ST'ILLIAME. TRUCE A K D FRED D. HOERGER
2496
two molecules of I by elimitiation of HF. Its structure was not elucidated. The mother liquor of the above product was fractionated i n zacuo. A light yellow oil distilled a t 130" (0.4 mm.), which solidified spontaneousb-. From methanol, white plates of m.p. 59-60" were obtained; yield 7 g. The ultraviolet spectrum of this compound ( I Y ) was practically identical with t h a t of benzalacetophenone.
Vol. 77
Anal. Calcd. for C16HIIFO:C, 79.6; H , 1.9. Found: C, 79.6; H , 5 . 1 . The 2,1-dillitrophen?.lhy~~r~zo,lc of this kctotle crystallized fronl butyl acetate in needles of 1n.p. 271-275'. calcrl, forc ! ~ ~ ~C, ~63.1; F ~H , ~3.7.o pound: ~ : " B 2 ' 3 ; H ' 3'r5' JERUSALEM, ISRAEL
[COL'TRIBL~TIOXFROM THE DEPARTMENT O F CHEMISTRY, PURDUE 1-NIVERSITT]
The Chemistry of Sultones. 11. Alkylations of Organometallic and Related Compounds by Sultonesl BY WILLLW E. TRUCE .\ND FRED D. HOERGER? RECEIVED O C r O B E R 1, 1F)llithium a n d the sodium derivatives of diethyl malonate, ethyl acetoacetate and dibenzol lmethane are alkyldted readil! by 4-hydroxJ -1-butanesulfonic acid sultone. The reaction of 4-hydroxy-1-butanesulfonicacid sultone with phenylmagnesium bromide produces both magnesium 4-phenyl-lbutanesulfonate and magnesium 4-bromo-1-butanesulfonate. The reaction of 2-o-hydrox~ phenylethanesulfonic acid sultone with phenylmagnesium bromide gives o-(P-phenylsulfonylcth> 1)-phenol
Helberger and c o - w o r k e r ~have ~ , ~ shown recently that sultones serve as alkylating agents for a variety of nucleophilic reagents, such as alcohols, alkoxides, salts of inorganic and organic acids, amines and the sodium derivative of fluorene. The products of these reactions are substituted alkanesulfonates, but their structures were not established ; presumably they arise according to the equation
In the first paper of this series5it was shown that C-alkylations are accomplished readily by the use of sultones as alkylating agents in the FriedelCrafts reaction. Since alkyl sulfonates serve as carbon-carbon alkylating agents for organometallic compounds and since the reactions of sultones with nucleophilic reagents closely resemble the reactions of alkyl sulfonates, it seemed probable that sultones could serve as alkylating agents for carbonMX L(CR,),SO,A' --+ X(CR,),SOJI carbon alkylations of organometallic and related In order to establish definitely the nature of the compounds. Carbon-carbon alkylation occurred readily in products obtained from the reactions of sultones with nucleophilic reagents, the reactions of so- the reactions of both phenylethynylsodium and ndium benzenesulfinate and sodium ethoxide with 4- butyllithium with 4-hydroxy-1-butanesulfonicacid hydroxy-1-butanesulfonicacid sultone (I) were sultone (I). IVith phenylethynylsodium, an 85% studied. With sodium ethoxide, a 91% yield of yield of crude sodium 6-phenyl-5-hexyne-1-sulfonsodium 4-ethoxy-1-butanesulfonate(11) was ob- ate (IV) was obtained; pur fication, however, retained. This product was characterized by com- duced the yield to about 50%. The structure of IV parison of its 9-chloro-S-benzylthiuronium salt was established by analysis of its p-chloro-S-benwith an independently synthesized specimen. zylthiuronium derivative and by catalytic reducThe independent synthesis involved the reaction of tion to sodium 6-phenyl-1-hexanesulfonate. The 4-chloro-1-ethoxybutane with aqueous sodium sul- latter compound was synthesized independently fite. The reaction of sodium benzenesulfinate with from G-phenyl-1-brornobutane and sodium sulfite. I gave a 53yp yield of sodium 3-phenylsulfonyl-l- The reaction of n-butyllithium with I gave a 58%) butanesulfonate (111). The S-benzylthiuronium yield of the very hygroscopic lithium l-octanesulfonate which was characterized by comparison of MS r(Cr&)4sO!7 ---+ S(CH?)4SOJM L_______, its p-chloro-S-benzylthiuronium salt with an inde11, S = OCsHj; M = S a pendently synthesized specimen. I 111, X = S02CsHs;M = ATa II-,N = CsHjC=C; 11 = S a The reaction of phenylrnagnesium bromide with L-, S = G H , ; M = Li 3-hydroxy-1-butanesulfonic acid sultone produced a derivative of 111 was identical with the correspond- mixture of sulfonates, magnesium 3-bromo-1-buing derivative of a sulfonate independently synthe- tanesulfonate (VI) and magnesium 4-phenyl-1-busized from 4-chloro-1-phenylsulfonylbutaneand tanesulfonate (VII). IVhen two moles of the sultone sodium sulfite. These reactions confirm the struc- I and one mole of Grignard reagent were employed, tures assigned by Helberger to the alkylation products of sultones and establish a similarity in the CsH5MgBr + '-(CH?)rSOa-' reactions of sultones and alkyl sulfonates with nucleophilic reagents.
