Expedient acylations of primary and secondary alkyl cyanides to α-substituted β-ketonitriles

Article abstract of DOI:10.1021/jo026796x

Primary and secondary cyanides are efficiently acylated with N-acylbenzotriazoles 3a-f (derived from a variety of acids) to afford the corresponding α-substituted β-ketonitriles 5a-r in 67-96% yields.

Full text of DOI:10.1021/jo026796x

Exp ed ien t Acyla tion s of P r im a r y a n d Secon d a r y Alk yl Cya n id es to
r-Su bstitu ted â-Keton itr iles
Alan R. Katritzky,* Ashraf A. A. Abdel-Fattah, and Mingyi Wang
Department of Chemistry, Center for Heterocyclic Compounds, University of Florida,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received December 3, 2002
Primary and secondary cyanides are efficiently acylated with N-acylbenzotriazoles 3a -f (derived
from a variety of acids) to afford the corresponding R-substituted â-ketonitriles 5a -r in 67-96%
yields.
In tr od u ction
of â-ketonitriles unsubstituted at the R-position.12 Ad-
ditionally, the range of â-ketonitrile structures reported
is quite limited: for example, ref 11b is confined to
structures of types ArCOCH(Ph)CN and ArCOCH2CN.
All 18 â-ketonitriles reported in the present manuscript
are novel.
Acylazoles are known as efficient acylating reagents.13
We have recently used 1-(trifluoroacetyl)benzotriazole for
trifluoroacetylation,14 and 1-formylbenzotriazole for the
formylation of amines and alcohols.15 1-Acylbenzotri-
azoles are good C-acylating reagents for ketones16 and
O-acylating reagents for aldehydes.17 We now report an
efficient and convenient procedure for the preparation
of a variety of â-ketonitriles 5a -r by the acylation of
nitriles 4a -j with N-acylbenzotriazoles 3a -f in good to
excellent yields.
â-Ketonitriles are an important class of difunctional
intermediates for the synthesis of many heterocycles,
including dihydropyrans and dihydrothiopyrans,1 pyra-
zoles,2 pyrimidines,3 pyridones,4 and quinolines.5 Recent
interest in â-ketonitriles has been focused on their
bioreduction6 and parallel kinetic resolution7 for the
preparation of enantiopure ketones and alcohols contain-
ing a quaternary stereocenter in line with the growing
importance of optically active â-hydroxy nitriles as
intermediates in the preparation of γ-amino alcohols (like
the antidepressant fluoxetine).8 In this respect, the
diversity of the â-ketonitriles available significantly
impacts the range of structures which can be accessed.
Classical and conventional methods for the syntheses
of â-ketonitriles have been well documented.9 Due to the
acidity of protons adjacent to a nitrile group, a simple
and direct preparation of â-ketonitriles is the acylation
of acetonitriles. Early methods employing this route
require harsh reaction conditions, e.g., sodium amide in
liquid ammonia.10 Recently the use of LDA or UDP
systems (ultrasonic irradiation of a suspension of potas-
sium in toluene) has been successful.11 However, all these
previous methods are apparently limited to the synthesis
Resu lts a n d Discu ssion
N-Acylbenzotriazoles 3a -f were prepared in excellent
yields according to the literature procedure.18 Treatment
of acetonitriles 4a -j with n-butyllithium in THF at -78
°C or t-BuOK in DMSO at 20 °C, followed by the addition
of a solution of N-acylbenzotriazoles 3a -f in the corre-
sponding same solvent, provided the corresponding â-
ketonitriles 5a -r . The TLC and NMR of the crude
products show that the reactions are very clean (usually
benzotriazole is the only byproduct, but occasionally,
small amounts of the unreacted starting N-acylbenzo-
triazoles 3 were detected). The pure aliphatic, aromatic,
and heteroaromatic â-ketonitriles 5a -r were isolated in
67-96% yields (Scheme 1 and Table 1).
(1) Augustin, M.; J ahreis, G.; Rudorf, W.-D. Synthesis 1977, 472.
(2) Watson, S. P.; Wilson, R. D.; J udd, D. B.; Richards, S. A.
Tetrahedron Lett. 1997, 38, 9065.
