A novel route to imidoylbenzotriazoles and their application for the synthesis of enaminones

Article abstract of DOI:10.1021/jo0496594

Reactions of secondary amides 2a-i with 1-chloro-1H-benzotriazole and triphenylphosphine give imidoylbenzotriazoles 3a-i. The treatment of 3a,b,e,g with silyl enol ethers 5a,b in the presence of potassium tert-butoxide provides a new general approach to enaminoketones 6a-h.

Full text of DOI:10.1021/jo0496594

SCHEME 1
A Novel Rou te to Im id oylben zotr ia zoles
a n d Th eir Ap p lica tion for th e Syn th esis of
En a m in on es
Alan R. Katritzky,* Amy E. Hayden,
Kostyantyn Kirichenko, Phillip Pelphrey, and Yu J i
Center for Heterocyclic Compounds, University of Florida,
Department of Chemistry, Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received March 1, 2004
Abstr act: Reactions of secondary amides 2a-i with 1-chloro-
1H-benzotriazole and triphenylphosphine give imidoylben-
zotriazoles 3a -i. The treatment of 3a ,b,e,g with silyl enol
ethers 5a ,b in the presence of potassium tert-butoxide
provides a new general approach to enaminoketones 6a -h .
heterocyclic compounds, such as 1,5-benzodiazepine,12
1,4-dihydropyridine,13 furoisoquinoline,14 indole,15 isox-
azole,16 pyrrolo-1,2,4-triazine,17 pyrimidine,18 pyridino-
ne,19 and quinoline,19b,20 derivatives.
Imidoyl chlorides1 1 (Scheme 1) are important inter-
mediates and precursors for the synthesis of numerous
functionalities, including amidines,2 imidates,2a,3 ami-
doximes,4 amidrazones,4c,d imidonitriles,5 thioamides,6
diacylamines,3b imines,7 and heterocyclic compounds.4c,d,5a
Imidoylbenzotriazoles 3 have become important as
stable alternatives to the corresponding imidoyl chlorides
1.8 Major synthetic strategies utilized for the preparation
of imidoylbenzotriazoles 3 include the following (Scheme
1): (i) the reaction of secondary amides 2 with benzo-
triazole and POCl3 in the presence of triethylamine;8a (ii)
the reaction of secondary amides 2 and in situ prepared
1,1′-sulfinyldibenzotriazole;8b (iii) the one-pot reaction of
oximes with 1-(p-toluenesulfonyl)benzotriazole;9 (iv) the
condensation of isocyanates with 1-acyl-benzotriazoles;10
(v) the reaction of isonitriles with N-(aminoalkyl)benzo-
triazoles in the presence of boron trifluoride etherate.8d
The enaminone class of compounds11 represents ver-
satile and useful building blocks for the synthesis of
The available methods for the preparation of enami-
nones can be classified according to the bond formed
(Scheme 2). Five approaches form bond a : (i) reactions
of 1,3-diketones with amines in the presence of cata-
lysts;15,21 (ii) addition of amines to acylacetylenes;15,20a,22
(iii) palladium-assisted amination of R-keto olefines15,23
or amination with O-methylhydroxylamines in the pres-
ence of base;24 (iv) additions of amines to 3-oxo-2,3-
dihydrothiophene 1,1-dioxides with extrusion of sulfur
dioxide;25 and (v) substitution of a â-functional group,
such as alkylthio,26 imidazolyl,27 and methoxy.28 Oxida-
tive cleavage of pyridinium perchlorates with hydrogen
(12) Kolos, N. N.; Orlov, V. D.; Yuzefovskaya E. Ya.; Yaremenko,
F. G.; Vorob’eva, N. P.; Shishkin, O. V.; Struchkov, Yu. T.; Ivkov, S.
M. Chem. Heterocycl. Compd. (Engl. Transl.) 1995, 31, 827.
(13) Gielen, H.; Li, V. M.-J .; Rosentreter, U.; Schlemmer, K.-H.;
Fitzgerald, M.; Nash, K. Br. Pat. GB 2383326 A, 2003; Chem. Abstr.
