J . Org. Chem., Vol. 44, No. 26, 1979 4953
Hydride Transfer from 1,4-Dihydropyridines ether gave pure la (30mg, 15%): mp 188-189 "C; NMR7 (acetone-d6 DzO) d 3.04 (s, 3,CH3), 4.38 (d of q, 1, H3),4.78 (d, 1, H4), 6.08 (d of d, 1,Hz),7.25-8.25(m, 7,H1 and aromatic), 8.73 (s, 1, Hp); J1,2 = 10, J 2 , 3 = 3,53.4 = 12 Hz. trans-3,4-Dihydroxy-anti1,2-epoxy1,2,3,4-tetrahydro-7methylbenz[a]anthracene (2). A solution of la (23mg, 0.083 mmol) and rn-chloroperbenzoicacid (230mg) in 25 mL of dry THF was stirred under Nz for 2 h at room temperature. The solution was diluted with ether, washed twice with 10% aqueous NaOH solution and water, and dried. Evaporation of the solvent (avoiding heating), followed by trituration with ether, gave 2 (13 mg, 57%) as a white solid: mp 183-185 "C; NMR ( a ~ e t 0 n e - d ~ + D20) 270 MHz 6 3.0 (9, 3,CH3), 4.13 (4, I, HZ), 4.31 (q, 1, H3), 4.88 (d, 1, H4), 5.40 (d, 1, H1),7.38-8.41 (m, 6,aromatic), 8.85 (s, 1, H12); 51,2= 4.7,J 3 , 4 =: 8.0,52,3= 1.5Hz. trans- 1,2-Dihydroxyan ti -3,4-epoxy1,2,3,4-tetrahydro-7methylbenz[a]anthraoene (4a). Epoxidation of 3a (23 mg, 0.08 mmol) was carried out by the procedure employed for the analogous reactions of la. Evaporation of the solvent (avoiding heating) gave crude 4a (20mg, 74%) which showed one major peak (80%) on LC on a Ihpont Si1 column (THF-heptane, 4555). The major peak was collected and identified as 3a: NMR (acetone-d6 + D20)'270MHz, 6 3.14 (s, 3,CH3),4.03 (d, 1, HB),4.28
+
(d, 1, H4), 4.72 (br s, 1, HJ, 5.42 (apparent s, 1, HI), 7.53-7.59 (m, 2,H g , d 7.75 (d, 1, HE,), 8.17 (d, 1, H d , 8.37 (d, 1, H A 8.42 (d, 1, Hs), 8.82 (s, 1,HIJ; J1,2 1,J 2 , 3 = 0.98,53,4 = 3.73,J5,6 = 8.96,J8,9 = 8.11,Jlo,ll = 8.63 Hz.
Acknowledgment. T h i s investigation was supported b y G r a n t s CA 11968 and CA 14599 and research contract No. CP 033385 f r o m t h e N a t i o n a l Cancer Institute, DHEW. We also thank Professor Melvin S. Newman for his k i n d consent to delay publication of his related manuscript t o permit simultaneous publication with this paper. Registry No. la, 64521-14-8; lb, 71988-88-0; 2,64625-66-7; 3a, 64521-13-7;3b, 71988-89-1;5, 72016-70-7;6a, 71988-90-4;6b, 6d, 71988-93-7; 7,71988-94-8; 8a,7198871988-91-5; 6c,71988-92-6; 95-9;9a,71988-96-0; 9b,71988-97-1; 10,71964-75-5; 11,71964-76-6; 12,71964-77-7; 13,71988-98-2; 14a,71988-99-3; 14b,71989-00-9; 14c, 71989-01-0; 15, 71989-02-1;16, 71989-03-2; 17a, 71989.04-3;17b, 3,4,7,12-tetrahydro-7-methylbenz[a]anthracene, 7198971989-05-4; 06-5;1,2,7,12-tetrahydro-7-methylbenz[a]anthracene, 72016-71-8; 2-acetoxy-3,4-dihydro-7-methylbenz[a]anthracene, 72016-72-9;7methylbenz[a]anthracene, 2541-69-7;benz[a]anthracene, 56-55-3; 7-bromobenz[a]anthracene, 32795-84-9.
