Alkylation of Acetonitrile

Full text of DOI:10.1021/jo971198h

J . Org. Chem. 1997, 62, 8575-8576
8575
Ta ble 1
Alk yla tion of Aceton itr ile
Douglass F. Taber* and Sue Kong
Department of Chemistry and Biochemistry, University of
Delaware, Newark, Delaware 19716
Received J uly 1, 1997
1
We recently needed to homologate bromide 1 to nitrile
2
. Although multistep procedures for effecting this
2
transformation have been established, the straightfor-
ward alkylation of lithioacetonitrile had not been opti-
mized.3 We now report that this direct alkylation can
in fact be effected in reasonable yield.
,4
a
Yields are for isolated products. b Only 1 equiv of lithioaceto-
nitrile was used. The yield is based on starting material not
recovered (conversion was 50%).
The inherent difficulty with this alkylation is that the
product (e.g., 2) is more acidic than acetonitrile. Once
the alkylation has proceeded to partial conversion, the
acetonitrile anion can act either as a nucleophile, to
convert the alkylating agent to the product, or as a base,
to deprotonate the product that has already been formed.
The anion resulting from the latter process then reacts
with the alkylating agent to give the dialkylated nitrile.
To solve this problem, we have developed two experi-
mental protocols (Table 1). In procedure A, we add the
alkylating agent all at once to an excess of lithioaceto-
nitrile (prepared by the addition of n-BuLi in hexane to
acetonitrile in THF at -78 °C) at low temperature. In
procedure B, we add lithioacetonitrile slowly, via cannula,
to the alkylating agent at 0 °C. While both protocols are
effective, procedure B works for a broader range of
alkylating agents. With both procedures, the major
competing side reaction is dialkylation.
and concentrated, and the residue was chromatographed to give
2
f
as a colorless oil (3.12 g, 50% yield): TLC R (5% MTBE/
-1
petroleum ether) ) 0.33; IR (film) 2937, 2246, 1607, 1451 cm
;
1
H NMR δ 6.74 (dd, 1/3H, J ) 10.7 Hz, 17.5 Hz), 6.36 (dd, 2/3H,
J ) 10.7 Hz, 17.5 Hz), 5.22 (m, 3H), 2.32 (m, 4H), 1.77 (m, 5H);
1
3
C NMR δ u 135.6, 134.0, 119.2, 114.1, 111.2, 26.5, 25.7, 25.2,
4.9, 16.1, 16.0 d 140.6, 132.7, 129.5, 127.6, 19.4, 11.3; MS m/z
2
(
(
1
rel inten) 135 (41), 134 (11), 120 (13), 107 (11), 106 (9.5), 95
39), 81 (100); exact mass calcd for C 13N 135.1048, found
35.1052.
P r ep a r a tion of tetr a d eca n en itr ile (4) (m eth od A): TLC
R (5% MTBE/petroleum ether) ) 0.30; bp (bath) ) 100-
9
H
f
0.5mm
-
1 1
110 °C; IR (film) 2924, 2854, 2246, 1466 cm ; H NMR δ 2.33
(
1
3
t, 2H, J ) 7.1 Hz), 1.64 (pentet, 2H, J ) 7.2 Hz), 1.44 (m, 2H),
.26 (bs, 18H), 0.88 (t, 3H, J ) 6.6 Hz); 13C NMR δ u 119.7,
1.8, 29.5, 29.4, 29.2, 28.7, 28.6, 25.3, 22.6, 17.0 d 14.0; MS m/z
(rel inten) 194 (0.95), 180 (14), 166 (26), 152 (22), 138 (26), 125
(
11), 124 (50), 111 (41), 110 (76), 97 (100); exact mass calcd for
+
We believe that this direct alkylation of lithioacetoni-
trile will be a useful addition to the armamentarium of
organic synthesis.
C14H28
N
(M + 1) 210.2222, found 210.2227.