2003, 139, 490839.
(14) Mukhanova, T. I.; Alekseeva, L. M.; Granik, V. G. Chem.
Heterocycl. Compd. (Engl. Transl.) 2002, 38, 586.
(15) Sakamoto, T.; Nagano, T.; Kondo, Y.; Yamanaka, H. Synthesis
1990, 215.
(1) Bonnett, R. In The Chemistry of the Carbon-Nitrogen Double
Bond; Patai, S., Eds.; Interscience Publishers: London, 1970; p 597.
(2) (a) Paul, H.; Weise, A.; Dettmer, R. Chem. Ber. 1965, 98, 1450.
(b) Kotali, A.; Lafazanis, I. S. Arkivoc 2003, vi, 91.
(16) Bunnelle, W. H.; Singam, P. R.; Narayanan, B. A.; Bradshaw,
C. W.; Liou, J . S. Synthesis 1997, 439.
(3) (a) Schulenberg, J . W.; Archer, S. J . Am. Chem. Soc. 1960, 82,
2035. (b) Rowe, J . E. Synthesis 1980, 114.
(17) Charushin, V. N.; Mochulskaya, N. N.; Andreiko, A. A.; Filya-
kova, V. I.; Kodess, M. I.; Chupakhin, O. N. Tetrahedron Lett. 2003,
44, 2421.
(18) Bratusˇek, U.; Meden, A.; Svete, J .; Stanovnik, B. Arkivoc 2003,
v, 77.
(19) (a) Alberola, A.; Calvo, L. A.; Ortega, A. G.; Ru´ız, M. C. S.;
Yustos, P.; Granda, S. G.; Garc´ıa-Rodriguez, E. J . Org. Chem. 1999,
64, 9493. (b) Savarin, C. G.; Murry, J . A.; Dormer, P. G. Org. Lett.
2002, 4, 2071.
(4) (a) Ley, H. Chem. Ber. 1898, 31, 240. (b) Ley, H. Chem. Ber. 1901,
34, 2620. (c) Houghton, P. G.; Pipe, D. F.; Rees, C. W. J . Chem. Soc.,
Perkin Trans. 1 1985, 1471. (d) Romine, J . L.; Martin, S. W.; Gribkoff,
V. K.; Boissard, C. G.; Dworetzky, S. I.; Natale, J .; Li, Y.; Gao, Q.;
Meanwell, N. A.; Starrett, J . E., J r. J . Med. Chem. 2002, 45, 2942.
(5) (a) Clark, N. G.; Cawkill, E. Tetrahedron Lett. 1975, 2717. (b)
Smith, J . G.; Irwin, D. C. Synthesis 1978, 894.
(6) (a) Leo, H. Chem. Ber. 1877, 10, 2133. (b) Barnikow, G.; Lehner,
J . Z. Chem. 1990, 30, 89.
(7) Quast, H.; Frank, R.; Heublein, A.; Schmitt, E. Liebigs Ann.
Chem. 1979, 83.
(8) (a) Katritzky, A. R.; Rachwal, S.; Offerman, R. J .; Najzarek, Z.;
Yagoub, A. K.; Zhang, Y. Chem. Ber. 1990, 123, 1545. (b) Katritzky,
A. R.; Stevens, C. V.; Zhang, G.-F.; J iang, J . Heterocycles 1995, 40,
231. (c) Katritzky, A. R.; Yang, B.; Abonia, R.; Insuasty, B. J . Chem.
Res., Synop. 1996, 540. (d) Katritzky, A. R.; Button, M. A. C.; Busont,
S. J . Org. Chem. 2001, 66, 2865. (e) Katritzky, A. R.; Donkor, A.; Fang,
Y. J . Org. Chem. 2001, 66, 4041.
(20) (a) Sinsky, M. S.; Bass, R. G. J . Heterocycl. Chem. 1984, 21,
759. (b) Liu, Y.; Yu, C.-Y.; Wang, M.-X. Arkivoc 2003, ii, 146.
(21) (a) Gilchrist, T. L.; Iskander, G. M. J . Chem. Soc., Perkin Trans.