Hydride Transfer from 1,4-Dihydropyridines to sp3-HybridizedCarbon in Sulfonium Salts and Activated Halides. Studies with NAD(P)H Models'
'T.J. v a n Bergen,2a David M. Hedstrand,2bW i m H. Kruizinga, and R i c h a r d M. Kellogg* Departmeni' of Organic Chemistry, University of Groningen, Nijenborgh 9747 AG, Groningen, T h e Netherlands
Received July 10, 1979 The reactions of 1,2,6-trimethyl-3,5-bis(methoxycarbonyl)-l,4-dihydropyridine (2a),l-methyl-3,5-bis(methoxycarbonyl 1- 1,4-dihydropyridine (2b),and l-benzyl-3-acetamido-1,4-dihydropyridine (1)with various sulfonium salts have been investigated. On thermal (60 "C) activation 2a,b react with, for example, methylphenacylphenylsulfonium tetrafluoroborate (3b)to give the respective pyridinium salts, acetophenone, and phenyl methyl sulfide. There is some competing isomerization of the 1,4-dihydropyridines to their (nonreactive) 1,2-dihydro isomers, this being catalyzed by the pyridinium salt formed on reduction of the sulfonium salt. Phenacyl-, acetonyl-, and in some cases benzylsulfonium salts can be reduced. The group to which hydride transfer takes place should be electron deficient. These reductions can be initiated at rwm temperature with visible light (at rmm temperature pyridinium :salt induced isomerization of the 1,4-dihydropyridine to its 1,2 isomer occurs only over a period of several days:i. The effect of visible light can be enhanced greatly by adding small amounts of dyes to the reaction mixtures. Eosin sodium salt, tetraphenylporphine, and R~"(2,2'-bpy)~Cl~ are all capable of increasing the rate of reduction; the last dye is by far the most effective. The results of mechanistic investigations are consistent with the hypothesis that the light-induced reductions are one-electron transfer reactions. In some cases there appears to be a separate thermal mechanism not sensitive to either light or sensitizers. Some sulfonium salts react with dihydropyridines to give the pyridinium salt and sulfide in less than quantitative yield and no reduction products from the sulfonium salt. As determined for the case of the reaction of bromomalonitrile with 1, and presumably also for other reactions, alkylation of an enamine carbon in the dihydropyridine is involved; the resulting iminium salt has been trapped by methanol and characterized. T h e recognition that a 1,4-dihydronicotinamide (1) is the chemically active component of N A D ( P ) H 3 caused a surge of interest in 1,4-dihydropyridines in general. Derivatives of l a r e t h e most closely related i n s t r u c t u r e t o the coenzyme. However, application of t h e tool of struct u r a l modification for mechanistic investigation is somew h a t hampered for derivatives of 1, owing t o serious synthetic difficulties in obtaining such compound^.^ A partial
H
H
H
H
R'OiC&Co2R3
b N C O N H 2
R'
I
1
R
9'
-1
2 -
a ) CH2CgH5
a 1 R ' - R 2 = C H 3 , R'zCiH5
b ) R t= R ' r C H 3
(1) Part 9 on the chemiiitry of dihydropyridines. For part 7 see R. H. van der Veen, R. M. Kellogg, A. Vos, and T. J. van Bergen, J. Chem. SOC., Chem. Commun., 923 (1978); for part 8 see J. G. de Vries and R. M. Kellogg, J . Am. Chem. Soc., 101, 2759 (1979). (2) (a) The Dow Chemical Co., Terneuzen, The Netherlands; (b) Undergraduate Exchange Situdent from Hope College, Holland, Michigan. (3) Reviews of original literature: (a) H. Sund, H. Diekmann, and K. Wallenfels, Adv. Enrymol. Relat. Subj. Biochem., 26, 115 (1964); (b) T. C. Bruice and S. J. Benkovic, "Bioorganic Mechanisms", Vol. 2, W. A. Benjamin, New York, 1966, p 301.
0022-3263/79/1944-4953$01.00/0
R'
R'=H
solution to t h i s problem is found with t h e symmetrically substituted "Hantzsch esters" (2), which a r e readily synthesized with considerable variation i n structure. (4) See, for example, F. Brody and P. R. Ruby, in "Heterocyclic Compounds", Vol. 14l, E. Klingsberg, Ed., Interscience, New York, 1960, p 99.
1979 American Chemical Society
4954
J. Org. Chem., Vol. 44, No. 26, 1979
van Bergen et al.
