General and Efficient Insertion of Carbons Carrying Benzotriazole

Article abstract of DOI:10.1021/jo035098p

Anions formed from the lithiation of 1-(1-benzotriazolylalkyl)benzotriazoles (1, 6) and 1-(1-methylthioalkyl)benzotriazoles (10 and 10a) with n-BuLi underwent additions to cyclic and acyclic ketones giving intermediates 3a-f, 7b-f, and 11b-d, respectively

Full text of DOI:10.1021/jo035098p

Gen er a l a n d Efficien t In ser tion of Ca r bon s Ca r r yin g
Ben zotr ia zole
Alan R. Katritzky,* Sergey Bobrov, Kostyantyn Kirichenko, and Yu J i
Center for Heterocyclic Compounds, University of Florida, Department of Chemistry,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received J uly 28, 2003
Anions formed from the lithiation of 1-(1-benzotriazolylalkyl)benzotriazoles (1, 6) and 1-(1-
methylthioalkyl)benzotriazoles (10 and 10a ) with n-BuLi underwent additions to cyclic and acyclic
ketones giving intermediates 3a -f, 7b-f, and 11b-d , respectively, in excellent yields. Thermal
rearrangements of intermediates 3a ,b,d -f and 7b-d ,f in the presence of zinc bromide provided
one-carbon chain-extended or ring-expanded R-benzotriazolyl ketones 4a ,b,d -f and 8b-d ,f in
moderate yields with excellent regioselectivity. By contrast, intermediates 11b-d on treatment
with zinc bromide loose a molecule of benzotriazole followed by intramolecular cyclization of the
resulting intermediates 12b-d to provide the 2,3- and 1,2,3-substituted indenes 13b-d in good
yields.
SCHEME 1
In tr od u ction
The homologation of aldehydes and ketones is an
important transformation in modern synthetic organic
chemistry that has been extensively investigated. Pub-
lished procedures for the insertions of a single carbon
next to a carbonyl group have been summarized in
several reviews1 and in our recent publications.2 These
published results (Scheme 1) can be classified as fol-
lows: (i) insertion by diazo compounds;1d-f,3 (ii) insertion
via â-oxido carbenoid intermediates generated from di-
bromomethane4 or dichloromethane;5 (iii) insertions uti-
lizing R-lithioalkyl sulfoxide,6 selenoxide,6,7 R-lithioalkyl
sulfones,8 or selenones;9 (iv) rearrangement of a 2-ben-
zotriazolylalkoxide.2,10
Recent work in our group achieved good regioselectivity
in the simultaneous homologation and R-functionaliza-
tion of ketones and aldehydes via benzotriazole interme-
diates.2 In particular, various alkyl, aryl, heteroaryl,
alkoxy, and aryloxy substituents were thus introduced.
The present manuscript deals with the insertions of
carbon carrying a benzotriazolyl substituent to give
R-benzotriazolyl ketones as products. Such ketones with
an R-benzotriazolyl group are of significant synthetic
utility for transformations to (i) diketones,11 (ii) olefins,12
(iii) for directed regioselective R-alkylation,13 and (iv)
heterocycle ring synthesis (Scheme 2).14
(1) (a) Gutsche, C. D. Org. React. 1954, 364. (b) Smith, P. A. S.; Baer,
D. R. Org. React. 1960, 157. (c) Gutsche, C. D.; Redmore, D. Carbocyclic
Ring Expansion Reactions; Academic Press: New York, 1968; Chapter
4, p 81. (d) Cowell, G. W.; Ledwith, A. Q. Rev. 1970, 24, 119. (e) Pizey,
J . S. Synth. Reagents 1974, 2, 102. (f) Krow, G. R. Tetrahedron 1987,
43, 3.
(2) (a) Katritzky, A. R.; Xie, L.; Toader, D.; Serdyuk, L. J . Am. Chem.
Soc. 1995, 117, 12015. (b) Katritzky, A. R.; Yang, Z.; Moutou, J .-L.
Tetrahedron Lett. 1995, 36, 841. (c) Katritzky, A. R.; Xie, L.; Serdyuk,
L. J . Org. Chem. 1996, 61, 7564. (d) Katritzky, A. R.; Toader, D.; Xie,
L. J . Org. Chem. 1996, 61, 7571.
(3) (a) Mock, W. L.; Hartman, M. E. J . Org. Chem. 1977, 42, 459.