1 1982, 831. (b) Saeed, A. A. H. J . Chem. Eng. Data 1984, 29, 358. (c)
Valduga, C. J .; Squizani, A.; Braibante, H. S.; Braibante, M. E. F.
Synthesis 1998, 1019.
(22) (a) Bol’shedvorskaya, R. L.; Pavlova, G. A.; Gavrilov, L. D.;
Alekseeva, N. V.; Vereshchagin, L. I. J . Org. Chem. USSR (Engl.
Transl.) 1972, 8, 1927. (b) Korshunov, S. P.; Korzhova, N. V.;
Kazantseva, V. M.; Krasnov, V. L.; Utekhina, N. V.; Bodrikov, I. V. J .
Org. Chem. USSR (Engl. Transl.) 1986, 22, 1658.
(23) Bozell, J . J .; Hegedus, L. S. J . Org. Chem. 1981, 46, 2561.
(24) Seko, S.; Tani, N. Tetrahedron Lett. 1998, 39, 8117.
(25) Hofsløkken, N. U.; Skattebøl, L. J . Chem. Soc., Perkin Trans.
1 1999, 3085.
(9) Katritzky, A. R.; Monteux, D. A.; Tymoshenko, D. O. Org. Lett.
1999, 1, 577.
(10) Katritzky, A. R.; Huang, T.-B.; Voronkov, M. V. J . Org. Chem.
2001, 66, 1043.
(11) Lue, P.; Greenhill, J . V. Adv. Heterocycl. Chem. 1996, 67, 207.
(26) Nishio, T.; Omote, Y. Synthesis 1980, 390.
10.1021/jo0496594 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/19/2004
5108
J . Org. Chem. 2004, 69, 5108-5111

SCHEME 2
new approach makes a variety of imidoylbenzotriazoles
readily available by a simple procedure in good yields.
We also report the synthesis of enaminones 6a -h via
substitution of the benzotriazolyl group in imidoylben-
zotriazoles 3a ,b,e,g with silyl enol ethers 5a ,b (Scheme
3, Table 2): this represents a convergent synthesis of
enaminones in which bond b is formed.
P r ep a r a tion of Im id oylben zotr ia zoles (3). Second-
ary amides 2a -i were treated with a mixture of 1-chloro-
1H-benzotriazole and triphenylphosphine in THF under
reflux to give the corresponding imidoylbenzotriazoles
3a -i in good yields (Scheme 1, Table 1). Structures 3a -i
are supported by their 1H NMR and 13C NMR spectra.
1
The H NMR spectra of 3a -i showed the appearance of
a new set of signals at 7.3-8.6 ppm, characteristic of the
benzotriazolyl group.8,9,10 The 13C NMR spectra of 3a -i
also showed the disappearance of the amide signals and
the appearance of the new signals around 115, 120, 124,
127, 131, and 146 ppm, corresponding to the N-substi-
tuted benzotriazoles, and at 153-155 ppm, corresponding
to the imine carbon.8,9,10
peroxide (route xi)29 provides enaminones via bond d .
However, the formation of bonds a and d shows limited
convergence as the “enaminone carbon skeleton” is part
of a starting material and this limits the selective
construction of unsymmetrical enaminones. Therefore the
preparation of enaminones via formation of b or c
carbon-carbon bond is frequently preferable. For the
preparation via bond b, the following approaches are
available: (vi) coupling of silyl enol ethers with oxime
sulfonates;30 (vii) reaction of imidoyl chlorides with
acetonyltributyltin in the presence of palladium cata-
lyst,31 (viii) similar reaction with enolates of ketones;32
and (ix) reactions of nitriles with ketones in the presence
of base.33 Existing methods (vi-ix) for construction of
bond b show some limitations: (a) the oxime route (vi)
involves a C f N migration and is limited to symmetric
oximes;30 (b) for imidoyl chlorides (routes vii-viii), a low
yield and formation of byproduct in a reaction with
acetonyltributyltin (single example)31 was reported and
the reaction with enolates was described only for fluori-
nated imidoyl chlorides;32 (c) reactions of nitriles with
ketones (route ix) were described only for nitriles of
aromatic33a and fluorinated33b acids. The only approach
presently available for the synthesis of diverse enami-
nones in good yields is route (x): the reaction of ketimine
anions with esters16,32,34 or acylbenzotriazoles,35 in which
bond c is formed.