(3) (a) Kambe, S.; Saito, K.; Kishi, H. Synthesis 1979, 287. (b) Baker,
B. R.; J ordaan, J . H. J . Heterocycl. Chem. 1966, 3, 324. (c) Wajon, J .
F. M.; Arens, J . F. Recl. Trav. Chim. Pays-BQS 1957, 79.
(4) Hauser, C. R.; Eby, C. J . J . Am. Chem. Soc. 1957, 79, 728.
(5) Hauser, C. R.; Murray, J . G. J . Am. Chem. Soc. 1955, 77, 2851.
(6) (a) Dehli, J . R.; Gotor, V. Tetrahedron: Asymmetry 2000, 11, 3693.
(b) Dehli, J . R.; Gotor, V. Tetrahedron: Asymmetry 2001, 12, 1485. (c)
Mehmandoust, M.; Buisson, D.; Azerad, R. Tetrahedron Lett. 1995, 36,
6461. (d) Itoh, T.; Fukuda, T.; Fujisawa, T. Bull. Chem. Soc. J pn. 1989,
62, 3851.
(7) Dehli, J . R.; Gotor, V. J . Org. Chem. 2002, 67, 1716.
(8) Koenig, T. M.; Mitchell, D. Tetrahedron Lett. 1994, 35, 1339.
(9) North, M. In Comprehensive Organic Functional Group Trans-
formations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon Press: Oxford, UK, 1995; Vol. 3, Chapter 3.18, p 611.
(10) Eby, C. J .; Hauser, C. J . Am. Chem. Soc. 1957, 79, 723.
(11) (a) Kayaleh, N. E.; Gupta, R. C.; J ohnson, F. J . Org. Chem.
2000, 65, 4515. (b) Gao, Y.; Wang, H.; Xu, M.; Lian, H.; Pan, Y.; Shi,
Y. Org. Prep. Proced. Int. 2001, 33, 351.
(12) Rao, D.; Stuber, F. A. Synthesis 1983, 308.
(13) Staab, H. A.; Bauer, H.; Schneider, K. M. Azolides in Organic
Synthesis and Biochemistry; Wiley-VCH: Weinheim, Germany, 1998;
pp 129-205.
(14) Katritzky, A. R.; Yang, B.; Semenzin, D. J . Org. Chem. 1997,
62, 726.
(15) Katritzky, A. R.; Chang, H.-X.; Yang, B. Synthesis 1995, 503.
(16) Katritzky, A. R.; Pastor, A. J . Org. Chem. 2000, 65, 3679.
(17) Katritzky, A. R.; Pastor, A.; Voronkov, M. V. J . Heterocycl.
Chem. 1999, 36, 777.
(18) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J . Org. Chem. 2000, 65,
8210.
10.1021/jo026796x CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/09/2003
4932
J . Org. Chem. 2003, 68, 4932-4934

Acylations of Alkyl Cyanides to â-Ketonitriles
SCHEME 1
cantly, our method provided a means to prepare â-keto-
nitriles 5f,i,n derived from secondary nitriles, which are
inaccessible by Claisen-type condensations.10
The present method is operationally simple and utilizes
easily prepared, stable N-acylbenzotriazoles as acylating
reagents, and the byproduct (benzotriazole) can be easily
removed by simply washing with saturated aqueous Na2-
CO3. The current results represent the first example of
the successful use of amides for the acylation of a nitrile.
In conclusion, we have developed a general, simple, and
efficient method for the synthesis of aliphatic, aromatic,
and heteroaromatic ketones bearing a cyano group at the
R-position utilizing readily accessible N-acylbenzotri-
azoles. The high yields of ketones 5a -r have proved
N-acylbenzotriazoles 3 to be convenient and valuable
alternative reagents for the C-acylation of nitriles.
Exp er im en ta l Section
Gen er a l. Melting points were determined on a hot-stage
apparatus and are uncorrected. NMR spectra were recorded
in CDCl3 with tetramethylsilane as internal standard for 1H
(300 MHz) or solvent as the internal standard for 13C (75 MHz).
