Electrophilic cyanations using 1-cyanobenzotriazole: sp2 and sp carbanions

Full text of DOI:10.1021/jo981924w

J . Org. Chem. 1999, 64, 313-315
313
Electr op h ilic Cya n a tion s Usin g
-Cya n oben zotr ia zole: sp a n d sp
Sch em e 1
2
1
Ca r ba n ion s
Terry V. Hughes and Michael P. Cava*
Department of Chemistry, The University of Alabama,
Box 870336, Tuscaloosa, Alabama 35487-0336
Received September 22, 1998
In tr od u ction
7
methodology for the cyanations of acetylenes. A poor
yield, however, was obtained for the cyanation of a novel
thiophene (Table 1, entry 8). The simple arenyl anions
generated from 2-bromonaphthalene and 9-bromoan-
thracene gave good yields, 61-75%, of the cyanation
products (Table 1, entries 9 and 10).
The introduction of a cyano group via carbon-carbon
bond forming reactions is a fundamental process in
organic synthesis. While this transformation is usually
accomplished through the nucleophilic attack of a cyanide
-
ion (CN ) at an electrophilic carbon, a few reagents react
+
as a cyano cation (CN ) equivalent upon treatment with
1
-3
Exp er im en ta l Section
a carbanion. These include tosyl cyanide, 2-chloroben-
zylthiocyanate,4 and cyanogen chloride.5 Recently, we
described a new and convenient synthesis of 1-cyanoben-
1
Gen er a l Meth od s. Melting points are uncorrected. H NMR
spectra were obtained at 360 MHz, and chemical shifts are
(7.26 ppm). C NMR
spectra were obtained at 90 MHz and chemical shifts are
reported in ppm relative to internal CHCl (77 ppm). All
moisture- or air-sensitive reactions were carried out under an
atmosphere of nitrogen in oven-dried glassware. All reagents
were used as obtained from commercial suppliers except for the
following: THF was freshly distilled from sodium-benzophenone
6
13
zotriazole (1) and preliminary results showing its utility
reported in ppm relative to internal CHCl
3
as an electrophilic C-cyanating reagent by the conversion
of arylacetonitrile anions to the corresponding aryl ma-
lononitriles (Scheme 1). To expand the utility of 1 as a
reagent for electrophilic cyanations, we reacted 1 with a
variety of carbon nucleophiles. Thus the cyanations of
the anions of arenes, heteroarenes, and alkynes are
described.
3
6
8
ketyl. 1-Cyanobenzotriazole, 5,5′-dibromo-2,2′-bithiophene, 1-(p-
9
10
toluenesulfonyl)indole, 1-(p-toluenesulfonyl)pyrrole, N-dode-
1
1
cyl-2,5-bis(2-thienyl)pyrrole, and 1,3-di(2-thienyl)isothianaph-
thene12 were prepared according to published methods.
Gen er a l Cya n a tion P r oced u r e A (Nor m a l Ad d ition ).
Resu lts a n d Discu ssion
5
-Cya n o-2,2′-bith iop h en e (2a ) {Ta ble 1, en tr y 1a}. A solution
The order of addition was found to influence the yields
of the cyanation reactions with inverse additions giving
higher yields. For example, Table 1, entry 1a, shows a
of 2,2′-bithiophene (1.06 g, 6.38 mmol) in THF (45 mL) was
cooled to -78 °C, and 2.5 M BuLi (3.0 mL, 7.5 mmol) was added.
The solution was then stirred at 0 °C for 30 min and cooled to
-78 °C, and a solution of 1-cyanobenzotriazole (1.07 g, 7.4 mmol)
in THF (15 mL) was added via a syringe. The solution was
stirred at -78 °C for 1 h, warmed to room temperature, and
stirred for 1 h. The solution was then poured into 10% HCl (300
4
0% yield for the normal addition of the bithiophene
anion to the electrophile 1. However, the same heteroare-
nyl anion gave a 68% yield (Table 1, entry 1b) for the
inverse addition of the electrophile to the anion. One
explanation for this is that the heteroarenyl anion can
react with the electrophile 1 or the heteroarenenitrile
formed during the reaction to give a bisheteroarene
imine. Therefore, through inverse addition, the concen-
tration of 1 is high relative to the heteroarenenitrile
formed during the reaction and the desired cyanation is
observed in better yield.