+
+
--f
(1) Abstracted from a portion of t h e Ph.D. Dissertation of F. D. Hoerger, Purdue University, 1955. ( 2 ) National Science Foundation Predoctoral Fellow, I%%-1954. (3) J. H. Helberger, r t ai., Ai7n., 665, 22 (1949); 562, 23 (1949); 686, 147 (19.34): 586, 158 (19.54). (4) J . H. Helberger, Reiciisumt T t ' i r f s h u f ~ u ~ ~ f Chem. bau B r . P l u f XI., 16 (U. S. Office of Publication Board, P. B. 52013) 289 (1942).
1, Sa2COg 1.1
2, HC1
MgBrn
Br(CHl)+SO!H ----+ - HBr
I -----+Vr
May 5 , 19%
ALKYLATIONS OF ORGANOMETALLIC COMPOUNDS BY SULTONES
the mixture of sulfonates was obtained in 90% yield. By fractional crystallization of this mixture, it was possible t o isolate magnesium 4-phenyl-1-butanesulfonate (VII), identified by preparation of its sulfonamide5 and p-chloro-S-benzylthiuronium s a k 5 I t was not possible to isolate the bromosulfonate VI from the mixture of sulfonates. The presence of this sulfonate was shown by converting the crude reaction product to a mixture of sulfonic acids; by heating this mixture of sulfonic acids under vacuum, 4-bromo-1-butanesulfonic acid lost the elements of hydrogen bromide and was converted t o 4-hydroxy-1-butanesulfonicacid sultone (I) which distilled away from the 4-phenyl-1-butanesulfonic acid. Even when only one mole of sultone per mole of Grignard reagent was employed, both VI and VI1 were formed. This suggested that magnesium bromide also should react readily with 4-hydroxy-lbutanesulfonic acid sultone. Under the same reaction conditions as were employed with phenylmagnesium bromide, magnesium bromide and the sultone gave a 9770 yield of magnesium 4-bromo-lbutanesulfonate (VI). The formation of a mixture of sulfonates from the reaction of phenylmagnesium bromide with 4-hydroxy- 1-butanesulfonic acid sultone is analogous to the formation of both hydrocarbons and alkyl halides in the reaction of Grignard reagents with alkyl sulfonate^.^-^ The latter reaction has been shown to proceed primarily according to the following equation regardless of whether one or two moles of alkyl sulfonate are used per mole of Grignard reagent ArS03R
+ R’MgX +RR’ + RX + (ArSO3)2Mg
A side reaction in the formation of hydrocarbons and alkyl halides in the reaction of Grignard reagents with alkyl sulfonates is sulfone formationlO*ll ArS08R
+ R’MgX
----t
ArS02R‘
+ ROMgX
However, no evidence for sulfone formation was observed in the reaction of phenylmagnesium bromide with 4-hydroxy-1-butanesulfonicacid sultone. In contrast to the behavior of 4-hydroxy-l-b~tanesulfonic acid sultone with phenylmagnesium bromide, Mustafa and co-workers12report that several derivatives of 1-naphthol-8-sulfonic acid sultone react with Grignard reagents to give sulfones. Likewise, we found that the reaction of phenylmagnesium bromide with 2-o-hydroxyphenylethanesulfonic acid sultone (VITI) gave a 62% yield of a sulfone, o-(P-phenylsulfonylethy1)-phenol(IX)
VI11
IX
is due to the fact that the sulfonate grouping would have to be displaced from an aromatic carbon atom in VI11 in order for alkylation t o occur; this is a much more difficult process than the displacement of the sulfonate grouping from an aliphatic carbon atom. The sodium derivative of diethyl malonate was alkylated with 4-hydroxy-1-butanesulfonic acid sultone to give a 95% yield of sodium 5,S-dicarbethoxy-1-pentanesulfonate. This sulfonate was identified by its saponification equivalent and by comparison of its p-chloro-S-benzylthiuronium derivative with an independently synthesized specimen. 