Anhydrous THF was obtained by distillation immediately prior
to use. Column chromatography was conducted with silica gel
200-425 mesh. BtSO2CH3 (1) and N-acylbenzotriazoles 3a -f
were prepared according to literature procedures.18
Gen er a l P r oced u r es for th e P r ep a r a tion of â-Keton i-
tr iles 5a -r . Meth od A: n-Butyllithium (1.6 mL of 1.55 M in
hexane, 2.4 mmol) was added slowly with efficient stirring
under nitrogen to a solution of acetonitrile 4 (2 mmol) in
anhydrous THF (10 mL) at -78 °C. After 1 h, N-acylbenzo-
triazole 3 (2 mmol) was slowly added by syringe to minimize
the temperature increase that results from the exothermic
reaction. After the mixture was stirred for 2 h at -78 °C, the
resultant solution was allowed to attain room temperature.
Subsequently, the reaction mixture was poured into water (50
mL), acidified with 1 N HCl solution, and extracted with
EtOAc. The organic layer was washed with NaCl solution and
dried over MgSO4. Then solvent was evaporated in vacuo, and
the residue was subjected to column chromatography on silica
gel and eluted with a mixture of EtOAc/hexanes (1:5, v/v) to
give the desired product 5.
TABLE 1. P r ep a r a tion of â-Keton itr iles 5a -r via
C-Acyla tion of Aceton itr iles w ith N-Acylben zotr ia zoles
3a -f
from nitriles 4
yield
method (%)
entry
R of RCO
R1
R2
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
(CH3)2CHCH2
(CH3)2CHCH2
C6H5
C6H5
C6H5
H
4-BrC6H4
B
A
A
B
A
A
A
A
A
A
B
B
A
A
A
B
B
A
95
83
93
95
74
79
88
83
67
71
91
89
85
82
92
94
92
95
H
H
H
H
benzotriazol-1-yl
4-MeOC6H4
4-MeC6H4
CH3(CH2)2CH2
C6H5
CH3 C6H5
H
H
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
2-thienyl
2-thienyl
2-thienyl
2-thienyl
2-thienyl
2-furyl
H
C6H5CH2
CH3 C6H5
H
H
H
H
CH3(CH2)2CH2
4-BrC6H4
2,4-Cl2C6H3
C6H4CH2
CH3 C6H5
H
H
H
H
H
2,4-Cl2C6H3
naphth-1-yl
H
2-furyl
2-furyl
Meth od B: A mixture of an acetonitrile 4 (2 mmol) and
potassium tert-butoxide (2.2 mmol) in dimethyl sulfoxide (10
mL) was stirred while the temperature was maintained below
10 °C for 10 min. To the resulting solution was added
N-acylbenzotriazole 3 (2 mmol) in dimethylsulfoxide (10 mL)
dropwise, and the mixture was stirred at 25 °C for 12 h. The
mixture was poured into water (40 mL), acidified with 1 N
HCl, and then extracted with ethyl acetate (3 × 30 mL). The
extracts were washed with water and dried over MgSO4. After
the solvent was removed under reduced pressure, the residue
was placed in a silica gel column and eluted with a mixture of
EtOAc/hexanes (1:5, v/v) to give the desired product 5.
The structures of compounds 5a -r , which are all novel,
were supported by NMR spectroscopy and elemental
1
analyses. For example, in the H NMR spectrum of 5m ,
a methine proton appears at 4.34 ppm as a doublet of
doublets with coupling constants of 8.1and 6.5 Hz, and
the diastereotopic protons of the methylene group dis-
2
played an AB type spectrum at δ 3.38 (dd, J AB ) 13.9
3
Hz, J ) 6.2 Hz, 1H, A part of AB system) and 3.28 (dd,
3
2J AB ) 13.7 Hz, J ) 8.7 Hz, 1H, B part of AB system).
The signals that appear at δ 7.17 (t, J ) 4.1 Hz, 1H),
7.28-7.34 (m, 5H), 7.78 (d, J ) 4.8 Hz, 1H), and 7.81 (d,
J ) 3.7 Hz, 1H) were assigned to the protons from the
phenyl and thienyl moieties. The carbonyl and methine
groups appeared at δ 182.6 (CO) and 42.77 (CH), respec-
tively, in the 13C NMR spectrum.
2-(4-Br om op h en yl)-5-m eth yl-3-oxoh exa n en itr ile (5a ).
