4156
BUNNETT A N D GLOOR
J . Org. Chem., VoE. 38, No. 24, 1973
S m l Phenylation of Nitrile Carbanions, and Ensuing Reactions. A New Route to Alkylbenzenes1i2 J. F. BUNNETT*AND BERNHARD F. GLOOR~ University of California, Santa Cruz, California 95064 Received June 25, 1973 Under stimulation by solvated electrons, the anions of aliphatic nitriles react with halobenzenes, phenyl diethyl phosphate, or phenyltrimethylammonium ion to form the a-phenyl derivative of the nitrile, the alkylbenzene that would result from decyanation thereof, and a benzylic radical dimer (e.g., l12-diphenylethane when the cyanomethyl anion is used), as well as minor products. In the postulated mechanism, a phenyl radical combines with the nitrile anion t o form the radical anion of an or-phenyl nitrile. The latter may lose an electron to appear as the nitrile, or it may expel cyanide ion forming a benzylic radical which dimerizes or is reduced to an alkylbenzene. The reaction has potential value in synthesis for the purpose of installing an alkyl group on an aromatic ring in place of a nucleofugic substituent or an amino or hydroxy group.
Aryl mcliculs are intermediates in the recently recognized S R N l mechanism of aromatic nucleophilic substitution.* $upply of an electron to a substituted benzene, in which the substituent is a halogen or other suitable leaving group, forms a radical anion which then ejects the nucleofugic substituent, emerging as an aryl radical. The radical combines with a nucleophile to form a new radical anion which, upon getting rid of a surplus electron, becomes a stable nucleophilic substitution product. An alkali metal dissolved in liquid ammonia exists for the most part as alkali metal cations and solvated electrons,j and is effective in provoking SRNl reactions. Among the nucleophiles successfully involved in substitutions by this mechanism are the amide ketone enolate ion^,^^^ and hydrocarbon-derived carbanions such as the fluorenide ion.lO Heretofore, aromatic S m l reactions involving acyanocarbanion nucleophiles have received only preliminary attention. Kim and Bunnett6 observed chlorobenzene to react with the cyanomethyl anion and potassium metal in liquid ammonia t o form phenylacetonitrile, toluene, benzene, and aniline. Rossi" conducted a similar experiment, with iodobenzene instead of chlorobenzene, and obtained a substantial amount of l,2-diphenylethane (DPE)I2as m l l as the other products mentioned. We now report a study of several reactions of this general type, involving six monosubstituted benzenes and the carbanions from seven aliphatic nitriles. The results are of interest to preparative chemistry. Also, they illuminate significant features of the reaction mechanism. Most of our observations conform to the generalized scheme of eq 1.
(1) Research supported in part by the National Science Foundation. (2) Presented in part a t the 164th National Meeting of the American Chemical Society, New York, Irj. Y., Sept 1972, Abstract O R G N 45. (3) Grateful recipient of a fellowship, 1971-1972, from the Schweizerisohe Stiftung far Stipendien auf dem Gebiete der Chemie. (4) J. K. Kim and J.F. Bunnett, J . Amer. Chem. Soe., 92, 7463 (1970). ( 5 ) J. L. Dye, Accounts Chem. Res., 1, 306 (1968). ( 6 ) J. K. Kim and J. F. Bunnett, J . Amer. Chem. Soc., 92, 7464 (1970). (7) R. A. Rossi and J. F. Bunnett, J . Orq. Chem., 37, 3570 (1972). ( 8 ) R . 4 . Rossi and J. F. Bunnett, J . Amer. Chem. Soc., 94, 683 (1972). (9) R . A. Rossi and J. F. Bunnett, J. O w . Chem., 38, 1407 (1973). (10) R . A. Rossi and J. F. Bunnett, J . O w . Chem., 38, 3020 (1973). (11) R. A. Rossi, unpublished work. (12) Glossary of acronyms: B M E , benzyl methyl ether; D P E , 1,Z-diphenylethane; D P M , diphenylmethane; M P A N , 3-methylphenylaoetonitrile; IVIPAN-, anion of M P A K ; PAN, phenylacetonitrile; P B K , aphenylbutyronitrile.