(b) Hashimoto, N.; Aoyama, T.; Shioiri, T. Tetrahedron Lett. 1980, 21,
4619. (c) Loeschorn, C. A.; Nakajima, M.; McCloskey, P. J .; Anselme,
J .-P. J . Org. Chem. 1983, 48, 4407. (d) Holmquist, C. R.; Roskamp, E.
J . J . Org. Chem. 1989, 54, 3258. (e) Maruoka, K.; Concepcion, A. B.;
Yamamoto, H. J . Org. Chem. 1994, 59, 4725.
(4) (a) Taguchi, H.; Yamamoto, H.; Nozaki, H. J . Am. Chem. Soc.
1974, 96, 6510. (b) Taguchi, H.; Yamamoto, H.; Nozaki, H. Tetrahedron
Lett. 1976, 30, 2617.
Our present investigations have led to regioselective
R-carbon insertions into ketones 2a -f (Schemes 3 and
(10) Katritzky, A. R.; Zhang, Z.; Lang, H.; Xie, L. Heterocycles 1998,
47, 187.
(11) (a) Katritzky, A. R.; Kuzmierkiewicz, W. V. J . Chem. Soc.,
Perkin Trans. 1 1987, 819. (b) Katritzky, A. R.; Wang, Z.; Lang, H.;
Feng, D. J . Org. Chem. 1997, 62, 4125.
(5) Villieras, J .; Perriot, P.; Normant, J . F. Synthesis 1979, 968.
(6) Gadwood, R. C.; Mallick, I. M.; DeWinter, A. J . J . Org. Chem.
1987, 52, 774.
(7) Gadwood, R. C. J . Org. Chem. 1983, 48, 2098.
(8) (a) Trost, B. M.; Mikhail, G. K. J . Am. Chem. Soc. 1987, 109,
4124. (b) Phillipson, N.; Anson, M. S.; Montana, J . G.; Taylor, R. J . K.
J . Chem. Soc., Perkin Trans. 1 1997, 19, 2821.
(9) Krief, A.; Dumont, W.; Laboureur, J . L.. Tetrahedron Lett. 1988,
29, 3265.
(12) (a) Katritzky, A. R.; Fali, C. N.; Li, J . J . Org. Chem. 1997, 62,
4148. (b) Katritzky, A. R.; Voronkov, M. V.; Toader, D. J . Chem. Soc.,
Perkin Trans. 2 1998, 2515. (c) Katritzky, A. R.; Cheng, D.; Li, J . J .
Org. Chem. 1998, 63, 3438. (d) Katritzky, A. R.; Toader, D.; Chassaing,
C. J . Org. Chem. 1998, 63, 9983.
10.1021/jo035098p CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/25/2003
J . Org. Chem. 2004, 69, 303-308
303

Katritzky et al.
TABLE 1. P r ep a r a tion of In ter m ed ia tes 3 a n d
r-Ben zotr ia zolyl Keton es 4
SCHEME 2
2
yield, %/solvent/time, h
R1
R2
Bn
Ph
Ph
3
4
a
b
c
d
e
f
Bn
Me
Ph
-(CH2)4-
-(CH2)5-
Me
60/THF/2
90/THF/2
85/THF/2
60/THF/2
80/THF/2
90/THF/2
54/CHCl2CHCl2/5
75/CHCl2CHCl2/5
-
70/CHCl2CHCl2/5
41/CHCl2CHCl2/5
60/CHCl2CHCl2/5
i-Pr
TABLE 2. P r ep a r a tion of In ter m ed ia tes 7 a n d
r-Ben zotr ia zolyl Keton es 8
2
yield, %/solvent/time, h
R1
R2
Ph
Ph
7
8
b
c
d
e
f
Me
Ph
-(CH2)4-
-(CH2)5-
Me
90/THF/13
70/THF/13
50/THF/13
75/THF/13
80/THF/13
40/CHCl2CHCl2/0.25
55/CH2ClCH2Cl/0.5
35/CHCl2CHCl2/0.25
a
SCHEME 3a
i-Pr
20/CH2ClCH2Cl/4
a
Product 9 was isolated in 40% yield.
reacted sluggishly and apparently reversibly with ke-
tones 2b-f: if the temperature of the reaction mixture
rises to 20 °C prior to quenching with aqueous am-
monium chloride, the starting compound 6 is recovered.