1
Colorless microcrystals (95%), mp 76-78 °C. H NMR δ 7.57
(d, J ) 8.4 Hz, 2H), 7.27 (d, J ) 4.8 Hz, 2H), 4.61 (s, 1H),
2.56-2.39 (m, 2H), 2.14 (septet, J ) 7.0 Hz, 1H), 0.86 (d, J )
4.5 Hz, 3H), 0.84 (d, J ) 4.4 Hz, 3H). 13C NMR δ 197.6, 132.7,
129.6, 128.6, 123.6, 115.9, 50.5, 48.50, 24.2, 22.1. Anal. Calcd
for C13H14BrNO: C, 55.73; H, 5.04; N, 5.00. Found: C, 55.54;
H, 5.07; N, 4.89.
This new synthetic procedure for the preparation of
â-ketonitriles offers advantages over the literature pro-
cedures. It has demonstrated good generality: it can be
used with aliphatic (to give 5a ,b), benzenoid (to give 5c-
j), and heterocyclic acylation reagents (thienyl to give
5k -o, furyl to give 5p -r ). Primary alkyl-, aryl-, and
heteroaryl-substituted nitriles can also be used. Signifi-
2-(1H-1,2,3-Ben zotr ia zol-1-yl)-5-m eth yl-3-oxoh exa n en i-
tr ile (5b). Brown microcrystals (83%), mp 108-110 °C. 1H
NMR δ 7.86 (d, J ) 8.0 Hz, 1H), 7.71 (d, J ) 7.8 Hz, 1H), 7.55
(dd, J ) 8.1, 6.9 Hz, 1H), 7.35-7.27 (m, 3H), 2.65 (d, J ) 6.9
Hz, 2H), 2.35-2.28 (m, 1H), 1.14 (d, J ) 6.0 Hz, 6H). 13C NMR
δ 170.9, 144.3, 131.7, 129.1, 125.6, 119.4, 114.7, 110.7, 88.2,
J . Org. Chem, Vol. 68, No. 12, 2003 4933

Katritzky et al.
42.0, 27.2, 22.2. Anal. Calcd for C13H14N4O: C, 64.45; H, 5.82.
Found: C, 64.58; H, 6.04.
115.1, 43.2. Anal. Calcd for C13H7Cl2NOS: C, 52.72; H, 2.38;
N, 4.73. Found: C, 53.08; H, 2.44; N, 4.51.
2-(4-Meth oxyph en yl)-3-oxo-3-ph en ylpr opan en itr ile (5c).
Yellow microcrystals (93%), mp 76-78 °C. H NMR δ 7.93 (d,
J ) 7.4 Hz, 2H), 7.58 (t, J ) 7.4 Hz, 1H), 7.45 (t, J ) 7.7 Hz,
2H), 7.34 (d, J ) 8.7 Hz, 2H), 6.90 (d, J ) 8.8 Hz, 2H), 5.57 (s,
1H), 3.78 (s, 3H). 13C NMR δ 189.1, 160.1, 134.3, 133.6, 129.5,
129.2, 129.0, 122.1, 116.8, 115.0, 55.3, 45.9. Anal. Calcd for
2-Ben zyl-3-oxo-3-(2-th ien yl)p r op a n en itr ile (5m ). Color-
less plates (85%), mp 72-74 °C. 1H NMR δ 7.81 (d, J ) 3.7
Hz, 1H), 7.78 (d, J ) 4.8 Hz, 1H), 7.28-7.34 (m, 5H), 7.17 (dd,
J ) 4.1, 4.4 Hz, 1H), 4.34 (dd, J ) 6.5, 8.1 Hz, 1H), [3.38 (dd,
1
3
2J AB ) 13.9 Hz, J ) 6.2 Hz, 1H, A part of AB system), 3.28
2
3
(dd, J AB ) 13.7 Hz, J ) 8.7 Hz, 1H, B part of AB system)].
13C NMR δ 182.6, 140.8, 136.3, 135.7, 133.8, 129.0, 128.9,
128.7, 127.7, 116.8, 42.8, 35.9. Anal. Calcd for C14H11NOS: C,
69.68; H, 4.59; N, 5.80. Found: C, 69.37; H, 4.58; N, 5.75.