P r ep a r a tion of En a m in ok eton es (6) fr om Im i-
d oylb en zot r ia zoles (3). Imidoylbenzotriazoles 3a ,b
were reacted with enolates generated from corresponding
ketones 4a ,b by treatment with base. Previously inves-
tigated reactions of imidoylbenzotriazoles with 2-methyl-
2-oxazoline and 2-methyl-2-thiazoline in the presence of
LDA or n-BuLi gave products of substitution in high
yields and demonstrated the stability of imidoylbenzo-
triazoles in the presence of strong bases at low tempera-
tures.8e Reactions of compounds 3a ,b with ketones 4a ,b
in the presence of LDA (2.0-2.5 equiv) at temperatures
ranging from -78 to 0 °C resulted in condensation of the
ketones and recovery of the imidoylbenzotriazoles 3a ,b.
Treatment of 3b with ketones 4a ,b (2 equiv) in the
presence of potassium tert-butoxide (2.5-3.0 equiv) in
THF or diethyl ether at temperatures from 0 to 40 °C
(reflux in diethyl ether) gave enaminoketones 6c,d in low
yields (20-30%). The major byproduct of these reactions
was the corresponding amide 2b. The formation of 2b is
ascribed to the hydrolysis of 3b in the presence of a strong
base. Water is formed from the aldol condensation of
ketones, resulting in the hydrolysis of 3b. Generally,
higher rates of these reactions were observed at higher
temperatures with similar selectivity.
On the other hand, treatment of 3a ,b,e,g with silyl enol
ethers 5a ,b (2-2.5 equiv) in the presence of potassium
tert-butoxide (2.5-3.0 equiv) in THF at temperatures
from 20 to 40 °C or in diethyl ether at 20-35 °C gave
enaminoketones 6a -h in good yields (Scheme 3, Table
2). The major byproducts observed in these reactions
were the corresponding amides 2a ,b,e,g.
We now disclose the one-step preparation of imidoyl-
benzotriazoles 3a -i by reactions of secondary amides
2a -i with 1-chloro-1H-benzotriazole in the presence of
triphenylphosphine (Scheme 1, route vi, Table 1). This
(27) Kashima, C.; Tajima, T.; Shimizu, M.; Omote, Y. J . Heterocycl.
Chem. 1982, 19, 1325.
(28) Okubo, M.; Nakagawa, Y.; Yoshida, M.; Yanase, H. Bull. Chem.
Soc. J pn. 1985, 58, 2707.
(29) Katritzky, A. R.; Ramsden, C. A.; Zakaria, Z.; Harlow, R. L.;
Simonsen, S. H. J . Chem. Soc., Perkin Trans. 1 1980, 1870.
(30) Matsumura, Y.; Fujiwara, J .; Maruoka, K.; Yamamoto, H. J .
Am. Chem. Soc. 1983, 105, 6312.
(31) Kosugi, M.; Koshiba, M.; Atoh, A.; Sano, H.; Migita, T. Bull.
Chem. Soc. J pn. 1986, 59, 677.
(32) Fustero, S.; Garc´ıa de la Torre, M.; Pina, B.; Fuentes, A. S. J .
Org. Chem. 1999, 64, 5551.
(33) (a) Sosnovskikh, V. Ya.; Kostrikova, T. P. Zh. Org. Khim. 1986,
22, 883. (b) Lee, L. F.; Sing, Y. L. J . Org. Chem. 1990, 55, 380.
(34) Bartoli, G.; Cimarelli, C.; Palmieri, G.; Bosco, M.; Dalpozzo, R.
Synthesis 1990, 895.
