'
"I' eydoh"xane, and st irriag was cont.inued at low temperature
for ;j()(i(J min. The clear sulution was next hellted at. 50 under
:',,,IJll for 15-2') hI' to effect elimination of the diethyl phosphute
alllon.
11.S.'-;

USE OF LITHIUM HEAm;NTS IN KETONE SYNTHESIS

779

The result ing mixture, now yellow (varit)u:; intensities (If brown
for reartions that gave poor yield, of vinyl sllifides), was treated
with 10 ml of water and 10 ml of ::;aturated aqueous ammonium
chloride, and th'" extracted with 10 ml of ether. The ether
extract WitS slH'cessively washed with IO-ml portiO/IS of sl1turated
aqueous sodium bicarbonate and brine; all I1queous phases were
backwashed with 10 ml of ether. The combined ether extracts
were dried over anhydrous mltgnesinm sulfate and conceil trated
on a rotary evaporator. Isolation of the pure vinyl sulfide was
readily accomplished by preparative tl ... on silica gel PF,,,, using
1: 1 methylene chloridecyeJohexane a, eluent. The vinyl
sulfides were all active in the \lV, with HI values uf ca. 0.7.
Methyl a-methylstyryl sulfide (7a) was ubtaiJwd in 80% yield
by the addition of neat benzald(\vde to the anion Sa, formed in
TIIF. Vpe (column A, 100) showed the liquid pruduct to be
h()mogelleou~. The two possible isomers (7a-E, retention time
ii.:l min; 7a-Z, retention time 6.:l min) were prescI,t i" a fi:l
ratio: IImr [; 2.0() and 2.1J (dollblets, J II, J = 1.ii cps, E and
Z vinyJic met.hyl groups, respectively), 2.20 ami 2.26 (singlets.
3 II, Z alld E methylthio groups, respeetively), 6.12 and G.40
(hroad singlets, 1 IT, E and Z vinylic prot.olls, resp('ct ively), and
7.20 (hroad silll;let, ii II, aromatic). The infrared spet:tmm COB
tained bands at 6.20 and (l.:iS po, owing to a double bond con
jugated with an aromatic ring. Both infrared and Ilmr spectr"
were virt.ually idenUt',,1 with th')se rf'ported 6n for the vili:'-! >:ltI
fide. The Hussian workers rile! not report Ilw i:conwl' l':t'in of
their vinyl :'ldfide (folilwd h,: thc n,:lI'tilili of (\,Ti,C"o(:{ 'lf, wit'
CIl:.Sll.< !>Ill tl", miio "f th'" "l"fillir 1'1',;1,., in' ',,).. II [,f (f"'ir
prodlH't ~et'Il!(l.d t.u he llt;';Uq: 1hc' :-~lll.li.! d,S i;; i!lf' iJ1P~,t.tii (':~ !
The prodllct. l.;td n 24 lJ 1.li{).'{j (iii ."1< /I'''" I.Gi'2.-, \.
Me ';\yl I-methYI-l-heptenyl sulfide (ilJ) W'l!; Pl'lV'Uf'rl iCi n;'Si
yip1d hy tht~ ,.. {hlil..ij'd of LC,\HIl:Li (IH~[ji ;)J' in SldlltlOll i i \ ihe hiiioll
5.1, fOl'lllPd i, eithpr TIIF or ('yd, "in,,,,,,,
V)l(' (,'<I'lll'lL A