Phx
+ RCHI
K++ K PhCHR
CN Ph2CHR
+ PhCHzR +
1
h"s
CN
+ PhCH-CHPh + C6H6 4- CaI-kNHz RI
RI
(1)
Results Our two principal series of experiments are summarized in Tables I and 11. Table I concerns several experiments involving the cyanomethyl anion, from reaction of acetonitrile with an equimolar amount of KSH2. The several runs differ in the identity of the monosubstituted benzene employed, in the temperature, in the proportions of reactants, and in the method for conducting the experiment. I n some runs, solvated electrons (from the dissolved potassium metalb) were constantly in large excess over the aromatic substrate, while in others the concentration of solvated electrons was kept quite low. The products obtained from reactions with cyanomethyl anion (eq 1, R = H) are those described by earlier workers, as mentioned, plus a small amount of diphenylmethane (DPAI) .l 2 Toluene is prominently formed, in yields ranging from 14 to 49%. Benzene is also prominent, in yields from 8 to 44%. D P E is formed in considerable amount in some runs but to a minor extent in others; yields vary from 3 to 40%. The same can be said for phenylacetonitrile (PAX), the yields of which are from 2 to 31%. The highest yield of D P N encountered was 7%, and in some runs only trace amounts were formed. Aniline yields are also very small. Despite the considerable differences in conditions and in results among the several runs of Table I, it is difficult to correlate product patterns with experimental variables. It should be noted that our procedures for the addition of potassium metal and/or aromatic substrate during the course of a run were not such as t o provide close control of addition rates or of solvated electron concentration in the reaction mixture. I n consequence, there may have been substantial variation of the concentration of solvated electrons and/or of reaction intermediates, even between runs ostensibly conducted by the same technique. For exceedingly fast reactions, as these are, such variation plausibly would have a significant effect on product proportions. The experiments of Table I1 concern carbanions derived from other nitriles. Again there is substantial variation of product patterns between runs, and again
J . Org. Chem., Vol. 38, No. 24, 1973 4157
SRK1 PHENYLATION OF NITRILE CARBANIONS
TABLE I
------
REACTIONS OF MONOSUBSTITUTED BENZENES WITH CYANOMETHYL ANIONS,PROVOKED BY POTASSIUM METALIN LIQUIDAMMONIA Run no. Registry no. 1 462-06-6 2 3 4 108-90-7 5
F F F C1
c1 c1 c1
6
7 8 9 10 11 12 13 14 15 16
Substituent
c1
108-86-1 591-50-4 2510-86-3 98-04-4
c1 c1 C1 c1 Br
I OPO(0Et)z
N(CHa)a-I-
P h X , CHzCNK. mmol mmol 25 115 14 76 40 123 22 87 60 150 64 160 63 75 165 165 67 80 30 88 64 80 146 49 27 106 25 95 50 80 63 78
K , mmol 63 40 107 55 69 95 110 330 81 37 (15)* 87 (34)' 254 (85)" 69 64 90 (2Qr 85
Temp, Ether, Methoda ml Toluene PAN' OC 80 44 2 -33 Af 65 30 3 Ab' -33 AB! 49 3 -78 -33 Ak 70 40 7 31 -33 A' 18 24 B 24 -33 19 -33 B 16 19 -78 B 14 18 B 31 -78 27 12 -78 B -78 AB 35 22 -33 AB 46 3 -33 B 70 26 5 -33 B 70 14 5 -78 AB 43 3 -78 ABt 26 5