2-Meth yl-3-oxo-2-ph en yl-3-(th ien yl)pr opan en itr ile (5n ).
C
16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C, 76.15; H,
5.35; N, 5.47.
2-(4-Meth ylp h en yl)-3-oxo-3-p h en ylp r op a n en itr ile (5d ).
1
Colorless plates (95%), mp 69-71 °C. H NMR δ 7.94 (d, J )
1
7.6 Hz, 2H), 7.59-7.43 (m, 3H), 7.32 (d, J ) 7.8 Hz, 2H), 7.19
(d, J ) 7.7 Hz, 2H), 5.57 (s, 1H), 2.33 (s, 3H). 13C NMR δ 189.0,
139.2, 134.3, 133.6, 130.3, 129.2, 129.0, 128.1, 127.3, 116.7,
46.4, 21.1. Anal. Calcd for C16H13NO: C, 81.68; H, 5.57; N,
5.95. Found: C, 81.61; H, 5.35; N, 5.94.
Colorless prisms (82%), mp 66-68 °C. H NMR δ 7.64 (d, J )
4.0 Hz, 1H), 7.60 (d, J ) 4.9 Hz, 1H), 7.51-7.35 (m, 5H), 6.98
(dd, J ) 4.7, 4.3 Hz, 1H), 2.04 (s, 3H). 13C NMR δ 183.9, 139.6,
137.3, 135.2, 135.1, 129.6, 128.7, 128.3, 125.6, 120.4, 51.7, 26.5.
Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80.
Found: C, 69.51; H, 4.80; N, 5.77.
2-Ben zoylh exa n en it r ile (5e). Pale yellow oil (74%). 1H
NMR δ 7.96 (d, J ) 7.4 Hz, 2H), 7.68-7.63 (m, 1H), 7.55-
7.50 (m, 2H), 4.37 (t, J ) 7.1 Hz, 1H), 2.04-1.96 (m, 2H), 1.58-
1.35 (m, 4H), 0.93 (t, J ) 7.2 Hz, 3H). 13C NMR δ 190.9, 134.4,
133.9, 129.0, 128.7, 117.4, 40.0, 29.6, 29.1, 22.0, 13.6. Anal.
Calcd for C13H15NO: N, 6.96. Found: N, 6.67.
3-Oxo-3-(2-th ien yl)p r op a n en itr ile (5o). Colorless plates
(92%), mp 124-126 °C. 1H NMR δ 7.81-7.78 (m, 2H), 7.20
(dd, J ) 1.0, 4.0 Hz, 1H), 4.02 (s, 2H). 13C NMR δ 179.5, 140.8,
136.2, 133.7, 128.7, 113.4, 29.5. Anal. Calcd for C7H5NOS: C,
55.61; H, 3.33; N, 9.26. Found: C, 55.48; H, 3.28; N, 9.12.
2-(2,4-Dich lor op h e n yl)-3-(2-fu r yl)-3-oxop r op a n e n i-
2-Meth yl-3-oxo-2,3-d ip h en ylp r op a n en itr ile (5f). Color-
1
less oil (79%). H NMR δ 7.87 (d, J ) 7.4 Hz, 2H), 7.49-7.29
1
tr ile (5p ). Colorless prisms (94%), mp 86-88 °C. H NMR δ
(m, 8H), 1.91 (s, 3H). 13C NMR δ 191.0, 137.3, 133.6, 133.3,
130.0, 129.7, 128.5, 128.4, 125.3, 120.4, 51.5, 27.3. Anal. Calcd
for C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C, 81.36; H,
5.95; N, 5.92.
7.70 (br s, 1H), 7.57 (d, J ) 8.4 Hz, 1H), 7.47 (d, J ) 2.1 Hz,
1H), 7.45 (d, J ) 3.7 Hz, 1H), 7.36 (dd, J ) 2.1, 8.4 Hz, 1H),
6.64 (dd, J ) 1.5, 3.7 Hz, 1H), 5.93 (s, 1H). 13C NMR δ 175.7,
149.7, 148.3, 136.1, 134.0, 131.2, 129.8, 128.2, 126.8, 120.6,
114.9, 113.4, 42.3. Anal. Calcd for C13H7Cl2NO2: C, 55.74; H,
2.52; N, 5.00. Found: C, 55.72; H, 2.47; N, 4.94.