100) sh()\\;~d the oil 1() \,(. h"rn"~l'llCI)\h ,Il.d II ;,'::: mi,j 'II" ot E
and 'h i~()jner~ (rctt.IJiioll t-inle~ 2.1 (llld I.S :tlill, fC;o.]w('tJvelyi_
The 11m]' speetrUlll ('o!ltnilled peak" !It {) O.::!l (follllp~ed tnpi('\,
:l II, methyl at termillu" of alkyl chllin), J.;)O (multiplet, (j 1[,
methylenes), 1.'-1,7 lind I.B!) (doublet",;; II, J = ca. I.ii 'VS.
vinylie methyls 011 E ami Z isonlPl's. respect.iv<.-iy), 2.J-2.:j
(multiplet,:2 II, IllJylic prutolls), 2.20 (siuglet, a II, methylthiu),
and 5.17 and 5.4.') Ihl'l1ad triplets, 1 H, vinyl Pl'OtollH of E and Z
isomers, respectively). 'fpe infraled spectrum showed a C=c=C
st ret.ehing frequency at 6.14 p..
Anal. Calet! for C.If"S: C, GS.2k; II, 11.46; S, 20.'2(;.
Found: C, G'i.:!O; H, 11.4.'); S,20.22.
Methyl a-methyl-/3-phenylstyryl sulfide was prepared in >14';>(,
yield by t.he Itddition of a THF soiLltlUn of benwphenone to the
anion Sa in TH F. The product, a vaguely yellow wlid. mp
3fl-;{SO, was homogeneous hy vpe (column Bat H)O, re(pntion
time ii.S min): nIllr {) 2.10 (,inglet,;j II), 2.IG (singlet, :l H), and
7.~O (multiplet, 10 Il). The infrared t;pectrum di::;played C=~~C
st.retehing vibrations I1t 6.2R and 6.;)!) /J.
Anal. Caled fur C'6H'6S: C, 7!J.04; H, 6.71; S, 1;{.34.
Found: C,7!l.!J4; II,6.Gl; S,I;).:2;{.
Methyl (l-cyclohexylidene )ethyl sulfide was obtained ill S2%
yield by the addition of a :,,,Iutioll of fleshly disi illrd 14 cye\o
hex!luone in TIll<' to the anion Sa, formed in TIfF. The oily
prociu('t was shown to be homogeneous by vp(' (culumn C at
100, retention l.ime 6.6 min): nIll!" [; 1.4ii (multiplet., 6 If,
alieyclie), l.U:-; (Hinglet), 2.19 (single!.), Illai 2.0-'2 ..') (multiplet,
10 1I, villylk llll'thyl, methylthio, and allylic protons, respec
tively). The infrared ~pe('truTll cuntaincd a weak C~cC strNch
illg absorption at 6.16 IJ..
A.nal. Calcd for C uH 18S: C, 69.16; IT, J().ci'2; S. 20.5'2.
Found: C,6S.()4; II,10.24; S,2fl.()6.
Methyl (l-cyclohexylidene )nonyl sulfide was prepared in
72% yield by the addition of a solution of freshly distilled eyclo
hpxanone in Till<' to the anion Sb, abo in TIlF. Vpc (e. ;,lllln II
at I!JO, retl'lltiull time 6.'2 min) proved the homoglClJeity uf the
oil: nmr 0 O.S!J (poorly resolved triplet, :; If, terminal methyl
on the alkyl chain), 1.:30 (broad band. 12 II, aliphatic methylelles),
1.53 (broad singlet, 6 II, alicyclic methylcnes), 2.13 (sharp
singlet, a II, met.hylthio), and 2.0-2.7 (multiplet, 6 H, allylic).
The infrared spectrum ('ontained a weak C=C 51 ret ching fre
qllen('y at 6.1.'-; po.