1
Structures 6a -h were supported by their H and 13C
1
NMR spectra. Their H NMR spectra no longer showed
distinctive signals in the range 7.0-8.2 ppm correspond-
ing to the benzotriazolyl group in 3a ,b,e,g.8,9,10 The
singlets at 12.9-13.10 ppm and at 13.74-14.18 ppm in
the 1H NMR spectra of 6a ,c,e,g and 6b,d ,f,h , respec-
tively, were assigned to the NH proton. The singlets at
5.81-6.08 ppm in the spectra of 6a ,c,e,g were assigned
to olefinic proton. For 6b,d ,f,h , the new set of signals that
(35) Katritzky, A. R.; Fang, Y.; Donkor, A.; Xu, J . Synthesis 2000,
2029.
J . Org. Chem, Vol. 69, No. 15, 2004 5109

TABLE 1. P r ep a r a tive Yield s of Im id oylben zotr ia zoles 3a -i: Com p a r ison w ith P r eviou s Meth od s
a
Corresponding methods for the preparation in Scheme 1.
SCHEME 3
unsymmetrical â-enaminoketones, unavailable by other
methods.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of Im id oylben -
zotr ia zoles 3a -i. To a stirred solution of triphenylphosphine
(524 mg, 2 mmol) in THF (20 mL) was added 1-chloro-1H-
benzotriazole (307 mg, 2 mmol) at room temperature, and the
reaction mixture was stirred for 1 h. The corresponding second-
ary amide 2a -i (1 mmol) was added to the reaction mix-
ture which was then heated under reflux for 20 h. Progress of
the reaction was monitored by TLC; the addition of extra tri-
phenylphosphine and 1-chloro-1H-benzotriazole may be re-
quired. After the starting amide 2a -i had been consumed, the
solvent was evaporated under reduced pressure, and the residue
was purified by flash column chromatography on silica gel (for
3f, on alumina) using hexanes/ethyl acetate gradients to give
3a -i.
N-[Ben zotr ia zol-1-yl(p h en yl)m eth ylid en e]a n ilin e (3a ):
yellow microcrystals from ethyl acetate/hexanes (90%); mp
130-131 °C (lit.8b 130-132 °C); 1H NMR δ 8.48 (d, J ) 8.1 Hz,
1H), 8.14 (d, J ) 8.1 Hz, 1H), 7.65-7.59 (m, 1H), 7.53-7.48 (m,
1H), 7.42-7.35 (m, 5H), 7.25-7.20 (m, 2H), 7.06-7.01 (m, 1H),
6.85 (d, J ) 7.8 Hz, 2H); 13C NMR δ 115.3, 120.0, 121.5, 124.2,
125.6, 128.2, 128.8, 129.3, 130.1, 130.2, 130.4, 132.1, 146.4, 147.0,
153.8.
TABLE 2. P r ep a r a tion of En a m in ok eton es 6a -h
R1
R2
R3
R4
Ph
-(CH2)4-
Ph
3b 6d 4-Me-C6H4 4-MeO-C6H4 -(CH2)4-
yield of 6, %
3a 6a Ph
3a 6b Ph
Ph
Ph
H
80
54
58
65
55
36
40
19
3b 6c 4-Me-C6H4 4-MeO-C6H4
H
3e 6e Bn
3e 6f Bn
3g 6g Me
3g 6h Me
4-Me-C6H4
4-Me-C6H4
Ph
H
Ph
-(CH2)4-
Ph
-(CH2)4-
H
Ph
1
appeared in their H NMR spectra in the ranges 1.53-
1.82 ppm, 2.11-2.28 ppm, and 2.38-2.51 ppm were
assigned to aliphatic protons of the cyclohexanone ring.
The 13C NMR spectra of 6a ,c,e,g showed new signals at
188.6-189.6 ppm as well as at 94.2-97.0 ppm and
161.4-164.6 ppm, corresponding to carbonyl carbon and
the vinyl fragment of 6a ,c,e,g, respectively. Similarly,
the 13C NMR spectra of 6b,d ,f,h showed new signals at
196.0-199.0 ppm and at 159.5-161.2 ppm, correspond-
ing to carbonyl carbon and the vinyl carbon next to
amine, respectively. Unlike 3a ,c,e,g, the 13C NMR spec-
tra of 6a -h no longer showed either the characteristic
benzotriazole signals around 115, 120, and 146 ppm or
the imine carbon signal at 153-155 ppm.