Table I. R e d u c t i o n s by 1 , 4 - D i h y d r o p y r i d i n e s (DHP) % pyr-
s u b s t r a t e R1S’R2R3,BF;
compd
1,4-DHP 2a‘
R’ C,H,COCH, C H ,C0 CH 4-CH,OC6H,COCH, 4-CH, OC, H,COCH, 3-CH,OC6H,COCH, 2-CH,OC,H,COCH, 4-NO2C,H,COCH, 3-NO2C,H,COCH, 2-NO2C,H,COCH, CH CO C H CH, c, H ,CH C,H ,CHI C,H, CH C,H,COCH, ~
2ba
R2 CH, CH, C,H, C, H, C,H, C,H, C6H5 C6H5
6‘
H5
C6H5 ‘bHS
CH3 C6H5 C6HS
C6HS
R3
no.
CH, C,H, C,H, CH, CH, CH, CH, CH, CII, CH, C,H, CH, CH3 C,H, CH3
3a 3b 3c 3d 3e 3f
3g 3h 3i 3j 3k 31
3m 3n 3b
idin’um salt 40 37
60 40 25 47 90 70 61 13 18
4 42 54 60
% reduction prod
R’H 33 34 b b
2o c * RBr
Br
\.
,SCH2~H2;HC3‘
c
hH:
hH3*
-
-
d; e
$,CUI
\”
6 a
7 Cs*ICh2
b
R-C6W5COCk2
4
(18) See, for example, E. Block, “Reactions of Organosulfur Compounds”, Academic Press, New York, 1978, pp 118-24. (19) A mixture of the diastereomeric sulfonium bromides from free dl-methionine was prepared by the method of (a) T. Hashimoto, H. Kitano, and K. Fukui, Nippon Kagaku Zasshi,89, 810 (1968); Chem. Abstr., 70, 28546 (1969). The spontaneous decomposition is known; see, for examde: (b) T. F. Lavine. N. F. Flovl. and M. S. Cammaroti. J . Biol. Chem., 207, 107 (1954); (c) F. Schlencand J. L Damko, Radiat. Res., 16, 327 (1962).
van Bergen et al.
4956 J. Org. Chem., Vol. 44, No. 26, 1979
thionine by esterification and acylation on nitrogen; subsequent alkylation gave the sulfonium salts 8a,b as mixtures of diastereomers, which reacted smoothly with 2c with the results shown in eq 5. Under the conditions used
CHIC8HS
CH2C6HS
14
EA
171
:",sC~~C*>C~c:2CIl NUC~CH,
9 C3,B '$SF'
R'C?>
t
'8
b:5Cv,
.
p'CH,C#IC3CC>tY,
hWCOCY,
I
0
.,.
125'1.
is,
-I
3 +:",3?v,:
',.'.I
NiO..)
?'a,.,
R$:C*,S
CH302CCH2> CH3COCH2> CH, in close analogy with the order derived from Table I. In separate experiments we found that salts 17 and 18, U
II
0
f i fc
/
E -
5
4
E)
C6H5CCH2N ( C H 3 I 3 .CiO,
2
2
'
1
2
0
19
a) X = Br b)X=CI
neither of which give characterizable products in thermal reactions with 2a (part A), are reduced to acetophenone in 60 and 16% yield, respectively, on irradiation in the presence of Ru"(bpy),C12. Likewise, the 4-nitrobenzyl halides 19a,b are reduced smoothly by 2a with light and Run(bpy),C1, to 4-nitrotoluene. The corresponding benzyl halides are unreactive. The halides 19a,b are known to be good substrates for one-electron reductions.26 The ylide 20 derived from 3b failed to react with 2a with or without light and/or sensitizers; 20 can therefore reasonably be eliminated as a possible intermediate. The reaction of 2a with 3b can have chain character as demonstrated by a dark reaction at 55 "C (little spontaneous reaction occurs under these circumstances) in the presence of azobis(isobutyronitri1e) (AIBN). The chain length (moles of acetophenone produced per atom of initiator) is approximately 10. Reactions in the presence of Ru"(bpy),Cl, lend themselves well to study, owing to the remarkable properties of this inorganic sensitizer,27 which in CH3CN has a charge-transfer absorption at 450 nm and, moreover, is luminescent. The excited state derived from absorption in this band can donate an electron to electron-deficient substrates or accept an electron (or hydrogen atom) from electron-rich substrates. Both processes can be monitored by quenching of the luminescence of the complex. Much to our surprise we found that in carefully degassed CH3CN solutions neither 3b, an electron-deficient potential quencher, nor 2a, an electron-rich potential quencher, had any effect on the luminescence of Ru"(bpy),Cl, (Figure 1). Because the reaction of 2a with 3b has characteristics of a one-electron-transfer reaction, we had expected that the one-electron transfer of Ru"(bpy)&12 would be involved in the acceleration of this reaction. A possible solution to this dilemma was found in the following observation. After removal of the solvent after completion of the reaction of 2a with 3b in the presence of Run(bpy),C12,a very tiny nitrile absorption was observed in the infrared spectrum at 2250 cm-'. Careful GLC and 'H NMR analysis revealed that this absorption was due to a trace amount of succinonitrile. On (27) For a discussion of recent developments with RuII(bpy!gP+ and derivatives thereof, see: ((a)G. Sprintschnik, H. W. Sprintschnik, P. P. Kirsch, and D. G. Whitten, J . Am. Chem. Soc., 99, 4947 (1977); (b) J. N. Demas and A. W. Adamson, ibid.,95,5159 (1973): (c) G. Navon and N. Sutin, Inorg. Chem., 13, 2159 (1974); (d) G. S. Lawrence and V. Balzani, ibid., 13, 2976 (1974); (e) C. R. Bock, T. J. Meyer. and D. G. Whitten, J . Am. Chem. Soc., 96,4710 (1974); (D C. R. Bock, T. J. Meyer, and D. G. Whitten, ibid..97, 2909 (1975).