However, keeping the reaction mixture at -78 °C for 12
h followed by quenching with aqueous ammonium chlo-
ride at the same temperature gave 7b-f in high yields
(Scheme 4, Table 2). The structures of compounds 3a -f
a
For designation of R1-R2 see Table 1.
SCHEME 4a
1
and 7b-f were supported by their H NMR and 13C NMR
spectra (see the Experimental Section).
The mechanism of transformation of 3 to 4 and 7 to 8
was explained in our previous publications.2a,c,d The
present rearrangements proceed regioselectively: treat-
ing adducts 3a ,b,d -f and 7b-d ,f in 1,1,2,2-tetrachloro-
ethane or 1,2-dichloroethane under reflux with a 5-fold
excess of zinc bromide afforded the one carbon homolo-
gated ketones 4a,b,d-f and 8b-d,f respectively (Schemes
3 and 4, Tables 1 and 2). In each case, migration occurs
of the carbon that can best stabilize an electron deficiency
in the transition state. In the case of 4a ,b,d -f, the
rearrangement could be completed in refluxing 1,1,2,2-
tetrachloroethane for 5 h (Table 1). By contrast, adduct
3c (Scheme 3) failed to undergo the zinc bromide-
promoted rearrangement in the 1,1,2,2-tetrachloroethane
under reflux for 64 h; under these reaction conditions
(Scheme 3), only the dehydration product 5 was isolated
in 20% yield.
a
For designation of R1-R2 see Table 2.
4) utilizing 1-(1-benzotriazolylalkyl)benzotriazoles 1 and
6. In related work, the use of 1-(1-methylthioalkyl)-
benzotriazoles 10 and 10a led to the 2,3- and 1,2,3-
substituted indenes 13b-d .
Resu lts a n d Discu ssion
We have examined the behavior of 1-(1-benzotriazolyl-
alkyl)benzotriazoles 1 and 6 and 1-(1-methylthioalkyl)-
benzotriazoles 10 and 10a in the one-carbon homologa-
tion of ketones 2a -f and found that reactivity of inter-
mediates 3a -f, 7b-f, and 11b-d varies with the degree
and type of substitution at the R-carbon adjacent to the
benzotriazole group.
The treatment of compound 1 with n-BuLi (1 equiv)
at -78 °C under nitrogen in THF for 1 h followed by
reactions with ketones 2a -f (1 equiv) at -78 °C for 1 h
led to high isolated yields of the corresponding interme-
diates 3a -f (Scheme 3, Table 1). Surprisingly, under the
same reaction conditions, the lithium derivative of 6
We found that the rearrangements of the intermediates
7b-d ,f (Scheme 4, Table 2) required different reaction
temperatures and reaction time to complete the forma-
tion of the corresponding ketones 8b-d ,f. Moreover,
rearrangement of 7b-d ,f generally gave yields of 8b-
d ,f around 20% less as compared to rearrangement of
3a ,b,d -f into 4a ,b,d -f probably due to the concurrent
processes of dehydration and benzotriazole elimination,
as in the case of the transformation of 7e to 9 (Scheme
4). The structures of compounds 4a ,b,d -f, 5, 8b-d ,f, and
1
9 were supported by their H NMR and 13C NMR spectra
(13) Katritzky, A. R.; Wang, Z.; J i, Y.; Fang, Y. J . Arkivoc 2002, iii,
46.
(14) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Tymoshenko, D. O.;
Essawy, S. A. Synthesis 1999, 2114.
(see the Experimental Section).
We have previously demonstrated that 1-[(methylthio)-
methyl]benzotriazole undergoes deprotonation with bu-
304 J . Org. Chem., Vol. 69, No. 2, 2004

Insertion of Carbons Carrying Benzotriazole
TABLE 3. P r ep a r a tion of In ter m ed ia tes 11b-d a n d 12c
a n d Su bstitu ted In d en es 13b-d
tones 2, while in the cases of disubstituted benzotriazolyl
methane derivatives 6, 10, and 10a , either poorer yields
of inserted ketones 8b-d ,f were observed or a different
reaction pathway was involved leading to the formation
of indenes 13b-d .