N-[Ben zot r ia zol-1-yl(4-m et h ylp h en yl)m et h ylid en e]-4-
m eth oxya n ilin e (3b): yellow plates from methylene chloride
1
(75%); mp 71-73 °C (lit.8e mp 56-58 °C); H NMR δ 8.43 (d, J
) 8.2 Hz, 1 H), 8.14 (d, J ) 8.2 Hz, 1H), 7.64-7.46 (m, 2H),
7.29-7.17 (m, 5H), 6.83-6.76 (m, 4H), 3.77 (s, 3H), 2.38 (s, 3H);
13C NMR δ 21.6, 55.4, 114.1, 115.3, 119.9, 122.4, 123.0, 125.3,
127.6, 129.0, 129.0, 130.1, 132.1, 140.1, 140.6, 146.3, 153.2, 156.5.
Anal. Calcd for C21H18N4O: C, 73.67; H, 5.30; N, 16.36. Found:
C, 73.55; H, 5.29; N, 16.67.
N-[1-(Ben zotr ia zol-1-yl)-2-p h en yleth ylid en e]-4-m eth yl-
a n ilin e (3e): white microcrystals from methylene chloride
(83%); mp 123-125 °C; 1H NMR δ 8.52 (d, J ) 8.2 Hz, 1H), 8.08
(d, J ) 8.2 Hz, 1H), 7.60-7.55 (m, 1H), 7.48-7.42 (m, 1H), 7.22-
7.13 (m, 7H), 6.87 (d, J ) 8.2 Hz, 2H), 4.61 (s, 2H), 2.38 (s, 3H);
13C NMR δ 20.9, 34.7, 115.6, 119.7, 120.1, 125.4, 126.8, 128.6,
128.7, 129.2, 129.8, 131.5, 134.0, 135.3, 144.4, 146.6, 154.6. Anal.
Calcd for C21H18N4: C, 77.28; H, 5.56; N, 17.17. Found: C, 77.39;
H, 5.55; N, 17.44.
N-[1-(Ben zotr ia zol-1-yl)eth ylid en e]a n ilin e (3g): white
microcrystals from ethyl acetate/hexanes (90%); mp 106-107 °C
(lit.9 mp 107-108 °C); 1H NMR δ 8.54 (d, J ) 8.4 Hz, 1H), 8.13
(d, J ) 8.4 Hz, 1H), 7.62-7.57 (m, 1H), 7.50-7.40 (m, 3H), 7.22-
7.17 (m, 1H), 6.95 (d, J ) 7.4 Hz, 2H), 2.75 (s, 3H); 13C NMR δ
16.1, 115.6, 119.6, 120.1, 124.2, 125.2, 129.1, 129.1, 131.1, 146.5,
147.2, 153.8.
An efficient and simple route to imidoylbenzotriazoles
has been developed using secondary amides and 1-chloro-
1H-benzotriazole. The procedure uses no aggressive
reagents and occurs under mild reaction conditions. This
method provides easy access to imidoylbenzotriazoles
3a -i in good yields and complements previous prep-
arations of imidoylbenzotriazoles. The reaction of imi-
doylbenzotriazoles with silyl enolates opens a new way
for the synthesis of â-enaminoketones; it is especially
useful as a synthetic method for the preparation of
5110 J . Org. Chem., Vol. 69, No. 15, 2004

Gen er a l P r oced u r e for th e P r ep a r a tion of En a m in ok e-
ton es 6a -h . To a stirred solution of the corresponding imidoyl-
benzotriazole 3a ,b,e,g (1 mmol) in THF or diethyl ether (20 mL),
the corresponding silyl enol ether 5a ,b (2-2.5 mmol) and then
potassium tert-butoxide (0.28-0.34 g, 2.5-3.0 mmol) were added
at room temperature. The reaction mixture was stirred for 12-
40 h either at room temperature (if THF was used as solvent)
or while refluxing (if diethyl ether was used as solvent). Progress
of the reaction was monitored by TLC. After the reaction was
complete, water (40 mL) was added to the reaction mixture,
which was then extracted with diethyl ether (5 × 25 mL). The
combined extracts were dried over anhydrous magnesium
sulfate. The solvent was removed under reduced pressure and
the remaining residue was purified by gradient column chro-
matography on silica gel (hexanes-ethyl acetate/hexanes 1:15)
to give 6a -h .