e
6
L
I ^
(
J
.'
concentrat c-
r,,,,,3er
Figure 1. Quenching of R~"(bpy),~+ luminescence: = 1,4dinitrobenzene, k , = 8.8 X lo9 L mol-' s-l with T~ = 0.88 X 10" s for Rull(bpy)Sz+ (lit.27fk , = 6.56 X lo9 L mol-' s-l in degassed CH,CN);
0 =
3b; A = 2a.
irradiation of R~"(bpy)~C1,2~ alone in CH3CN for several hours larger quantities (roughly 1 equiv of succinonitrile/equiv of sensitizer) were found. Succinonitrile has also been reported to be a trace product in the photochemical reactions of a derivative of Run(bpy)z+with triethylamine in acetonitrile.28b One possible interpretation of our observations is that an excited but nonluminescent state of Ru"(bpy),2+ abstracts a hydrogen atom from acetonitrile, and the radical CH2CN, like the radical (CH3)&CN from AIBN, initiates the reaction of 2a with 3b, most likely by hydrogen atom abstraction from the 4-position of 2a. In eq 9-15 a working hypothesis is given for the mechanism of the reaction.% The precise timing of the various 2 -
R u l ! l i ( b py,
23)
2'
+
-
----
R ~ I ! I I ( ~ ~ ~ I ~ H
OH
I ClH5C=CH2
2 '
b$
191
Rulll!lb P I I
OH 2 1
Csb5c=CLIz
*
Pu(Il~b'Pl11
/'dl
C C6h,CCH3
1151
reaction steps is not known, and modification of some of the suggested reaction steps may later prove necessary. The general mechanism proposed bears a clear resemblance to that proposed for nucleophilic substitution at (tertiary) carbon in electron-deficient benzyl halides or for certain examples of aromatic nucleophilic ~ u b s t i t u t i o n . ~ ~ (28) For a recent summary of the literature on electron-transfer reactions of the excited state of Ru"(bpy)Y and other inorganic complexes, see: (a) R. C. Young, J. K. Nagle, T. J. Meyer, and D. G. Whitten, J . Am. Chem. Soc., 100, 4773 (1978); (b) P. J. DeLaive, J. T. Lee, H. W. Sprintschink, H. Abruiia, T. J. Meyer, and D. G. Whitten, ibid.,99, 7094 (1977). (29) In the absence of dye the dihydropyridine must be the light absorber. The excited state of dihydropyridine could either transfer electronic energy or an electron to 3b to initiate the reaction. (30) J. F. Bunnett, Acc. Chem. Res., 11, 414 (1978).