(1-1) It was obHefvcd that the use of cyclohexauone which had Leon
distilled and stured under nitro~en in a 8f>rUm-Htoppercd fl{u~k for 5 days
gave drastically reduced yields of vinyl sulfide.

780

Tile Journal of Organic Chemistry

COFtEY AND SHULMAN

Anal. Calcd for ClsHaoS: C, 7:.:t; H, 1U\8; ~, 12.60.

li"(mnd: C., 7.5.77; H,l1.86; S, 12.44.
Reaction of the Anion Sa with Cyc1opentanone.-When the
general procedure for the formation of vinyl sulfides was carried
out, adding a solution of freshly distilled cyclopentanone in
THF or cyclohexane to the anion ;,a ill the same solvent, only
7-10% of the desired methyl (l-cyclopentylidene)ethyl sulfide
could be j"jlated. H0111ugeneity of the product was proven by
vpc (column B at 100, retention time 4 ..) min): nmr Il 1.69
(multiplet, 4 II, alicyclic), 1.96 (triplet,lO 3 H, J = 1..5 cps,
allylic methyl), 2.2;' (singlet), and 2.1-2.6 (multiplet, 7 II,
methylthio anll fillylic methylenes). The infrared spectrum
contained Il, weak C=C stretching ahsorption at 6.10 p.
Anal. Calcd for C,H 14S: C, 67.53; H, 9.92; S, 22 ..')4.
Found: C.' 07.59; H,9.S:;; S,21.90.
In addition, a 35% yield of 2-cye1opentyli(i<-ne cyclopentanone
was isolated by preparative tIc (U, 0.40, silica gel, 1: 1 methylene
chloride-cyclohexane). The nmr spectrum contained only II
complex envelope of peaks at Ii 1.3-3.0. The infrared spectrum
contained strong bfinds at 5.R2 and 6.UJ p.16
Reaction of the Anion Sa with Acetophenone.--The general
vinyl sulfide procedure was carried out with Sa and aeetophenone
in either THF or cyclohexane; only 3 mg ('" 1 c!C') of material with
the correct R, value fot" a vinyl sulfide (0.75) could be isdated;
this materi:~l was not further chanccterized. In addition, a 60%
yield of a mixture of acetophenone and it~ aldol condensation
product WllS recovered. The condensatiun product had an nmr
spectrum containing a villylic methyl at & 2.17 and an olefinic
proton at Ii 6.IIl, in addithjll hl aromatic protons.
Phenylacetone.--To a solutiOlI of 90 mg (0.i,)5 mmol) "f methyl
a-methylstyryl sufide in 4 ml of 3: 1 acetonitrile--water was
added a solution of 30() mg (1.1 mmol) uf mercuric chloride in 4
ml of the same solvent Rystem. The cloudy mixture was stirred
at :;0 for 21 hr and then filtered through Hyflo Super Cel, with
thorough ether washing. The filtrate was washed with aqueous
sodium L!l(:llrbonllte and then with brine and dried over anhy
drous magnesium sulfate. Concentration on the robry evapora
tor and short-path distillation afforded 62 mg (H4(/~) of the ketone
as a colorless oil, which gave a single spot on tlC: 17 n24D 1.5155
(lit.]S n20 D 1..5168); nmr & 2.13 (singlet, 3 H, methyl), 3.69
(singlet, 2 H, methylene), and 7.28 (singlet, 5 H, aromatic).
The inframd spectrum contained a C=O stretching frequency
at 5.81 p.
l,l-Diph,enylacetone.-To a solution of HO mg (0040 mmol) of
methyl a-methyl-tl-phenylstyrylsulfide in 4 ml of 3: 1 acetonitrile
water was added 217 mg (O.RO mmol) of mercuric chloride in 4
ml of the same solvent mixture. The homogeneous solulion was
refluxed (w. H2) for 41 hr, during which time the colorless
mercury m~rcaptide precipitated. Work-up as above and short
path distiliation afforded 72 mg (86%) of a colorles.'l liquid,
which solidified upon cooling, mp 4a.5-45.0 (lit. ll mp 4:;-46).
(1.5) Such homoallrlic coupling to cis-oriented protons has precedent; for
example, Ii. A. l'ieville and I. G. Nip;llm [Tetrahedron LeU . 837 (1969) I
have noted ';hat the methyl group .t C, of compound i is a triplet, J - 1.0
cps, due to ('Dupling to tht- C~ protonA.

?a

COOCH.1

(16) See Ie Nakanishi, "Prsc1if'Rl In{rared A .. ;rption Spectroscopy/'

lL...-l\iC'u-D'lY, I i.J~'., San Fraucisco. ! ',,-JiL, Hl62, P 165.
(17} S:!ir'i. '1.! l nw'hylen l ' ddurid~-cy('luhe,,) OH elucnt..
(1';,) (), \', .~:;tll:il, Ar,I" "..-je;'l.., 332, ::H\S (HHHL

The product gave a single spot on tlc: 17 nmr & 2.23 (singlet, 3 H,
methyl), 5.15 (singlet, 1 H, methine), and 7.:n (singlet, 10 H,
aromatic). The infrared spectrum contained a C=O band at

5.R2

p.