2-[(4-Meth oxya n ilin o)(4-m eth ylp h en yl)m eth ylid en e]cy-
cloh exa n on e (6d ): yellow-orange microcrystals from methyl-
ene chloride (28%); mp 119-121 °C; 1H NMR δ 13.78 (s, 1H),
7.12 (d, J ) 7.8 Hz, 2H), 7.03 (d, J ) 7.8 Hz, 2H), 6.62-6.55 (m,
4H) 3.68 (s, 3H), 2.47 (t, J ) 6.7 Hz, 2H), 2.33 (s, 3H), 2.11 (t, J
) 6.2 Hz, 2H), 1.79-1.70 (m, 2H), 1.60-1.54 (m, 2H); 13C NMR
δ 21.3, 22.7, 24.0, 27.4, 38.4, 55.2, 102.9, 113.7, 124.8, 128.5,
129.1, 131.3, 132.9, 138.3, 156.0, 160.8, 198.1. Anal. Calcd for
C21H23NO2: C, 78.47; H, 7.21; N, 4.36. Found: C, 78.00; H, 7.52;
N, 3.98.
1,4-Dip h en yl-3-(4-tolu id in o)-2-bu ten -1-on e (6e): yellow
microcrystals from diethyl ether (55%); mp 87-89 °C; 1H NMR
δ 13.05 (s, 1H), 7.85-7.82 (m, 2H), 7.44-7.35 (m, 3H), 7.28-
7.20 (m, 3H), 7.14-7.08 (m, 4H), 6.98 (d, J ) 8.2 Hz, 2H), 5.81
(s, 1H), 3.72 (s, 2H), 2.32 (s, 3H); 13C NMR δ 20.9, 38.5, 94.3,
125.5, 126.7, 127.0, 128.2, 128.5, 128.8, 129.6, 130.8, 135.5, 136.0,
136.7, 140.0, 164.6, 188.8. Anal. Calcd for C23H21NO: C, 84.37;
H, 6.46; N, 4.28. Found: C, 84.49; H, 6.64; N, 4.28.
3-An ilin o-1,3-d ip h en yl-2-p r op en -1-on e (6a ):
yellow-
orange microcrystals from methylene chloride (80%); mp 95-
1
97 °C (lit.26 mp 101-102 °C); H NMR δ 12.90 (s, 1H), 7.96 (d,
2-[2-P h en yl-1-(4-tolu idin o)eth yliden e]cycloh exan on e (6f):
orange oil (36%); 1H NMR δ 14.17 (s, 1H), 7.31-7.19 (m, 3H),
7.12 (d, J ) 6.9 Hz, 2H), 7.01 (d, J ) 8.2 Hz, 2H), 6.88 (d, J )
8.2 Hz, 2H), 3.75 (s, 2H), 2.44 (t, J ) 6.6 Hz, 2H), 2.28-2.21 (m,
5H), 1.75-1.67 (m, 2H), 1.65-1.57 (m, 2H); 13C NMR δ 20.8,
22.7, 23.8, 25.7, 34.2, 38.1, 102.9, 125.0, 126.4, 127.7, 128.7,
J ) 6.9 Hz, 2H), 7.50-7.26 (m, 8H), 7.14-7.08 (m, 2H), 7.00-
6.94 (m, 1H), 6.78 (d, J ) 8.0 Hz, 2H), 6.08 (s, 1H); 13C NMR δ
97.0, 123.1, 124.1, 127.2, 128.3, 128.5, 128.7, 129.6, 131.3, 135.8,
139.4, 139.8, 161.4, 189.6. Anal. Calcd for C21H17NO: C, 84.25;
H, 5.72; N, 4.68. Found: C, 84.50; H, 5.86; N, 4.30.