ml
"3,
150 110 250% 130 50 50 50 50 50 60 60 (150) 50 (250) 150 150 50 50
Yield, %-------
D P W e D P E d e CeHs Aniline Trace 8 31 -1 0 7 3 44 h 4 2
23 10 12 20 5 17 9 17 3 2 7 5 30 14 26 40 8 12 18 7 22* 14 43 25 32 7 11 19 21
-2 -3 5 3
5 2 7 3 3 4 1 4
2 -2 m m
m m
lop
-1 m
-38 -7
Methods: A, the monosubstituted benzene, neat or in solution, was slowly added to a solution of CH2CNK and K metal; AB, the monosubstituted benzene, neat or in solution, was slowly added to a solution of CHZCSK,and K metal was added slowly in small portions so as t o keep K metal in more or less constant excess; B, to a solution of CHzCSK and the monosubstituted benzene, a small DPM piece of K metal was added and then, after the blue color had vanished, another small piece, etc. PAN = phenylacetonitrile. = diphenylmethane. DPE = IJ2-diphenylethane. 6 The yield calculation takes account of the fact that 2 mol of C&X are required to form 1 mol of DPM or DPE. f C&F in ether (5 ml) added during 30 min; quenched with CeHjCOO?u'a,then NHaC1. 0 CsH& in ether (40 ml) added. la Not sought. S o t distilled before use. 3 C&sF in SH3 (150 ml) added during 90 min; quenched C6HsCl added as fast as possible (during 5 min); k CsH&l in ether (5 ml) added during 40 min. with C6H;COONaJ then "$1. vigorous refluxing. m A tiny peak at the retention time for aniline. fi After addition of 37 mmol of K in especially small pieces, ice was added until the orange color faded, and then a further 15 mmol of K. 0 Half the C6H;Cl was added, then about 44 mmol of K, then the rest of the C&&l, then about 43 mmol of K, then 390 mmol of ice (causing the orange color to fade), then 34 mmol of K . p After addition of 254 mmol of K, 670 mmol of ice and 200 ml of ammonia were added, and then 85 mmol of K (with shaking of the 8 47, of phenol also thick slurry). Based on C&Cl. r After addition of 90 mmol of K, ice was added and then 25 mmol of K. obtained. K added in two portions, each followed by half the substrate. a
11 REACTIONS OF MONOSUBSTITUTED BENZENES WITH ANIONS FROM NITRILES OF STRUCTURE KCHzCS, PROVOKED BY POTASSIUM AIETAL I N LIQUIDAMMONIA TSBLE
7 Yield, %---------
Run no. 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
[RCHC N - - l , [C6H5X1, R CHa CHa CHs CHa CtHs CiHa C2H5 CzHs (CH3)Z0 n-CsHi n-CaH7 (CHa)zCH (CHdzCH (CHa)zCH (CHdzCH CsHs C6H5
X of CeH6X c1 c1 OPO(0Et)r N( CHa)3I' -
F c1
Registry no. 42117-12-4
42117-13-5
I OPO(0Et)z Br C1 OPO(0Et)Z C1 OPO(0Et)z
42117-14-6 42117-15-7 42117-16-8
OPO(0Et)z OPO(0Et)z OPO(0Et)z N(CHs)a+I-
18802-89-6
IM
1M
1.38 1.40 1.16 1.07 1.28 1.37 0.30 1.04 0.98 1.09 1.58 1.64 1.80 1.30 0.63 1.44 1.50
0.87 2.80 0.73 0.67 0.43 4.1 0.16 0.15 2.94 3.30 0.60 3.2 0.72 0.52 0.20 1.12 1.19
K, M' 2 . 0 (0.65) 3.98 1 . 7 (0.1)v 1.26 1.09 6.04 0.20 0.30 5.3 6 . 3 (1.7) 1 . 4 5 (0.2) 4.9 1.48 0 . 8 5 (0.23) 0.70 1.47 2.08