In summary, an efficient method for the R-carbon
insertions of 1-(1-benzotriazolylalkyl)benzotriazoles into
ketones has been demonstrated. The insertion reactions
take place regioselectively with wide set of cyclic and
acyclic ketones providing both one-carbon chain-extended
and ring-expanded R-benzotriazolyl ketones. In certain
cases, 1-(1-methylthioalkyl)benzotriazoles have been uti-
lized as substrate for the synthesis of 2,3- and 1,2,3-
substituted indenes.
yield, %/solvent/time, h
R
11
12
13
b
c
d
Me
Ph
Ph
81/THF/2
98/THF/2
96/THF/2
a
30/CH2ClCH2Cl/0.1
70/CH2ClCH2Cl/0.1
78/CH2ClCH2Cl/0.1
89/THF/0.25
a
a
Intermediate was not isolated.
SCHEME 5
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on a
hot-stage apparatus and are uncorrected. NMR spectra were
recorded in CDCl3, acetone-d6, or DMSO-d6 with TMS as the
1
internal standard for H (300 MHz) or a solvent as the internal
standard for 13C (75 MHz). THF was dried over sodium/
benzophenone and used freshly distilled. Column chromatog-
raphy was conducted on silica gel 200-425 meshes. (1H-
Benzotriazol-1-ylmethyl)-1H-benzotriazole 1,15 (1H-benzotriazol-
1-ylethyl)-1H-benzotriazole 6,11a and 1-(methylthio)-1-ethyl-
1H-benzotriazole 1016 were prepared according to previously
reported procedures.
Gen er a l P r oced u r e for th e P r ep a r a tion of In ter m ed i-
a tes 3a -f. A solution of dibenzotriazol-1-ylmethane 1 (8.00
mmol) in THF (50 mL) was cooled to -78 °C, and a solution
of n-BuLi (8.80 mmol, 1.58 M in hexane, 5.6 mL) was added
dropwise. The reaction mixture was stirred at the same
temperature for 1 h, and a solution of an appropriate ketone
(8.80 mmol) in THF (15 mL) was added. The mixture was
stirred for an additional 1 h at -78 °C. Then water was added
(30 mL), and the reaction mixture was extracted with diethyl
ether. The extract was dried over anhydrous magnesium
sulfate and evaporated under reduced pressure. The residue
was purified by column chromatography on silica gel to give
3a -f.
tyllithium and that carbanion reacts readily with ali-
phatic and aromatic ketones followed by rearrangement
of the resulting intermediates under zinc bromide ca-
talysis to afford the one-carbon homologated R-(meth-
ylthio)methyl ketones.2c We now show that the 1-(1-
methylthioalkyl)benzotriazoles 10 and 10a similarly
undergo smooth deprotonation with n-BuLi (1 equiv) at
-78 °C under nitrogen in THF for 1 h and the resulting
carbanions react cleanly with ketones 2b,c (1 equiv) at
-78 °C for 1 h giving excellent isolated yields of adducts
(Schemes 5 and 6, Table 3). However, the adducts 11b-d
failed to undergo rearrangement to the R-carbon insertion
products, instead the elimination of benzotriazole was
observed and the 2,3- and 1,2,3-substituted indenes
13b-d were isolated (Schemes 5 and 6, Table 3). In fact,
the adducts 11b-d react with 3-fold excess of zinc
bromide for 15 min in 1,2-dichloromethane at 20 °C
loosing a molecule of benzotriazole providing intermedi-
ates 12b-d which, under reflux in the same solvent for
5 min undergo intramolecular cyclization to give 13b-d
in good yields (Schemes 5 and 6, Table 3). Formation of
12b-d has been established by the isolation of 12c in
89% yield, while 12b was hydrolyzed after aqueous
workup to give 14 in 75% yield.