Hydride Transfer from 1,4-Dihydropyridines
J . Org. Chem., Vol. 44, N o . 26, 1979 4959
In eq 7-15 steps involving chain character have not been included. Chain character is readily realized if 23- abstracts a proton from 2a rather than from Ru"(bpy),H2+ (step 14); this produces acetophenone and radical 21., which can participate again in step 12, leading to chain character. Reliable quantum-yield measurements supported b y isotopic-labeling studies are needed to verify whether the reaction has chain character. Note also that at this time the postulation of hydrogen a t o m transfer steps, as opposed to electron-transfer steps, is entirely heuristic. Again more information is needed to make a distinction between
Dimethylphenacylsulfonium perchlorate (3a) was prepared by stirring a solution of 8.5 g (0.042 mol) of phenacyl bromide and 5.0 g (6 mL, 0.08 mol) of dimethyl sulfide in 50 mL of benzene for 24 h. The precipitated sulfonium bromide37was collected by filtration and was dissolved in 100 mL of H20. The solution was filtered, a saturated aqueous sodium perchlorate solution was added, and 6.0 g (0.021 mol, 50% yield) of 3a was collected by filtration: mp 185-187 "C (recrystallized from ethanol/acetonitrile); IR (KBr) 1680 (C=O), 1080 cm-' (ClO,); 'H NMR (C3DsO) 6 3.20 (s, 6 H, 2 CH3), 5.58 (s, 2 H, CHJ, 7.50-8.25 (m, 5 H, aryl H). Anal. Calcd for CloH,3C10jS: C, 42.79; H, 4.67; C1, 12.63. Found: C, 42.84; H, 4.60; C1, 12.60. these two possibilities. Methylphenacylphenylsulfonium tetrafluoroborate (3b) was prepared by adding 8.8 g (0.042 mol) of silver tetrafluoroborate Conclusions portionwise to a well-stirred solution of 8.5 g (0.042 mol) of phenThe reductions of various electron-deficient sulfonium acyl bromide and 8.7 g (0.070 mol) of thioanisole in 75 mL of salts and alkyl halides by 1,4-dihydropyridines can be rapid methylene chloride. Stirring a t ambient temperature was continued for 20 h, and the insoluble salts were removed by filtration. and quantitative when carried out under the proper conThe filtrate was evaporated, and the residue was crystallized by ditions, i.e., ambient or lower t e m p e r a t u r e and initiation stirring it with 25 mL of acetonitrile, giving 11.6 g (0.034 mol, 83% by visible light with added sensitizers. T h e competing yield) of 3b: mp 120-122 "C (recrystallized from absolute reactions of alkylation of an enamine carbon of the diCzHjOH); IR (KBr) 1680 (C=O), 1050 cm-' (BF4-); 'H NMR hydropyridine and isomerization of the dihydropyridine (C3DsO)6 3.56 (5, 3 H, CH3), 5.96 (s, 2 H, CH2),7.50-8.50 (m, 10 are suppressed under these conditions. H, aryl H). Some questions remain unanswered. One-electron Anal. Calcd for C1&11J3F40S: C, 54.57; H, 4.58 S, 9.71. Found pathways account for many of the reductions, but the exact C, 54.59; H, 4.57; S, 9.67. sequence of steps is a matter of speculation at this time. (4-Methoxyphenacy1)diphenylsulfonium tetrafluoroIt is not known whether the mechanism for alkylation is borate (3c) was prepared by adding a mixture of 4-methoxyphenacyl bromide (14.0 g, 0.061 mol) and diphenyl sulfide (27 g, related t o or i n d e p e n d e n t of the reduction mechanisms. 0.145 mol) over 30 min to AgBF, (0.057 mol) in 50 mL of methIt is also unclear whether all reductions are one-electronylene chloride. The reaction mixture was allowed to stir another transfer processes. It will be difficult to o b t a i n answers 12 h, the AgBr was removed by filtration, and the solvent was to these questions.6-f removed to leave a heavy oil, which was taken up in 100 mL of We d o feel that our results, at this stage chiefly dediethyl ether. Two layers were formed: the lower gray-brown scriptive, expand significantly the scope and mechanistic layer was separated and was dissolved in a warm petroleum ether knowledge of reductions b y 1,4-dihydropyridines. S u c h (4MO "C)/benzene (1:l)mixture, and the insoluble material was information aids in the design of new synthetic systems31 filtered off. On cooling (11 g, 0.0261 mol, 46% yield) of the and providing essential information for the mechanisms sulfonium salt 3c precipitated as white crystals: mp 132-133 "C; 'H NMR (CD3COCD3)6 3.95 (s, 3 H, CH30),6.50 (9, 2 H, CHJ, of NAD(P)H-catalyzl.d reduction^.