4-Hydroxy-1-pentanesulfonic acid sultone and the sodium salt of diethyl malonate gave a sulfonate in 93% yield. On the basis of saponification equivalent and analysis of its p-chloro-S-benzylthiuronium derivative and by analogy with the above alkylation of diethyl malonate, this sulfonate may be assigned the structure of sodium 5,5-dicarbethoxy-4methyl- 1-pentanesulfonate. The sodium salt of ethyl acetoacetate also was alkylated readily with 4-hydroxy-1-butanesulfonic acid sultone to give an 82y0 yield of crude sodium 5-carbethoxy-6-oxo-1-heptanesulfonate (X). This sulfonate could not be purified by crystallization from water or alcohol and the saponification equivalent was in error by about By0. The identity of the product was established, however, by hydrolysis and decarboxylation to sodium 6-oxo-1-heptanesulfonate (XI). The latter compound gave a pchloro-S-benzylthiuroniurn salt identical with an independently synthesized specimen. [CH&!OCHCO?Et]
Na
+ L(C H z ) 4 S 0 ,+ ~
I
COiEt
I
CH3COCH(CH2)~S0&a
&SO4
CH,CO( CHz)5S03Na
HzO
X
XI
The reaction of the sodium salt of dibenzoylmethacid sultone ane with 4-hydroxy-1-butanesulfonic gave a sulfonate in 54% yield. Although i t was not possible to obtain pure derivatives of this sulfonate, it was shown to be primarily sodium 5,5-dibenzoyl-1-pentanesulfonate (XII); cleavage of the sulfonate with dilute sodium hydroxide gave a 52% yield of benzoic acid and a 50% yield of sodium 5benzoyl-1-pentanesulfonate (XIII), The identity of XI11 was established by analysis of its p-chloroS-benzylthiuronium salt and by Clemmensen reduction to sodium 6-phenyl-1-hexanesulfonate (XIV) . The p-chloro-S-benzylthiuronium derivative of XIV was identical with the p-chloro-S-benzylthiuronium salt of the sulfonate obtained from
The difference in the mode of reaction of the sultones I and VI11 with phenylmagnesium bromide (6) C. M. Suter and H. L. Gerhart, THISJOURNAL, 67, 107 (1935). (7) H . Gilman and L. L. Heck, ibid., 8 0 , 2223 (1928). (8) J. W. Copenhaver, el al., ibid., 67, 1312 (1935). (9) H. Gilman and H. Robinson, “Organic Syntheses,” Coll. Vol. 11, John Wiley and Sons, Inc., N e w York, N.Y.,1943, p. 47. (10) H. Gilman and L. L. Heck, THISJOURNAL, 60, 2229 (1928). (11) H. Gilman and J. Robinson, Bull. SOC. ehim., 46, 636 (1929). 384 (1949); 2151 (1949); 1339 (12) A. Mustafa, e1 o l . , J . Chcm. SOC., (1952).
2497
1
XI1
XI11
XIV
2498
LVILLIAhl
E. TRUCE .4ND FRED D. HOERGER
Irol. i 7
the catalytic reduction of sodium 6-phenyl-3-hex- was distilled, and the residual oil was poured iiito 1.70 ml. of water. After extraction of the organic layer with ether ant1 yne-1-sulfonate (IV). drying over magnesium sulfate, di?tilIation g:i\-e 11.5 g . AbellI3reports that in the alkylation of dibenzoyl- (41% yield) of 4-chloro-1-phenylsulfon~lbutane, 11.p. 188methane with methyl iodide some ethyl benzoate 182" (3 mm.). An analytical sample, recr>-stallized twice and some phenyl ethyl ketone always are formed; from a mixture of benzene and 60--70" petroleum ether, had prolonged heating of the reaction mixture increases m.p. 55.5-57'. Anal. Calcd. for Clo€II.IC102S: C, 51.61; H, S.67. their formation. Since a longer reaction time was Found: C, 51.75; H , 5.71. used for the reaction of dibenzoylmethane with I A mixture of 8.0 g. (0.034 mole) of 4-chloro-I-phenylthan that reported for the reaction of dibenzoylmeth- sulfonylbutane, 13.1 g. (0.085 mole) of potassium sulfite, ane with methyl iodide, it is quite likely that some 20 ml. of water and 60 ml. of ethylene glycol was refluxed of XI1 is cleaved by sodium ethoxide to give ethyl for 65 hours. The mixture was concentrated to about 50 benzoate and XIII. Thus, the failure to obtain ml. and upon cooling there separated 10.5 g. of potassium uhich Tvas slightly conpure derivatives of the product from the dibenzovl- 4-phenylsulfonyl-1-hutanesulfonate taminated with potassium sulfite. The S-bei~zylthiuronium methane-sultone reaction probably results from XI1 derivative of this sulfonate had m.p. 149-150 . Sodium 6-Phenyl-5-hexyne-l-sulfonate.