P r ep a r a tion of Dod eca n en itr ile (6) (Meth od B). A solu-
tion of acetonitrile (0.26 mL, 5.0 mmol) in 6.5 mL of dry THF
was added to n-BuLi (2.25 mL, 2.40 M in hexanes) at -78 °C
under N . The mixture was stirred at -78 °C for 1 h and then
2
Exp er im en ta l Section 5
transferred by cannula to a solution of benzenesulfonate 5 (597
mg, 2.00 mmol) in 2.5 mL of dry THF at 0 °C over 20 min. The
mixture was stirred for an additional 15 min and then was
quenched with 10 mL of water. The mixture was partitioned
between 50% MTBE/petroleum ether and saturated brine. The
P r epar ation of 6-Meth yl-5,7-octadien en itr ile (2) (Meth od
A). A solution of acetonitrile (6.00 mL, 115 mmol) in 140 mL of
dry THF was added to n-BuLi (48.1 mL, 2.39 M in hexanes) at
-
2
78 °C under N . The mixture was stirred at -78 °C for 1 h,
combined organic extract was dried (Na
distilled bulb-to-bulb to give 8 as a colorless oil (261 mg, 72%
yield): bp (bath)0.5mm ) 80-90 °C; TLC R (10% MTBE/petroleum
ether) ) 0.55; IR (film) 2927, 2922, 2239, 1460 cm ; H NMR δ
2 4
SO ), concentrated, and
after which a solution of bromide 1 (8.07 g, 46.1 mmol) in 57
mL of dry THF was added all at once. The temperature was
kept at -78 °C for 1 h, and then 50 mL of water was added and
the mixture partitioned between 20% MTBE/petroleum ether
f
-
1 1
2
1
2
.33 (t, 2H, J ) 7.0 Hz), 1.62 (pentet, 2H, J ) 7.2 Hz), 1.40 (m,
6H), 0.88 (t, 3H, J ) 6.4 Hz); 13C NMR δ u 119.5, 31.7, 29.31,
9.28, 29.1 (2), 28.5, 28.4, 25.1, 22.4, 16.8 d 13.8; MS m/z (rel
2 4
and water. The combined organic extract was dried (Na SO )
(
1) J ulia, M.; J ulia, S.; Stalla-Bourdillon, B.; Descoins, C. Bull. Soc.
Chim. Fr. 1964, 2533.
2) For previous reports of the direct alkylation of acetonitrile, see:
a) Barrett, G. C.; Grattan, T. J . Tetrahedron Lett. 1979, 4237. (b)
inten) 182 (M + 1) (4.2), 180 (4.8), 152 (31), 138 (57), 125 (15),
24 (65), 111 (48), 110 (84), 98 (15), 97 (100); exact mass calcd
for C12 23N 181.1831, found 181.1842.
P r ep a r a t ion of 3-(4-br om op h en yl)p r op a n en it r ile (8)
m eth od A or B): TLC R (25% MTBE/petroleum ether) ) 0.30;
IR (film) 3027, 2936, 2246, 1592, 1488 cm ; H NMR δ 7.45 (d,
H, J ) 8.3 Hz), 7.10 (d, 2H, J ) 8.3 Hz), 2.90 (t, 2H, J ) 7.3
1
(
H
(
Larcheveque, M.; Mulot, P.; Cuvigny, T. J . Organomet. Chem 1973,
C33. (c) Horner, L.; Gusten, H. J ustus Liebigs Ann. Chem. 1962, 652,
(
f
9
1
1
9. (d) Savoia, D.; Trombini, C.; Umani-Ronchi, A. Tetrahedron Lett.
977, 653. (e) Zhou, S.-E.; Anne, S.; Vandewalle, M. Tetrahedron Lett.
996, 37, 7637.