^^ 7.0-8.3 (complex, 8 H, aromatic). Anal. Calcd for C20H19BF402S:C, 59.76; H, 4.54; S, 7.59; F, Experimental Section 17.99. Found: C, 59.87; H, 4.54; S, 7.63; F, 17.87. Melting points were determined either on a melting point block (4-Methoxyphenacyl)methylphenylsulfonium tetraor on an automatic Metiler apparatus and were not corrected in fluoroborate (3d) was prepared from AgBF, (6.0 g, 0.031 mol), either case. Spectral measurements were made on usual laboratory 4-methoxyphenacyl bromide (7.1 g, 0.031 mol), and thioanisole instruments. Compounds cited without reference were either (9.0 g, 0.073 mol) as described above. There was obtained 10.0 commercially available or were prepared by literature methods. g (0.0278 mol, 90% yield) of 3d: mp 140-141 "C; 'H NMR Fluorescence quenching experiments were done on samples de(CDBCOCDJ 6 3.53 (s, 3 H, CH3), 3.90 (s, 3 H, CHSO), 5.87 (s, gassed by five freeze-t haw cycles. All dihydropyridines and 2 H, CHJ, 6.9-8.3 (complex, 9 H, aromatic). sulfonium salts were carefully stored in the dark to avoid deAnal. Calcd for Cl6HI7BF4O2S:C, 53.65; H, 4.76; S, 8.91; F, composition. 21.10. Found: C, 53.23; H, 4.81; S, 8.88; F, 20.85. 1,2,6-Trimethyl-3,5-bis(ethoxycarbonyl)l,4-dihydro(3-Methoxyphenacyl)methylphenylsulfonium tetrapyridine (2a) was prepared from 1,2,6-trimethyl-3,5-bis(ethfluoroborate (3e) was prepared from AgBF, (4 g, 0.0205 mol), oxycarbony1)pyridinium ~ e r c h l o r a t eby~ ~ following a literature 3-methoxyphenacyl bromide (4.7 g, 0.205 mol), and thioanisole procedure.34 A similar procedure was followed for the preparation (7.5 g, 0.06 mol). There was obtained 4.3 g (0.012 mol, 58% yield) of 2b. of 3e: mp 119.5-120 "C; 'H NMR (CD3COCD3)6 3.54 (s, 3 H, 1,2,6-Trimethyl-3,5-bis(ethoxycarbonyl)-1,2-dihydroCH3S),3.83 (s, 3 H, CH30),5.95 (s, 2 H, CH?),7.3-8.4 (complex, pyridine (5) was prepared by following a literature procedure.33 9 H, aromatic). l-Benzyl-1,4-dihydronicotinamide (1) was prepared from Anal. Calcd for CI6Hl7BF4O2S:C, 53.26; H, 4.76; S, 8.91; F, 1-benzylnicotinium chloride3' as described in the l i t e r a t ~ r e . ~ ~ 21.10. Found: C, 53.39; H, 4.74; S, 8.93; F, 21.25. (2-Methoxyphenacy1)met hylphenylsulfonium tetrafluoroborate (3f) was prepared from AgBF, (2.5 g, 0.013 mol), (31) J. G. de Vries and 12. M. Kellogg, J . Am. Chem. SOC.,101, 2759 2-methoxyphenacyl bromide (2.94 g, 0.13 mol), and thioanisole (1979). (5 g, 0.04 mol). There was obtained 2.8 g (0.008 mol, 61% yield) (32) For a discussion of' one-electron-transfer mechanisms in biochemical systems, see: (a) R. F. Williams, S.Shinkai, and T. C. Bruice, of 3f mp 144.5-145 "C; 'H NMR (CD3COCD3)6 3.52 (s, 3 H, Proc. Natl. Acad. Sei. U.S.A., 72, 1763 (1975); (b) T. C. Bruice and Y. CH30),4.03 (s, 3 H, CH,O), 5.82 (s, 2 H, CHL),6.9-8.4 (complex, Yano, J . Am. Chem. SOC.,9'7, 5263 (1975); (cj T. C. Bruice, Prog. Eioorg. 9 H, aromatic). Chem. 4, 1 (1976). (d) See also G. N. Schrauzer and J. W. Sibert, Arch. Anal. Calcd for CI6Hl7BF4O2S:C, 53.36. H, 4.76; S, 8.91; F, Aiochim. Biophys., 130, 257 (1969),for a description of related reactions 21.10. Found: C, 53.28; H, 4.82; S, 9.01; F, 21.31. involving vitamin E!l2. (4-Nitrophenacyl)methylphenylsulfoniumtetrafluoro(33) T. J. van Bergen amd R. M. Kellogg, J . Am. Chem. Soc., 94, 8451 (1972). borate (3g) was prepared as described above from AgBF, (4.0 (34) A. F. E. Sims and P. W. G. Smith, h o c . Chem. Soc., London, 282 g, 0.0205 mol), 4-nitrophenacyl bromide (5.0 g. 0.0206 mol), and (1958). (35) P. Karrer and F. J. Stare, Heic. Chim. Acta, 20, 418 (1937). (36)D. Mauzerall and F. H. Westheimer, J . A m . Chem. SOC.,77, 2261 (1955).