2-0ctanone.-To 111 mg (0.70 mmol) of methyl I-methyl-I

heptenyl sulfide in 4 ml of 3: 1 acetonitrile-water was added :180
mg (1.40 mmol) of mercuric chloride in a ml of the same solvent
system. A colorless precipitate appeared immediately on mixing.
After (l hr of stirring at room temperature, the milky mixl.lre WM
ftltered through Hyflo Super Cel, with thorough ether washing.
The filtrate was washed with nqu('olls sodium- biearb.m:lte and
then with brine, dried over anhydrous magnesiulll sulfate, and
concentrated on the rotary evaporat.or. The resulting oil was
passed through a short silica gel column (methylene chloride
eluent) to remove mercuric salts, affording, after rcmoval of
solvent, 67 mg (74%) of liquid whosc infrared and nmr spectra
were identical with those of authentic 2-octanone, n"D 1.4145
(lit.'o n'oo 104161). The ketone gave /l single spot on tlcY
Cyc10hexyl Methyl Ketone .-To 19ii mg (1.25 mmol) of methyl
(l-cyclohexylidene)ethyl sulfide ill S ml of a: 1 acetonitrile-water
was added a solution of 671l mg (2.5 mmol) of mercuric chloride
in 5 ml of the same soh'ellt system. After 20 hr of stirring at
room temperature, the mixture (a colorless precipitate with a pink
8upernatent Jiquid) W/lci filtered through Hyflo Super Cel, with
generous ether washing. The filtrate was washed with aqueouS
sodium bicarbonate and then brine and dried over anhydrous
magnesium sulfate. Concentration by rotary evaporator and
short-path distillation afforded 123 mg (7K%) of the clear, color
less liquid ketone, n 25D 1.4:i13 (lit. z1 n 20n 1.4;'):)0). The product
gave a single spot on tlC: 17 nmr (Cel,) Il 1.:; (broad multiplet,
10 H, alicyclic), 2.03 (singlet, 31I, methyl), and 2.tH (multiplet,
1 II, methine)" The infrared spectrum contained a (>=0 band
at 5.83 p.
Cyclohexyl n-Octyl Ketone.-A nonhomogeneous mixture of
1()2 mg (0.40 mmol) of methyl (l-cyclohcxylidenc)nonyl sulfide lil
o ml of 5: 1 acetonitrile-water was treated with 21 i mg (O.SO
mmol) of mercuric chloride in 3 ml of the same solvent system.
The eloudy reactioll lIlixtnre was heated at :;0 for 26 hr, g'iving II
colorless precipitate and a pink, supernatent liquid. Work-up as
above and short-path distillation gave 83 mg (92%) of the ketone
as a colorless liquid, n251l 1.4:;75 (lit. n 20D 1.45R5,!2 1.46(013 ). A
single spot was observed on tlc: 17 nmr Il 0.8-2.0, including fl
poorly resolved triplet at 0.9:J and a broad band at 1.27 125 II),
and 2.37 (multiplet, 3 H, protons a to carbonyl). The infrared
speetrum contained a C= -0 balld at 5.82 p.

Registry No.--4a, 22966-40-1; 4h, 22966-41-2;

protonatcd 6a, 22966-42-3; 7a-E, 22951-1S-4; 7h-E,
22951-19-5; 7a-Z, 22966-52-5; 7h-Z, 22966-.5:3-6; methyl
a-methYl-,B-phenylst.yryl sulfide, 220G()-:~-i; methyl
(l-cyclohexylidelle)ethy I sulfide, 22966-44-:j; methyl
(l-cyclohexylidene)nonyl sulfide. 22!HiG-4:i-G; methyl
(1-cyclopenty lidene) ethy I sulfide, 22929-24-4.
Acknowledgments.-This work v;m; supported by the
National Institutes of Health. Weare grateful to
Mr. B. W. Erickson for his a;:sistance in the early stage~
of this work.
(19) R. S. Yost an,l C. R. lIall.er, J. Amer. Chm. Sor . 69, 2325 (1"17),
This ketone is reported t.o cr:, stallize in two lorIng, mp -:16 and 61; 8';C
R. 3toermer, Chern. Ber., J~, 2288 (11106).
(20) N. A. Lange, '"1I"ndb()'Jk of Chemi.try." lOlh ed. l\IcGrawHill
Houk Co., Inc., New York, N. Y'I Hl67, P 13:':2.
(21) N. ll, Zelinsky sud L. ~I. Tar~~:,wwa. ,,'in.n. Chfm., 1508, 115 (!tI3l}.