-This reaction being contaminated with XIII. was carried out under a nitrogei atmosphere. PhenylethynExperimental ylsodium was prepared from 2.3 g. (0.10 g. atom) of finely cut sodium, 20.4 g. (0.20 mole) of phen5-lncetylerie and 150 Sodium 4-Ethoxy-l-butanesulfonate.-To a solution of sodium ethoxide prepared from 2.3 g. (0.10 g. atom) of so- ml. of anhydrous ether according t o the method of Gilman dium and 75 ml. of absolute ethanol was added 13.6 g. (0.10 and Young.18 To this suspension of phe~i~lethyri!lsodium mole) of 4-hydroxy-1-butanesulfonic acid sultonej; the re- mas added dropwise 13.6 g. (0.10 mole) of l-hydroxy-lsulting solution was refluxed for 46 hours. After cooling butanesulfonic acid sultoiie. About 200 ml. of tolueie ivas the mixture and diluting with 150 ml. of ether, the crystal- added and most of the ether mas then removed by distillation. line sulfonate was filtered. After drying in a vacuum oven, The resulting suspension was refluxed with stirring for 18 hours. The precipitated sulfonate w a s filtered and then t h e sulfonate weighed 18.5 g. (91% yield). \yashed twice with ether. The crude, slightly yellow, P-Chloro-S-benzplthiuronium 4-ethoxy-1-butanesulfonate had m.p. 113-114.5'. A mixed m.p. with an independently sulfonate weighed 22.1 g. (S5yo>-ield). This sulfonate was purified by treatment v i t h charcoal and recrystallizatioll synthesized sample (see below) showed no depression. Anal. Calcd. for C14H21ClN~04S~: C, 43.90; H, 6.05; from water or ethanol; the recovery from this sequence was about 60%. N, 7.32. Found: C, 43.98; H, 5.97; N, 7.27. .b-Chloro-S-benzvlthiuroiiium 6-ahenvl-5-hexv:ie-l-sulIndependent Synthesis of Sodium 4-Ethoxy-I-butaneprepared from the above p u r k e d sodium sulfonate, sulfonate.-4-Chloro-l-ethoxybutane was prepared in 50% foAate, had m.p. 151-153'. yield from sodium ethoxide and l-brom0-4-chlorobutane.~~ Anal. Calcd. for C2&~21C1X203S2:C, 51.72; H, 5.38; The chloroether had b.p. 39-41' (6 mm.), f i 2 0 ~1.4258 (lit.'5J6 S, 6.38. Found: C, 54.63; H, 5.58; N, 6.48. b.p. 50' (13 mm.), d 5 1.4278, ~ n% 1.4249). A mixture of Sodium 6-Phenyl-1-hexanesulfonate.-A solution of 1.65 20 g. (0.15 mole) of 4-chloro-l-ethox~-butane,38 g. of sodium sulfite and 130 ml. of water was refluxed with stirring g. of the above sodium 6-phenyl-5-hexyne-I-sulfonate in 80 for 20 hours. The reaction mixture was evaporated to ml. of 50% methanol was hydrogenated over Raney nickel dryness and the resulting residue was extracted with about catalyst at room temperature with an initial hydrogen pres300 ml. of hot absolute alcohol. Concentration of the al- sure of 26 pounds. After hydrogen uptake was completed, the catalyst i n s filtered and the filtrate was concentrated cohol gave 14.5 g. (47% yield) of sodium 4-ethoxy-l-butanesulfonate whose fi-chloro-S-benzvlthiuronium derivative t o about 15 ml. From this solution was obtained an 84% yield of p-chloro-S-benzylthiuronium 6-phenyl-1-hexanehad m.p. 113-114.5°. sulfonate, m.p. 118-152". A further recrystallization Sodium 4-Phenylsulfonyl-1-butanesulfonate.-A solution raised the m.p. t o 152-153.5". of 20.0 R. (0.10 mole) of sodium benzenesulfinate dihvdrate." 