( 3 7 ) A. J. Speziale, C. C. Tung, K. W. Ratts, and A. Yao. J . Am. Chem. Soc., 87, 3460 (1965).
4960 J . Org. Chem., Vol. 44, No. 26, 1979 thioanisole (7.5 g, 0.06 mol). The AgBr and the sulfonium salt were isolated from CH2C1, by filtration with a P4 glass filter, and the precipitate was taken up in warm CH30H. The AgBr was removed by filtration. When the CH,OH solution was cooled, the sulfonium salt separated. After several recrystallizations there was obtained 2.5 g (0.0067 mol, 32% yield) of product: mp 180-181.5 "C; 'H NMli (CD3COCD3) 6 3.58 (s, 3 H, CH3), 6.06 (s, 2 H, CHJ, 7.5-8.4 (complex, 9 H, aromatic). Anal. Calcd for C15H14BF4N03S:C, 48.02; H, 3.76; N, 3.74; F, 20.25. Found: C, 48.12; H, 3.74; N, 3.82; F, 20.40. (3-Nitrophenacyl)methylphenylsulfoniumtetrafluoroborate (3h) was prepared from AgBF4 (2.25 g, 0.011 mol), 3nitrophenacyl bromide (2.8 g, 0.011 mol), and thioanisole (4.5 g, 0.038 mol). There waij obtained 3.2 g (0.0086 mol, 86% yield) of 3h: mp 123.5125 "C; 'H NMR (CD3COCD3)d 3.61 (s, 3 H, CH,S), 6.06 (s, 2 H, CH2), 7.6-8.6 (complex, 9 H, aromatic). Anal. Calcd for CI5tl4BF4NO3S:C, 48.02; H, 3.76; N, 3.74. Found: C, 48.0'2; H, 3. (1;N, 3.83. (2-Nitrophenacyl)methylphenylsulfoniumtetrafluoroborate (3i) was prepared from AgBF4 (1.3 g, 0.0065 mol), 2nitrophenacyl bromide (1.6 g, 0.0065 mol), and thioanisole (2.5 g, 0.02 mol). Isolation was complicated by the precipitation of the sulfonium salt with AgBr. The combined precipitate was taken up in CH30H, the AgBr was filtered off, and the salt 3i, was allowed to crystallize out. The material in the CH2C12filtrate was isolated by removal of CH2C12,addition of 50 mL of (C2H5)?0, removal of the heavy brown insoluble oil, and recrystallization of this material from CH30H. The samples of 3i were combined and recrystallized several times from CH30H to give 0.7 g (0.0021 mol, 33% yield) of 3i: mp 171&172.5 "C; 'H NMR (CD3COCD,) 6 3.25 (s, 3 H, CH3S),5.16 (s, 2 H, CH2),7.45-8.3 (complex, 9 H, aromatic). Anal. Calcd for C15H,,BF4N03S: C, 48.62; H, 3.76; N, 3.75. Found: C, 47.65; H, 3.67; N, 3.78. Methyldiphenylsulfonium perchlorate (3k) was prepared by adding dropwise a solution of 6.84 g (0.06 mol) of methyl fluorosulfonate in 30 mL of methylene chloride to a stirred and ice-cooled solution of 11.16 g (0.06 mol) of diphenyl sulfide also in 30 mL of the same solvent. After a 16-h reaction time the solvent was evaporated, and the residue was dissolved in 50 mL of water. A solution of 70% aqueous perchloric acid was added dropwise until all the 3k had precipitated. Filtration followed by recrystallization from 90 mL of a 1:l methanol/ethanol mixture afforded 8.29 g (0.03 mol, 4570 yield) of 3k: mp 69.5-73 "C (lit.38 mp 73-74 "C); 'H NMR (CD30D)6 3.88 (s, 3 H, CHJ, 7.90-8.50 (m, 10 H, aryl HI. Benzyldimethylsulfonium tetrafluoroborate (31) was prepared by adding 11.3 g (0.058 mol) of silver tetrafluoroborate portionwise to a well-stirred and ice-cooled solution of benzyl bromide (10 g, 0.058 mol) and dimethyl sulfide (6 mL, 0.08 mol) in 50 mL of methylene chloride. After a 16-h reaction period, followed by filtration and evaporation, a residue was obtained that was recrystallized from 2-propanol to yield 8.6 g (0.036 mol, 62% yield) of 31: mp 99-101 "C; 'H NMR (CD30D)6 2.78 ( s , 6 H, 2 CH3), 4.58 (s, 2 H, CHJ. 7.46 (s, 5 H, aryl H). Anal. Calcd for CSH13BF4S:C, 45.02: H, 5.46; S, 13 C, 45.27; H, 5.42; S, 13.37. Benzylmethylphenylsulfonium