1,1-Di(1,2,3-ben zotr ia zol-1-yl)-2-ben zyl-3-p h en yl-2-p r o-
p a n ol (3a ): microcrystals from methanol (60%); mp 176-177
°C; 1H NMR (DMSO-d6) δ 8.11 (d, J ) 8.1 Hz, 2H), 7.56-7.39
(m, 6H), 7.34 (s, 1H), 7.18-7.03 (m, 10H), 6.14 (s, 1H), 3.57
(d, J ) 14.0 Hz, 2H), 3.16 (d, J ) 14.0 Hz, 2H); 13C NMR
(DMSO-d6)
126.4, 124.7, 119.5, 110.4, 77.8, 75.2, 42.7. Anal. Calcd for
28H24N6O: C, 73.02; H, 5.25; N, 18.25. Found: C, 73.26; H,
δ 144.8, 135.9, 132.9, 130.4, 128.5, 127.8,
C
5.32; N, 18.45.
(()-1,1-D i(1,2,3-b e n zo t r ia zo l-1-y l)-2-p h e n y l-2-p r o -
p a n ol (3b): microcrystals from methanol (90%); mp 181-182
°C; 1H NMR (DMSO-d6) δ 8.46 (s, 1H), 8.38 (d, J ) 8.5 Hz,
1H), 8.30 (d, J ) 8.5 Hz, 1H), 8.10 (d, J ) 8.3 Hz, 1H), 7.93 (d,
J ) 8.2 Hz, 1H), 7.80-7.68 (m, 2H), 7.68-7.50 (m, 2H), 7.50-
In preceding papers,2a,c,d it was shown that monosub-
stituted benzotriazolylmethanes such as 1-(arylmethyl)-,
1-(heteroarylmethyl)-, 1-(alkenylmethyl)-, 1-(alkoxy-
methyl)-, and 1-[(phenylthio)methyl]benzotriazoles are
excellent insertion reagents for the preparation of R-func-
tionalized ketones. We have now found that (1H-benzo-
triazol-1-ylmethyl)-1H-benzotriazole 1 also behaves in the
same manner undergoing R-carbon insertions into ke-
7.27 (m, 2H), 7.27-7.04 (m, 3H), 6.49 (s, 1H), 1.81 (s, 3H); 13
C
NMR (DMSO-d6) δ 144.8, 144.5, 143.7, 133.1, 132.9, 128.0,
127.7, 127.6, 127.1, 125.5, 124.5, 124.3, 119.1, 118.8, 112.7,
112.6, 77.2, 77.1, 27.5. Anal. Calcd for C21H18N6O: C, 68.09;
H, 4.90; N, 22.69. Found: C, 68.45; H, 5.10; N, 22.56.
SCHEME 6
J . Org. Chem, Vol. 69, No. 2, 2004 305

Katritzky et al.
2,2-Di(1,2,3-b en zot r ia zol-1-yl)-1,1-d ip h en yl-1-et h a n ol
(3c): microcrystals from toluene (85%); mp 231-232 °C; H
(CDCl3) δ 8.07 (d, J ) 8.0 Hz, 1H), 7.47-7.32 (m, 3H), 5.58
(dd, J ) 12.6, 6.3 Hz, 1H), 2.76-2.53 (m, 4H), 2.28-2.16 (m,
2H), 2.04-1.78 (m, 2H); 13C NMR (CDCl3) δ 202.7, 146.1, 132.9,
127.2, 123.8, 120.1, 110.3, 66.6, 41.1, 32.9, 26.8, 24.5. Anal.
Calcd for C12H13N3O: C, 66.96; H, 6.09; N, 19.52. Found: C,
67.13; H, 6.17; N, 19.58. The spectral data of this compound
is identical to that reported in the literature.13
(()-2-(1,2,3-Ben zotr ia zol-1-yl)cycloh ep ta n on e (4e): mi-
crocrystals from methanol (41%); mp 103-104 °C; 1H NMR
(CDCl3) δ 8.05 (d, J ) 8.3 Hz, 1H), 7.50-7.40 (m, 2H), 7.40-
7.30 (m, 1H), 5.73 (dd, J ) 10.3, 3.4 Hz, 1H), 2.85-2.35 (m,
4H), 2.25-1.70 (m, 5H), 1.65-1.50 (m, 1H); 13C NMR (CDCl3)
δ 205.8, 146.1, 132.9, 127.3, 123.8, 120.0, 110.4, 68.1, 41.5, 30.7,
29.3, 27.9, 23.6. Anal. Calcd for C13H15N3O: C, 68.10; H, 6.59;
N, 18.33. Found: C, 68.44; H, 6.61; N, 18.69.