2-[An ilin o(p h en yl)m eth ylid en e]cycloh exa n on e (6b): yel-
low microcrystals from methylene chloride (54%); mp 125-127
129.6, 135.5, 136.0, 136.6, 161.5, 196.8. Anal. Calcd for C21H23
-
NO: C, 82.58; H, 7.59; N, 4.59. Found: C, 82.21; H, 7.95; N,
4.25.
1
°C (lit.36 mp 135-136 °C); H NMR δ 13.74 (s, 1H), 7.35-7.30
(m, 3H), 7.20-7.16 (m, 2H), 7.06-6.97 (m, 2H), 6.91-6.85 (m,
1H), 6.61 (d, J ) 8.0 Hz, 2H), 2.51-2.44 (m, 2H), 2.13 (t, J )
6.3 Hz, 2H), 1.82-1.71 (m, 2H), 1.63-1.53 (m, 2H); 13C NMR δ
22.6, 23.9, 27.4, 38.5, 103.7, 122.9, 123.5, 128.4, 128.5, 128.6,
134.2, 139.7, 142.2, 159.5, 199.0. Anal. Calcd for C19H19NO: C,
82.28; H, 6.90; N, 5.05. Found: C, 81.91; H, 7.24; N, 4.81.
3-(4-Meth oxyan ilin o)-3-(4-m eth ylph en yl)-1-ph en yl-2-pr o-
p en -1-on e (6c): yellow-orange microcrystals from methylene
chloride (58%); mp 126-128 °C; 1H NMR δ 12.90 (s, 1H), 7.99-
7.91 (m, 2H), 7.50-7.37 (m, 3H), 7.26 (d, J ) 8.0 Hz, 2H), 7.11
(d, J ) 7.7 Hz, 2H), 6.76 (d, J ) 8.8 Hz, 2H), 6.68 (d, J ) 9.1 Hz,
2H), 6.03 (s, 1H), 3.71 (s, 3H), 2.34 (s, 3H); 13C NMR δ 21.3,
55.3, 95.9, 113.9, 124.8, 127.1, 128.3, 128.4, 129.1, 131.0, 132.6,
3-An ilin o-1-p h en yl-2-bu ten -1-on e (6g): orange microcrys-
tals from diethyl ether (42%); mp 104-106 °C (lit.26 mp 105-
1
106 °C); H NMR δ 13.10 (br s, 1H), 7.93-7.90 (m, 2H), 7.46-
7.39 (m, 3H), 7.35 (d, J ) 8.0 Hz, 2H), 7.24-7.16 (m, 3H), 5.89
(s, 1H), 2.14 (s, 3H); 13C NMR δ 20.4, 94.2, 124.8, 125.7, 127.0,
128.2, 129.1, 130.9, 138.6, 140.0, 162.2, 188.7.
2-[1-An ilin oeth ylid en e]cycloh exa n on e (6h ): yellow oil21b
(19%); 1H NMR δ 14.06 (s, 1H), 7.37-7.31 (m, 2H), 7.19 (t, J )
7.4 Hz, 1H), 7.08 (d, J ) 7.7 Hz, 2H), 2.42-2.37 (m, 4H), 1.99
(s, 3H), 1.77-1.72 (m, 4H); 13C NMR δ 16.2, 22.8, 23.9, 26.5,
38.2, 102.8, 125.2, 125.4, 129.0, 139.1, 160.5, 196.0.
132.8, 139.7, 140.1, 156.4, 162.2, 189.1. Anal. Calcd for C23H21
NO2: C, 80.44; H, 6.16; N, 4.08. Found: C, 80.53; H, 6.42; N,
3.98.
-
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for imidoylbenzotriazoles 3c,d ,f,h ,i. This material is
available free of charge via the Internet at http://pubs.acs.org.
(36) Sekiya, M.; Morimoto, T. Chem. Pharm. Bull. 1975, 23, 1241.
J O0496594
J . Org. Chem, Vol. 69, No. 15, 2004 5111