3-(4-Meth ylp h en yl)-3-oxop r op a n en itr ile (5g). Colorless
1
plates (88%), mp 94-96 °C (lit.11b mp 175-176 °C). H NMR
δ 7.82 (d, J ) 8.2 Hz, 2H), 7.32 (d, J ) 8.0 Hz, 2H), 4.06 (s,
2H), 2.44 (s, 3H). 13C NMR δ 186.6, 145.9, 131.8, 129.8, 128.5,
113.9, 29.2, 21.8. Anal. Calcd for C10H9NO: C, 75.45; H, 5.70;
N, 8.80. Found: C, 75.09; H, 5.86; N, 8.77.
3-(2-Fu r yl)-2-(1-n aph th yl)-3-oxopr opan en itr ile (5q). Col-
1
orless plates (92%), mp 96-98 °C. H NMR δ 8.08 (d, J ) 8.4
Hz, 1H), 7.89-7.86 (m, 2H), 7.75 (d, J ) 7.1 Hz, 1H), 7.62-
7.46 (m, 4H), 7.30 (d, J ) 3.7 Hz, 1H), 6.49 (dd, J ) 1.7, 3.7
Hz, 1H), 6.10 (s, 1H). 13C NMR δ 177.4, 149.9, 147.7, 134.0,
130.4, 130.1, 129.2, 128.0, 127.4, 126.4, 125.8, 125.4, 122.5,
120.3, 116.0, 113.2, 44.0. Anal. Calcd for C17H11NO2: C, 78.15;
H, 4.24; N, 5.36. Found: C, 78.49; H, 4.39; N, 5.22.
2-Ben zyl-3-(4-m eth ylp h en yl)-3-oxop r op a n en itr ile (5h ).
1
Colorless plates (83%), mp 65-67 °C. H NMR δ 7.85 (d, J )
8.1 Hz, 2H), 7.35-7.25 (m, 7H), 4.50 (dd, J ) 5.8, 5.9 Hz, 1H),
2
[3.34 (dd, J AB ) 13.9 Hz, 3J ) 5.6 Hz, 1H, A part of AB
2
3
system), 3.22 (dd, J AB ) 13.7 Hz, J ) 8.8 Hz, 1H, B part of
AB system)], 2.43 (s, 3H). 13C NMR δ 189.5, 145.8, 136.0, 131.5,
129.8, 129.0, 128.9, 128.8, 127.6, 117.1, 41.6, 35.5, 21.8. Anal.
Calcd for C17H15NO: C, 81.90; H, 6.06; N, 5.62. Found: C,
81.82; H, 6.35; N, 5.59.
3-(2-F u r yl)-3-oxop r op a n en itr ile (5r ). Colorless plates
1
(95%), mp 66-68 °C (lit.11b mp 76-78 °C). H NMR δ 7.68 (br
s, 1H), 7.39 (d, J ) 3.6 Hz, 1H), 6.65 (dd, J ) 1.5, 1.4 Hz, 1H),
3.99 (s, 2H). 13C NMR δ 175.7, 150.4, 147.8, 119.3, 113.3, 28.8.
Anal. Calcd for C7H5NO2: C, 62.22; H, 3.73; N, 10.37. Found:
C, 62.23; H, 3.73; N, 10.37.
2-Meth yl-3-(4-m eth ylp h en yl)-3-oxo-2-p h en ylp r op a n e-
n itr ile (5i). Colorless oil (67%). 1H NMR δ 7.78 (d, J ) 8.2
Hz, 2H), 7.48-7.33 (m, 5H), 7.13 (d, J ) 8.1 Hz, 2H), 2.32 (s,
3H), 1.91 (s, 3H). 13C NMR δ 190.6, 144.8, 137.7, 130.8, 130.4,
129.8, 129.2, 128.5, 125.5, 120.7, 51.5, 27.5, 217. Anal. Calcd
for C17H15NO: N, 5.62. Found: N, 5.54.