1
NMR (DMSO-d6) δ 9.30 (s, 1H), 8.04 (d, J ) 8.5 Hz, 2H), 7.98
(d, J ) 8.3 Hz, 2H), 7.70 (d, J ) 7.8 Hz, 4H), 7.50 (t, J ) 7.1
Hz, 2H), 7.33 (t, J ) 7.2 Hz, 2H), 7.25-7.10 (m, 6H), 7.01 (s,
1H); 13C NMR (DMSO-d6) δ 144.6, 143.2, 132.6, 128.1, 127.9,
127.3, 125.8, 124.6, 119.2, 111.9, 81.3, 75.5. The spectral data
of this compound is identical to that reported in the litera-
ture.18
1-[Di(1,2,3-b e n zot r ia zol-1-yl)m e t h yl]cyclop e n t a n ol
(3d ): microcrystals from methanol (60%); mp 145-146 °C; 1H
NMR (CDCl3) δ 8.05-8.01 (m, 2H), 7.54-7.49 (m, 3H), 7.40-
7.26 (m, 4H), 4.64 (s, 1H), 2.10-1.75 (m, 8H); 13C NMR (CDCl3)
δ 145.8, 132.3, 128.7, 124.8, 120.0, 110.9, 85.4, 77.7, 38.7, 24.0.
Anal. Calcd for C18H18N6O: C, 64.66; H, 5.43; N, 25.13.
Found: C, 65.03; H, 5.62; N, 25.49.
(()-3-(1,2,3-Ben zotr iazol-1-yl)-4-m eth yl-2-pen tan on e (4f):
1
1-[Di(1,2,3-b e n zot r ia zol-1-yl)m e t h yl]cycloh e xa n ol
oil (60%); H NMR (CDCl3) δ 8.10 (d, J ) 8.2 Hz, 1H), 7.57-
1
(3e): microcrystals from acetone (83%); mp 191-192 °C; H
7.48 (m, 2H), 7.43-7.38 (m, 1H), 5.12 (d, J ) 9.5 Hz, 1H),
3.20-2.98 (m, 1H), 2.10 (s, 3H), 1.12 (d, J ) 6.7 Hz, 3H), 0.80
(d, J ) 6.7 Hz, 3H); 13C NMR (CDCl3) δ 202.5, 146.0, 132.9,
127.9, 124.3, 120.1, 109.9, 73.9, 28.5, 27.5, 19.8, 18.8. Anal.
Calcd for C12H15N3O: C, 66.34; H, 6.96; N, 19.34. Found: C,
65.94; H, 7.14; N, 19.70.
NMR (CDCl3) δ 8.03 (d, J ) 8.2 Hz, 2H), 7.76 (d, J ) 8.4 Hz,
2H), 7.57 (s, 1H), 7.46-7.40 (m, 2H), 7.36-7.31 (m, 2H), 4.64
(s, 1H), 1.86-1.52 (m, 9H), 1.42-1.24 (m,1H); 13C NMR
(CDCl3) δ 145.7, 132.5 128.7, 124.8, 120.0, 111.2, 77.4, 75.6,
34.8, 25.2, 21.2. Anal. Calcd for C19H20N6O: C, 65.50; H, 5.79;
N, 24.12. Found: C, 65.58; H, 5.69; N, 24.39.