tetrafluoroborate (3m) was prepared by adding silver tetrafluoroborate (8.8 g, 0.042 mol) portionwise to mastirred, ice-cooled mixture of excess benzyl bromide (30 g, 0.174 mol) and thioanisole (10.02 g, 0.042 mol). After a 20-h reaction period 50 mL of methylene chloride was added, followed by filtration and evaporation, giving a residue that solidified 011 stirring with 100 mL of ether. Filtration gave 7.7 g (0.025 mol, 60% yield) of 3m: mp 121-122 "C (recrystallized from ether/acetonitrilt); 'H NMR (C3DsO)6 3.12 (s, 3 H, CH3), 4.98 and 5.26 (d,J = 1Hz, 2 H, CH,), 7.35 (s, 5 H, aryl H). 7.60-8.10 (m, 5 H, aryl H). Anal. Calcd for Cl4H1,,BF,S:C, 55.65: H, 5.00; S.10.61. Found: C, 55.62; H, 5.12; S, 10.68. Benzyldiphenylsulfonium tetrafluoroborate (3n) was prepared from diphenyl sulfide (10.2 g, 0.054 mol), excess benzyl (38) V. Franzeri. H. .J. Schmidt. and C . Mertz. C'hem. Her., 91. 2942 (1961).
van Bergen e t al. bromide (50 g), and silver tetrafluoroborate (10.5 g, 0.054 mol) via a literature procedure.3a There was obtained 7.3 g (0.020 mol, 37% yield) of 3n, mp 105-108 "C (lit.38mp 105-106 "C). Benzylphenacylphenylsulfonium perchlorate was prepared from phenacyl phenyl sulfide (4 g, 17.5 mol), benzyl bromide (3.1 g, 18.2 mol), and AgC10, (3.7 g, 17.8 mmol) in 25 mL of CH& The yellow precipitate was filtered off and washed with CH2C12. The combined CH,C12 solutions were evaporated, the solid residue was dissolved in 50 mL of CH2Cl2(rvacuum as a “ c ~ l u m n ” .This ~ ~ ~afforded resolution comparable to that of gravity column chromatography (70-230 mesh sorbent) but in a much shorter time period. The major drawbacks to this very simple system were channeling, caused by the necessary intermittent breaking of the vacuum, uneven sample application, and limited resolution due to the shortness of the column. VLC overcomes these drawbacks. Channeling was eliminated by developing a system in which the column was kept under vacuum continuously. Sample application problems were overcome by (a) decreasing the ratio of column cross section to the quantity of the sorbent (use of a longer. narrower column) and (b) by the use of a preabsorbent layer of celite such as that used on some TLC plates. Resolution was increased greatly by an increase in column length relative to crosssectional ares. $Department ofCht,mistry. *Department of Oceanography 0022-3263/79/1944-4962$01.00/0
TRAPS A
MANIFOLD
4! Lr V A C U U M SOURCE
Figure 1. VLC apparatus and some specifications: A, stopcock/stopper; B, solvent reservoir (2 L); C, column; C,! preabsorbent layer (diatomaceous earth, celite, filter aid or equivalent); C1, sorbent (TLC grade, 10-40 Fm); D, sintered glass frit (10-20 pm pore size); E, eluent reservoir (250 mL); F, column isolation stopcock; G, vacuum/atmosphere stopcock; H, receiver head; trap 1, 250 mL; trap 2, 50 mL; vacuum, mechanical pump.
The apparatus shown in Figure 1 consists of the column C fitted with standard taper joints at upper and lower ends G. A. Fischer and J. J. Kabara, Anal. Biochem., 9 303 (1964). W. C. Still, M. Kahn, and A. Mitra, J . Orp. Chern., 43, 2923 (1978). W. H. Pirkle and R. W. Anderson, J . Org. Chern., 39, 3901 (1974). B. Loev and M. Goodman, Chern. Ind. (London),2026 (1967). B. F. Bowden, J. C. Coll, S. J. Mitchell, and G. J. Stokie, Aust. J .
Chern., 31, 1303 (1978). (6) J. C. Coll, S. J. Mitchell, and G. J. Stokie. Aust. J . Chern., 30, 1859 (1977).
C 1979 American Chemical Societv