-1 1
2
1
3
Hz), 2.59 (t, 2H, J ) 7.3 Hz); C NMR δ u 136.9, 121.0, 118.7,
30.8, 19.0 d 131.8, 129.9; MS m/z (rel inten) 211 (54), 209 (55),
171 (100), 169 (97), 129 (3.7), 128 (4.1), 103 (9.7), 102 (9.2); exact
(3) For a review of nitrile alkylations, see: Arseniyadis, S.; Kyler,
K. S; Watt, D. S. Organic Reactions; J ohn Wiley & Sons, Inc.: New
York, 1984; Vol. 31, p 1.
8
1
79
(4) (a) For the displacement of allylic and benzylic halides with the
mass calcd for C
08.9840, found 208.9826. Anal. Calcd for C
H, 3.84. Found: C, 51.47; H, 4.04.
H
N
Br 210.9819, found 210.9793, C
9 8
H N Br
9
8
organocopper derivative of acetonitrile, see: Corey, E. J .; Kuwajima,
I. Tetrahedron Lett. 1972, 487. (b) For the displacement of halides,
most efficiently allylic and benzylic, with the organozinc derivative of
acetonitrile, see: Orsini, F. Synthesis 1985, 500.
2
9 8
H
BrN: C, 51.46;
P r epar ation of (Z)-9-Meth yl-4-decen en itr ile (10) (Meth od
B). The (Z)-allylic chloride was prepared by the literature
(5) For general experimental procedures, see: Taber, D. F.; Meagley,
R. P.; Doren, D. J . J . Org. Chem. 1996, 61, 5723.
route:6 TLC R
f
(5% MTBE/petroleum ether) ) 0.33; bp (bath)0.5mm
S0022-3263(97)01198-5 CCC: $14.00 © 1997 American Chemical Society

8
576 J . Org. Chem., Vol. 62, No. 24, 1997
Notes
1
)
75-80 °C; IR (film) 2953, 2923, 2246, 1633, 1462 cm-1; H
(9.3), 230 (6.6), 204 (40), 202 (40), 191 (6.8), 190 (100), 189 (7.1),
7
9
+
NMR δ 5.56 (m, 1H), 5.36 (m, 1H), 2.37 (m, 4H), 2.03 (dd, 2H, J
7.3 Hz), 1.53 (m, 1H), 1.37 (m, 2H) 1.18 (m, 2H), 0.87 (d, 6H,
J ) 6.5 Hz); C NMR δ u 119.1, 38.3, 27.2, 27.0, 23.0, 17.2 d
33.3, 124.8, 27.6, 22.3 (2); MS m/z (rel inten) 150 (43), 137 (7.7),
188 (97); exact mass (CI) calcd for C10
232.0688, C10H19 BrN 234.0680, found 234.0689.
H
19 BrN 232.0700, found
8
1
+
)
1
3
1
1
Ack n ow led gm en t. We thank D. S. Watt and R. C.
Larock for helpful discussions.
36 (13), 123 (7.1), 122 (50), 110 (15), 108 (17), 69 (100); exact
mass calcd for C11
P r ep a r a tion of 1-br om od eca n en itr ile 12 (m eth od B):
TLC R (5% MTBE/petroleum ether) ) 0.26; IR (film) 2929, 2855,
245, 1463, 1427 cm-1; 1H NMR δ 3.41 (t, 2H, J ) 6.8 Hz), 2.34
H19N 165.1517, found 165.1502.
1
H and 13C spectra
Su p p or tin g In for m a tion Ava ila ble:
f
2
(
2
2
for compounds 2, 4, 6, 8, 10, and 12 (12 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
t, 2H, J ) 7.0 Hz), 1.86 (pentet, 2H, J ) 7.0 Hz), 1.66 (pentet,
H, J ) 7.2 Hz), 1.40 (m, 10H); 13C NMR δ u 119.7, 33.9, 32.6,
9.0, 28.53, 28.48 (2), 28.0, 25.2, 17.0; MS m/z (rel inten) 232
(
6) Trost, B. M.; Taber, D. F.; Alper, J . B. Tetrahedron Lett. 1976,
3
857.
J O971198H