Ph- PhCHTemp, 'C Methoda CHzR R C N -78 -4B 22 d -33 AB 34 6 -78 AB 14 d -78 ABi 8 d -78 ABi 28 4 -33 ABk 37 0.5 -33 A 6 29 -33 B 28 4 -33 AB 27 -33 AB 56 d -33 BAP 38 10 -33 AB 37 19' -78 B 20 7 -33 BAP 31 10 -78 ABi 22 15 -78 AB 12 3t -78 AB 17
PhPhz- ,--CHCRHRPhCCHR Meso Rae d 5 5 3 6 6 7 d 7 7 d 8 8 3 d 13 13 13 2 12 12 0.2 1 1 m
m
d 12
d
d d 6 12
d d
m
d
2
d
d
d d
3 4
CsH6 Aniline 4 5 3Se loe,' 35 5h 6 3 35 13 278 3' 27 1 20 n 31 7 38' 14' 7 q 31e -5' 36 -2' 2 d 1 2 25 1" 43 18
a See footnote a,Table 1. Concentration that would have prevailed had there been no reaction; the K indicated in parentheses was added after ice. The glpc peaks for racemic and meso stereoisomers were not fully resolved, but were approximately equal in A tiny area; the sum of the two could be measured accurately, and was arbitrarily allocated in equal parts to meso and racemic. peak at the expected retention time. e Based on CaH6Cl. f 4% of CsHsC1 recovered. b' The K indicated in parentheses was added after ice and 1.50ml of ether. Phenol (2%) also formed. Excess K present. a t the end was destroyed by addition of ice. j The CaF& in I50 ml of "I, was added during 90 min. After reaction, S H 3was added to increase the volume from ca. 50 ml to 200 ml, followed by 10 g of ice and 75 mmol of K. 12% of CsHJ recovered. m Detected qualitatively. fi Phenol (29%) and some 4-amino-3-cyano-3heptene also formed. Isobutyronitrile. p Method BA: the C&jX and K metal were both added in portions, but so as always to keep Cs&X in excess. Phenol (8%) also formed. I^ After decyanation of the isolated product mixture, 507, of isobutylbenzene and a mere trace of 2-phenyl-3-methylbutanonitrile were obtained. Phenol (6%) also formed. Identification solely by glpc retention time. Phenol (12%) also formed; 80% of P A S recovered. 76% of P A S recovered.
the variation is often diEcult to correlate with differences in reaction participants or conditions. Alkylbenzenes, PhCH2R, corresponding to toluene in Table I, are prominent products of most runs, as is benzene. Phenyl derivatives of the starting nitriles are formed in significant amounts in some runs but only in trace amounts in others. l,l-Diphenylalkanes, Ph&HR, appear to a significant extent in only a few runs, most
of which involve the aromatic substrate in excess. Dimeric products, meso and racemic PhCHRCHRPh, are formed in amounts totalling as high as 26% in reactions of the anions from propio- and butyronitrile, but only in minor amounts in the other runs. The yields of aniline are variable, but never large. Photostimulated Reactions. -Inasmuch as S R N ~ reactions of halobenzenes with acetone enolate ion
4158 J . Org. Chem., Vol. 58,No. 24, 1975
BUNNETT AND GLOOR TABLE
111
REACTIONS OF BROMOBENZENE WITH CYASOMETHYL ANIOS,A N D REACTIONS WITH MIXEDCYANOMETHYL A N D ACETOSE ENOLATE IONS, IS LIQUID AMMOSIAAT -33"
--.
yo
'-------Yield, --
Run no.
[CsHsBr], M
[KNH21,
.Ma
[CHaCNI, Ma
[Acetonel,
.IfQ
Reaction time, min
Promoter
CsHsBrb
C6He
Toluene
PAN
DPM
DPE
Phenylacetone
34 0.08 0.46 0.46 120 Dark 98 1 35 0.08 0.52 0.54 120 hv 62 1 2 8 1 18 36 0.07 0.74 0.68 0.07 125 hv 44 3 2 14 1 36