mL) in ice and extracted with CH
Na SO , and filtered, and the solvent was removed under
reduced pressure. The residue was purified via column chroma-
tography (SiO ) (hexanes/CH Cl ) to give 2a (0.49 g, 40%) as a
pale yellow solid: mp 72-74 °C; H NMR (CDCl
2
Cl
2
(2 × 100 mL), dried over
2
4
2
2
2
1
3
) δ 7.52 (d, 1H,
J ) 3.91 Hz), 7.35 (d, 1H, J ) 5.07 Hz), 7.28 (d, 1H, J ) 3.80
Hz), 7.13 (d, 1H, J ) 3.91 Hz), 7.07 (dd, 1H, J ) 5.14, 1.17 Hz);
1
3
C NMR (CDCl
3
) δ 144.61, 138.19, 134.78, 128.27, 126.89,
) 3028, 2224, 1454,
: C, 56.51; H, 2.63; N, 7.32;
1
1
25.99, 123.40, 114.11, 107.42; IR (CHCl
3
Overall, the cyanation reactions worked in poor to good
yields depending on the nucleophile used. Good yields,
-1
9 5 2
223 cm . Anal. Calcd for C H NS
S, 33.53. Found: C, 56.57; H, 2.62; N, 7.23; S, 33.54.
6
1-83%, were obtained for the cyanations of the thiophene
Gen er a l Cya n a tion P r oced u r e B (In ver se Ad d ition ).
-Cya n o-2,2′-bith iop h en e (2a ) {Ta ble 1, en tr y 1b}. A solu-
tion of 2,2′-bithiophene (1.01 g, 6.07 mmol) in THF (45 mL) was
cooled to -78 °C, and 2.5 M BuLi (3.0 mL, 7.5 mmol) was added.
The solution was then stirred at 0 °C for 30 min and cooled to
5
ring system (Table 1, entries 1, 3, and 7) where the
heteroarene anion was generated either by direct lithia-
tion or lithium/halogen exchange and for the cyanation
of phenylacetylene (Table 1, entry 4). The latter example
may be especially useful as an addition to the current
-
78 °C. This solution was added via cannula to a cooled (-78
(
7) Modern Acetylene Chemistry; Stang, P. J ., Diederich, F., Eds.;
(
1) Kahne, D.; Collum, D. B. Tetrahedron Lett. 1981, 22, 5011-5014.
VCH: Weinheim, 1995; pp 33-37.
(2) Miyashita, A.; Nagasaki, I.; Kawano, A.; Suzuki, Y.; Iwamoto,
(8) Pham, C. V.; Burkhardt, A.; Shabana. R.; Cunningham, D. D.;
Mark, H. B.; Zimmer, H. Phosphorus, Sulfur, Silicon 1989, 46, 153-
168.
K.-I.; Higashino, T. Heterocycles 1997, 45, 745-755.
(3) Nagasaki, I.; Suzuki, Y.; Iwamoto, K.-I.; Higashino, T.; Miyashita,
A. Heterocycles 1997, 46, 443-450.
(9) Illi, V. O. Synthesis 1979, 136.
(
4) Davis, W. A.; Cava, M. P. J . Org. Chem. 1983, 48, 2774-2775.
5) Wheland, R. C.; Martin, E. L. J . Org. Chem. 1975, 40, 3101-
(10) Papadopoulos, E. P.; Haidar, N. F. Tetrahedron Lett. 1968,
1721-1723.
(11) Niziurski-Mann, R. E.; Cava, M. P. Adv. Mater. 1993, 5, 547-
551.
(
3
109.
(6) Hughes, T. V.; Hammond, S. D.; Cava, M. P. J . Org. Chem. 1998,
6
3, 401-402.
(12) Lorcy, D.; Cava, M. P. Adv. Mater. 1992, 4, 562-564.
1
0.1021/jo981924w CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/16/1998

3
14 J . Org. Chem., Vol. 64, No. 1, 1999
Ta ble 1. Rea ction of th e Su bstr a te An ion w ith 1-Cya n oben zotr ia zole (1)
Notes
a
Yields for isolated compounds. Normal addition. c Inverse addition. d TMEDA used; no. of equivalents used ) no. of equivalents of
b
e
f
BuLi used. Reaction temperature was maintained at -78 °C until the reaction was quenched with 1. Et2O used as solvent.
1
+
°
(
C) solution of 1-cyanobenzotriazole (1.09 g, 7.57 mmol) in THF
15 mL). The solution was stirred at - 78 °C for 1 h, warmed to
room temperature, and stirred for 1 h. The solution was poured
into 10% HCl (300 mL) in ice and extracted with CH Cl
(2 ×
0 mL), dried over Na SO , and filtered, and the solvent was
removed under reduced pressure. The residue was purified via
cm- ; MS m/z (M ) 296. Anal. Calcd for C16
H N O S: C, 64.85;
12 2 2
H, 4.08; N, 9.45; S, 10.82. Found: C, 64.56; H, 4.13; N, 9.48; S,
10.70.