1-[1-(1,2,3-Ben zotr ia zol-1-yl)-2,2-d ip h en ylvin yl]-1,2,3-
ben zotr ia zole (5). To a solution of 2,2-di(1,2,3-benzotriazol-
1-yl)-1,1-diphenyl-1-ethanol 3c (1 g, 2.3 mmol) in 1,1,2,2-
tetrachloroethane (20 mL) under nitrogen was added zinc
bromide (3.4 g, 11.6 mmol), and the reaction mixture was
refluxed for 64 h. The reaction mixture was poured into the 1
N aqueous hydrochloric acid and extracted by chloroform. The
chloroform solution was washed with water, dried over potas-
sium carbonate, and evaporated under reduced pressure. The
residue was purified by column chromatography on silica gel
to give the pure product 5 as microcrystals (20%): mp 229-
230 °C; 1H NMR (CDCl3) δ 8.00 (d, J ) 8.0 Hz, 2H), 7.40-
7.27 (m, 6H), 7.17-7.10 (m, 10H); 13C NMR (CDCl3) δ 145.3,
142.1, 136.9, 132.7, 129.2, 129.1, 128.8, 128.5, 124.6, 122.0,
120.2, 109.7. Anal. Calcd for C26H18N6: C, 75.35; H, 4.38; N,
20.28. Found: C, 75.22; H, 4.17; N, 20.40.
Gen er a l P r oced u r e for th e P r ep a r a tion of In ter m ed i-
a tes 7b-f. A solution of 1-[1-(1,2,3-benzotriazol-1-yl)ethyl]-
1,2,3-benzotriazole 6 (7.6 mmol) in THF (50 mL) was cooled
to -78 °C, and a solution of n-BuLi (8.6 mmol, 1.58 M in
hexane, 5.5 mL) was added dropwise. The reaction mixture
was stirred at the same temperature for 1 h, and a solution of
an appropriate ketone (8.3 mmol) in THF (15 mL) was added.
The mixture was stirred for an additional 12 h at -78 °C. Then
water was added (30 mL), and the reaction mixture was
extracted with ether. The extract was dried over anhydrous
magnesium sulfate and evaporated under reduced pressure.
The residue was purified by column chromatography on silica
gel to give 7b-f.
(()-1,1-Di(1,2,3-b en zot r ia zol-1-yl)-2,3-d im et h yl-2-b u -
ta n ol (3f): microcrystals from methanol (90%); mp 178-179
°C; 1H NMR (CDCl3) δ 8.06-7.99 (m, 2H), 7.85 (d, J ) 8.5 Hz,
1H), 7.78 (d, J ) 8.3 Hz, 1H), 7.75 (s, 1H), 7.50-7.26 (m, 4H),
4.77 (s,1H), 2.00-1.82 (m, 1H), 1.20 (s, 3H), 1.10 (d, J ) 6.7
Hz, 3H), 1.04 (d, J ) 6.8 Hz, 3H); 13C NMR (CDCl3) δ 146.1,
145.4, 132.6, 132.3, 129.0, 128.6, 125.0, 124.7, 120.1, 119.9,
111.9, 110.7, 79.6, 75.6, 34.8, 18.2, 18.0, 16.5. Anal. Calcd for
C
18H20N6O: C, 64.27; H, 5.99; N, 24.98. Found: C, 64.72; H,
6.02; N, 25.43.
Gen er a l P r oced u r e for th e In ser tion in to Keton es:
P r ep a r a tion of 4a ,b,d -f. To a solution of an appropriate
intermediate 3a ,b,d -f (3 mmol) in 1,1,2,2-tetrachloroethane
(20 mL) under nitrogen was added zinc bromide (15 mmol),
and the reaction mixture was refluxed for 5 h. The reaction
mixture was poured into the 1 N aqueous hydrochloric acid
and extracted by chloroform. The extract was washed with
water, dried over potassium carbonate and evaporated under
reduced pressure. The residue was purified by column chro-
matography on silica gel to give 4a ,b,d -f.
(()-3-(1,2,3-Ben zot r ia zol-1-yl)-1,4-d ip h en yl-2-b u t a n -
on e (4a ): microcrystals from acetone (54%); mp 106-107 °C;
1H NMR (CDCl3) δ 8.06-7.98 (m, 1H), 7.36-7.26 (m, 2H),
7.18-7.13 (m, 3H), 7.10-7.04 (m, 4H), 6.90-6.85 (m, 4H), 5.67
(dd, J ) 9.8, 5.6 Hz, 1H), 3.72 (dd, J ) 14.2, 5.6 Hz, 1H), 3.65
(d, J ) 15.6 Hz, 1H), 3.55 (d, J ) 15.6 Hz, 1H), 3.50 (dd, J )
14.2, 9.8 Hz, 1H); 13C NMR (CDCl3) δ 201.6, 145.9, 135.8,
133.0, 132.2, 129.1, 128.7, 128.6, 128.5, 127.7, 127.3, 127.0,
124.1, 120.0, 109.3, 67.5, 47.0, 36.1. Anal. Calcd for C22H19
-
(()-3,3-Di(1,2,3-ben zot r ia zol-1-yl)-2-p h en yl-2-b u t a n ol
(7b): microcrystals from methanol (90%); mp 211-212 °C; 1H
NMR (CDCl3) δ 8.10 (d, J ) 8.4 Hz, 1H), 8.00 (d, J ) 8.2 Hz,
1H), 7.30-6.85 (m, 9H), 6.28 (d, J ) 8.4 Hz, 1H), 6.04 (br s,
1H), 5.61 (s, 1H), 2.62 (s, 3H), 2.33 (s, 3H); 13C NMR (CDCl3)