2-(4-Ch lor oben zoyl)h exa n en itr ile (5j). Pale yellow oil
(71%). 1H NMR δ 7.93 (br s, 1H), 7.84 (d, J ) 7.8 Hz, 1H),
7.63 (d, J ) 7.6 Hz, 1H), 7.58-7.48 (m, 1H), 4.31 (t, J ) 7.1
Hz, 1H), 2.01-1.98 (m, 2H), 1.58-1.38 (m, 4H), 0.94 (t, J )
7.1 Hz, 3H). 13C NMR δ 189.8, 135.5, 135.5, 134.4, 130.4, 128.7,
1-Isova ler oylben zotr ia zole (3a ). Pale yellow oil (95%). 1H
NMR δ 8.34 (d, J ) 8.4 Hz, 1H), 8.15 (d, J ) 8.4 Hz, 1H), 7.69
(t, J ) 7.6 Hz, 1H), 7.52 (t, J ) 7.7 Hz, 1H), 3.35 (d, J ) 7.0
Hz, 2H), 2.53-2.44 (septet, J ) 6.9 Hz, 1H), 1.25 (d, J ) 6.6
Hz, 6H). 13C NMR δ 172.0, 146.1, 131.0, 130.3, 126.0, 120.0,
114.4, 44.0, 25.6, 22.5. Anal. Calcd for C11H13N3O: N, 20.67.
Found: N, 20.53.
1-(2-Th ien ylca r bon yl)ben zotr ia zole (3f). Colorless mac-
1
rocrystals (93%), mp 166-168 °C. H NMR δ 8.58 (d, J ) 3.9
Hz, 1H), 8.40 (d, J ) 5.2 Hz, 1H), 8.16 (d, J ) 8.4 Hz, 1H),
7.89 (d, J ) 5.0 Hz, 1H), 7.69 (t, J ) 7.6 Hz, 1H), 7.55 (t, J )
7.7 Hz, 1H), 7.28 (t, J ) 3.5 Hz, 1H). 13C NMR δ 159.2, 145.8,
138.5, 137.2, 133.5, 132.1, 130.5, 128.1, 126.3, 120.2, 114.8.
Anal. Calcd for C11H7N3OS: C, 57.63; H, 3.08; N, 18.33.
Found: C, 57.64; H, 3.07; N, 18.24.
126.7, 117.0, 40.1, 29.4, 29.0, 22.0, 13.6. Anal. Calcd for C13H15
NO: N, 5.94. Found: N, 6.02.
-
2-(4-Br om op h en yl)-3-oxo-3-(2-t h ien yl)p r op a n en it r ile
1
(5k ). Colorless needles (91%), mp 74-76 °C. H NMR δ 7.88
(dd, J ) 1.0, 3.9 Hz, 1H), 7.82 (dd, J ) 1.1, 4.9, Hz, 1H), 7.59
(d, J ) 8.7 Hz, 2H), 7.40 (d, J ) 8,7 Hz, 2H), 7.21 (dd, J ) 1.0,
4.4 Hz, 1H), 5.45 (s, 1H). 13C NMR δ 180.9, 139.8, 136.7, 134.4,
132.7, 129.8, 129.3, 128.8, 123.6, 115.8, 46.8. Anal. Calcd for
Ack n ow led gm en t. Ashraf A. Abdel-Fattah grate-
fully acknowledges Prof. Dr. Samy A. Essway for his
encouragement.
C
13H8BrNOS: C, 51.00; H, 2.63; N, 4.57. Found: C, 51.04; H,
2.53; N, 4.44.
2-(2,4-Dich lor op h en yl)-3-oxo-3-(2-t h ien yl)p r op a n en i-
tr ile (5l). Colorless plates (89%), mp 89-91 °C. 1H NMR δ
7.90 (d, J ) 3.9 Hz, 1H), 7.80 (d, J ) 4.9 Hz, 1H), 7.58 (d, J )
8.4 Hz, 1H), 7.47 (br s, 1H), 7.36 (dd, J ) 1.8, 8.2 Hz, 1H),
7.19 (t, J ) 4.3 Hz, 1H), 5.92 (s, 1H). 13C NMR δ 180.0, 140.1,
136.9, 136.3, 134.2, 133.8, 131.1, 129.9, 128.8, 128.3, 127.3,
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 5a -r and 3a ,f. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O026796X
4934 J . Org. Chem., Vol. 68, No. 12, 2003