2
2
1
-(p-Tolu en esu lfon yl)-2-cya n op yr r ole (5): white crystals,
8
2
4
1
mp 114-115 °C; H NMR (CDCl
3
) δ 7.93 (d, 2H, J ) 8.38 Hz),
.47 (dd, 1H, 3.24, 1.63 Hz), 7.37 (d, 2H, J ) 8.31 Hz), 6.95 (dd,
H, J ) 3.70, 1.57 Hz), 6.32 (t, 1H, J ) 3.41 Hz), 2.44 (s, 3H);
7
1
column chromatography (SiO
g, 68%).
2 2 2
) (hexanes/CH Cl ) to give 2a (0.79
13
C NMR (CDCl
3
) δ 146.52, 134.12, 130.36, 127.85, 126.57,
5
,5′-Dicya n o-2,2′-bith iop h en e (2b): pale yellow solid, mp
126.57, 126.51, 112.30, 111.63, 103.74, 21.69; IR (KBr) 3148,
975, 2226, 1594 cm . Anal. Calcd for C12H N O S: C, 58.52;
10 2 2
H, 4.09; N, 11.37; S, 13.02. Found: C, 58.49; H, 4.11; N, 11.36;
S, 13.02.
1
2
(
1
60-262 °C; H NMR (CDCl
3
) δ 7.58 (d, 2H, J ) 3.92 Hz), 7.26
d, 2H, J ) 3.00 Hz); C NMR (CDCl ) δ 141.38, 138.29, 125.67,
13.32, 110.30; IR (CHCl ) 3027, 1224 cm . Anal. Calcd for
: C, 55.53; H, 1.86; N, 12.95; S, 29.65. Found: C,
5.52; H, 1.85; N, 12.71; S, 29.85.
-P h en yl-2-p r op yn en itr ile (3): white crystalline solid with
-1
2
1
3
3
-
1
3
10 4 2 2
C H N S
5
1
-Dod ecyl-2-(5-cya n oth ien yl)-5-th ien ylp yr r ole (6a ): thick
1
green oil; H NMR (CDCl
H, J ) 4.67, 1.20 Hz), 7.11-7.08 (m, 2H), 7.03(d, 1H, J ) 3.91
Hz), 6.45 (d, 1H, J ) 3.70 Hz), 6.33 (d, 1H, J ) 3.65 Hz), 4.14 (t,
H, J ) 7.81 Hz), 1.24-1.14 (m, 20H), 0.88 (t, 3H, J ) 6.65 Hz);
C NMR (CDCl ) δ 142.78, 137.75, 133.96, 130.51, 127.37,
3
26.60, 126.13, 125.93, 124.44, 114.29, 112.63, 111.53, 107.64,
3
) δ 7.57 (d, 1H, J ) 3.92 Hz), 7.35 (dd,
3
1
1
3
1
a strong mint odor, mp 35-37 °C (mp lit 37-39 °C); H NMR
(CDCl
3
) δ 7.61 (d, 2H, J ) 7.46 Hz), 7.54 (t, 1H, J ) 7.34 Hz),
.42 (t, 2H, J ) 7.49 Hz); 13C NMR (CDCl
) δ 133.39, 131.82,
28.79, 117.38, 105.36, 82.92, 62.97; IR (KBr) 2975, 2271, 2145
2
7
1
cm
3
13
1
4
-
1
.
5.44, 31.87, 31.12, 29.57, 29.43, 29.30, 28.87, 26.29, 22.67, 14.09;
IR (NaCl) neat 3103, 2926, 2853, 2215, 1544 cm ; HRMS calcd
1
-(p-Tolu en esu lfon yl)-2-cya n oin d ole (4): white solid, mp
-1
1
1
60-162 °C; H NMR (CDCl
3
) δ 8.22 (d, 1H, J ) 8.17 Hz), 7.90
for C25
-Dod ecyl-2,5-d i(5-cya n ot h ien yl)p yr r ole (6b): thick oil
which solidified on standing to give a yellow solid, mp 60-61
32 2 2
H N S 424.2007, found 424.2022.
(
7
d, 2H, J ) 8.39 Hz), 7.58 (d, 1H, J ) 8.08 Hz), 7.54 (t, 1H, J )
1
.34 Hz), 7.36 (s, 1H), 7.34 (d, 1H, J ) 5.61 Hz), 7.27 (d, 2H, J
1
3
)
1
1
3
8.57 Hz), 2.37 (s, 3H); C NMR (CDCl ) δ 146.10, 136.63,
1
°
)
(
C; H NMR (CDCl
3.89 Hz), 6.46 (s, 2H), 4.16 (t, 2H, J ) 7.61 Hz), 1.24-1.15
m, 20H), 0.88 (t, 3H, J ) 7.46 Hz); 13C NMR (CDCl
) δ 141.60,
37.75, 127.99, 125.45, 113.92, 113.21, 108.76, 45.73, 31.84,
31.14, 29.54, 29.40, 29.27, 28.85, 26.24, 22.63, 14.07; IR (KBr)
3
) δ 7.60 (d, 2H, J ) 3.88 Hz), 7.06 (d, 2H, J
34.38, 130.19, 128.58, 127.58, 127.48, 127.11, 124.68, 122.98,
22.48, 114.59, 112.16, 108.99, 21.60; IR (KBr) 3140, 2975, 2224
3
1
(13) Luo, F.; Wang, M.; Wang, R. Org. Synth. 1998, 75, 146-151.