140 ml, of dimethylformamide and 13.6 g. (0.10 mole) of .InnE. Cslctl. for C20H&INnO:&: C , 54.22; €1, 6.14; 4-hydroxy-1-butanesulfonic acid sultone was heated with N,6.33. Found: C , 54.48; H,6.40; N,O.48. stirring on the steam-cone for 24 hours. After removal of A mixed m.p. with independently synthesized p-chlorothe dimethylformamide under diminished pressure, the re- S-benzylthiuronium 6-pheii~-l-l-hexanesulfonate (see besulting residue was washed twice with ether and then was low) was not depressed; a mixed m.p. with p-ch1oro-Sdissolved in water. Concentration of this aqueous solution benzylthiuronium 6-phe11~1-5-hexyne-l-sulfonate, however, gave two crops of crystalline sulfonate totaling 12.3 g. was depressed to 116-137'. Complete evaporation of the filtrate left a residue which was Independent Synthesis of Sodium 6-Phenyl-I-hexanecrystallized from absolute alcohol to give an additional 3.5 sulfonate.--y-Phenylbutyric acid19 was converted t o 4g. of sulfonate (total yield of 53%). phenyl-1-bromobutane according to the procedures deS-Benzylthiuronium 4-phenplsulfonyl-l-butanesulfonate, scribed by Truce and Milionis.20 6-Phenyl-l-hexanol, b."; recrystallized from dilute ethanol, had m.p. 149-150'. A 135-138° (2.5 mm.), fiZ5D 1.5083 (lit.*1s*2h.p. 140-111 mixed m.p. with an independently synthesized sample (see ( 3 mm.), 160-161° (13 mrn.)), was prepared in 56% yield below) showed no depression. from the Grignard reagent of 4-pheii!l-l-bromobLitaiie and Anal. Calcd. for C18H24?IT206Ej3: C, 48.63; H, 5.44; ?;, ethylene oxide according t o the method of Dreger.2" From 6.30. Found: C , 48.62; H, 5.60; Ti, 6.37. this alcohol and phosphorus tribrornide was prepared, :ICSeveral attempts were made t o carry out the reaction of cordirig t o the procedure of Shriner and Young,246-pheuyl-1sodium benzenesulfinate in absolute alcohol, aqueous alco- bromohexane (70% yield), b.p. 120-123' ( 2 m m . ) . ? I % hol and acetone as solvents. In refluxing acetone, little or 1.5250 (lit.22b.p. 160-161' ( 1 7 m m . ) ) . no reaction occurred. Although reaction occurred in ethRefluxing a mixture of 18.5 g. (0.07'7 mole) of 6-phenyl-lanol and aqueous ethanol, alcoholysis and hydrolysis of the bromohexane, 23.1 g. (0.231 mole) of sodium sulfite and 190 sultone also occurred; consequently, the product was diffi- ml. of water for 21 hours gave 17.4 g. (86y0 yield) of sodium cult to purify. 6-phenyl-I-hexanesulfonate; the p-chloro-S-benzylthiuroIndependent Synthesis of 4-Phenylsulfonyl-I-butanenium salt had m.p. 132.5-153.3" after crystallization from sulfonate.-A mixture of 30 g. (0.15 mole) of sodium bendilute ethanol. zenesulfinate dihydrate, 76 g. (0.60 mole) of 1,4-dichloro- ______(18) H. Gilman a n d R. V . Young, J. Org. Chem., 1, 315 (198ii). butane and 200 ml. of 95% ethanol was refluxed with stirring (19) W.E. T r u c e a n d C. E. Olson, THISJ O U R N A L , 1 4 , 4721 (1952). for 22 hours. The mixture was filtered. most of the ethanol (13) R. D. Ahell, J . Chem. SOL, 989 (1912). (14) D. Starr a n d R. M , Hixon, THISJ O U R N A L 56, 1593 (1934). (13) H. N o r m a n t , Compl. r e n d . , 231, 909 (1951). (16) hf. H. Palomaa and R. Jansson, Ber., 64B,1606 (1031). JOURNAL, 60, 792 (1928). (17) S. Krishna a n d H. Singh, THIS
( 2 0 ) W. E. T r u c e a n d J . P. Slilionis, ibid., 74, 974 (1952). (21) J. B. C o n a n t a n d W.R. Kirner, i b i d . , 46, 241 fl(4241. (22) J. V. Braun, Ber., 44, 287 (1911). (23) E. E. Dreger, "Orxanic Syntheses," Coll. Vol. I. John TVilry a n d Sons, Inc., Piew York, iY.Y . , 1041, p. 300. (24) I