Notes
121, 2920, 2850, 2214, 1556 cm-1. Anal. Calcd for C26
J . Org. Chem., Vol. 64, No. 1, 1999 315
3
H
31
N
3
S
2
:
2-Cya n on a p h th a len e (8): white solid, mp 64-66 °C (mp
lit.14 66 °C); H NMR (CDCl
7.65-7.57 (m, 3H); C NMR (CDCl ) δ 134.56, 134.04, 132.15,
129.10, 128.96, 128.31, 127.96, 127.57, 126.23, 119.17, 109.30;
1
) δ 8.22 (s, 1H), 7.91-7.87 (m, 3H),
C, 69.45; H, 6.95; N, 9.34; S, 14.26. Found: C, 69.46; H, 7.06; N,
.41; S, 14.13.
-(5-cya n oth ien yl)-2-th ien ylben zo[c]th iop h en e (7a ): red
3
1
3
9
3
1
1
-1
solid: mp 153-155 °C; H NMR (CDCl
Hz), 7.91 (d, 1H, J ) 8.83 Hz), 7.63 (d, 1H, J ) 3.95 Hz), 745
dd, 1H, J ) 5.02, 0.88 Hz), 7.40 (dd, 1H, J ) 3.74, 0.96 Hz),
.31 (d, 1H, J ) 3.99 Hz), 7.24-7.17 (m, 3H); 13C NMR (CDCl
)
3
3
) δ 7.99 (d, 1H, J ) 8.78
IR (KBr) 3057, 2930, 2226 cm
.
9
-Cya n oa n th r a cen e (9): yellow solid, mp 167.5-169 °C (mp
1
(
7
lit.15 170-172 °C); H NMR (CDCl
J ) 8.59 Hz), 8.09 (d, 2H, J ) 8.49 Hz), 7.73 (t, 2H, J ) 7.99
Hz), 7.60 (t, 2H, J ) 6.75 Hz); 13C NMR (CDCl
) δ 133.21, 132.66,
130.53, 128.88, 128.26, 126.28, 125.19, 117.20, 105.32; IR (KBr)
) δ 8.69 (s, 1H), 8.43 (d, 2H,
3
δ 143.14, 137.97, 136.26, 135.38, 134.67, 129.92, 128.09, 126.57,
3
1
1
26.46, 126.44, 125.13, 124.40, 123.11, 121.96, 120.76, 114.28,
07.73; IR (KBr) 2973, 2209, 1435, 1053 cm-1; HRMS calcd for
-
1
3
059, 2210, 735 cm
.
C
17
H
9
NS
O: C, 61.41; H, 3.03; N, 4.21; S, 28.93. Found: C, 61.11;
H, 3.14; N, 4.13; S, 28.69.
,3-Di(2-t h ien yl)b en zo[c]t h iop h en e-5,5′-d ica r b on it r ile
3 9 3
322.9897, found 322.9923. Anal. Calcd for C17H NS ‚
1
/2 H
2
1
Ack n ow led gm en t. The authors thank the National
Science Foundation for a grant (CHE-9612350) in
partial support of this work.
1
(
7b): red crystals, mp 226-228 °C; H NMR (CDCl
H, J ) 2.96 Hz), 7.93 (d, 1H, J ) 3.14 Hz), 7.66 (d, 2H, J )
.96 Hz), 7.35 (d, 2H, J ) 3.95 Hz), 7.32 (d, 1H, J ) 2.92 Hz),
.30 (d, 1H, J ) 2.97 Hz); 13C NMR (CDCl
) δ 142.01, 138.08,
36.41, 126.75, 126.18, 125.57, 121.20, 113.91, 109.19; IR (KBr)
958, 2925, 2199, 1432 cm-1. Anal. Calcd for C18
: C,
3
) δ 7.95 (d,
1
3
7
1
2
6
7
3
J O981924W
8 2 3
H N S
2.04; H, 2.31; N, 8.04; S, 27.60. Found: C, 61.88; H, 2.41; N,
.92; S, 27.65.
(14) Gasiorowski, K.; Merz, V. Ber. 1885, 18, 1001-1014.
(15) Karrer, P.; Zeller, E. Helv. Chim. Acta 1919, 2, 482-486.