δ 145.8, 1 45.7, 140.6, 133.0, 132.6, 128.5, 128.1, 127.6, 127.6,
126.4, 124.7, 124.3, 120.5, 119.9, 111.2, 111.2, 87.4, 81.7, 26.5,
24.2. Anal. Calcd for C22H20N6O: C, 68.73; H, 5.24; N, 21.86.
Found: C, 68.59; H, 5.36; N, 22.13.
N3O: C, 77.40; H, 5.61; N, 12.31. Found: C, 77.06; H, 5.91; N,
12.35.
(()-1-(1,2,3-Ben zotr iazol-1-yl)-1-ph en ylaceton e (4b): mi-
crocrystals from ether (75%); mp 115-116 °C; 1H NMR (CDCl3)
δ 8.06 (d, J ) 7.3 Hz, 1H), 7.42-7.30 (m, 7H), 7.24-7.21 (m,
1H), 6.75 (s, 1H), 2.34 (s, 3H); 13C NMR (CDCl3) δ 200.5, 146.2,
132.9, 132.2, 129.5, 129.2, 128.9, 127.7, 124.0, 120.1, 110.4,
71.9, 28.1. Anal. Calcd for C15H13N3O: C, 71.70; H, 5.21; N,
16.72. Found: C, 72.05; H, 5.13; N, 16.87.
2,2-D i(1,2,3-b e n zo t r ia zo l-1-y l)-1,1-d ip h e n y l-1-p r o -
p a n ol (7c): microcrystals from methanol (70%); mp 221-222
°C; 1H NMR (CDCl3) δ 8.01 (d, J ) 8.4 Hz, 2H), 7.30-7.00 (m,
14H), 6.42 (d, J ) 6.6 Hz, 2H), 5.68 (s, 1H), 3.14 (s, 3H); 13C
NMR (CDCl3) δ 146.0, 143.0, 133.1, 129.4, 128.3, 127.9, 127.3,
(()-2-(1,2,3-Ben zotr ia zol-1-yl)cycloh exa n on e (4d ): mi-
crocrystals from methanol (70%); mp 129-130 °C; 1H NMR
(15) Avila, L.; Elguero, J .; J ulia´, S.; del Mazo, J . M. Heterocycles
1983, 20, 1787.
124.4, 120.2, 111.4, 87.5, 87.1, 24.6. Anal. Calcd for C27H22
-
(16) Katritzky, A. R.; Oniciu, D. C.; Ghiviriga, I.; Soti, F. J . Org.
Chem. 1998, 63, 2110.
(17) (a) J irkovsky, I.; Cayen, M. N. J . Med. Chem. 1982, 25, 1154.
(b) Enders, D.; Lotter, H. Angew. Chem. 1981, 93, 831.
(18) Katritzky, A. R.; Kavita, M.; Steel, P. J . J . Org. Chem. 2003,
68, 407.
N6O: C, 72.63; H, 4.97; N, 18.82. Found: C, 72.52; H, 5.14; N,
18.76.
1-[1,1-Di(1,2,3-b en zot r ia zol-1-yl)et h yl]cyclop en t a n ol
(7d ): microcrystals from methanol (50%); mp 223-224 °C; 1H
NMR (DMSO-d6) δ 8.08 (d, J ) 8.3 Hz, 2H), 7.29-7.23 (m,
306 J . Org. Chem., Vol. 69, No. 2, 2004

Insertion of Carbons Carrying Benzotriazole
2H), 7.15-7.10 (m, 2H), 6.24 (d, J ) 8.4 Hz, 2H), 5.35 (s, 1H),
2.62 (s, 3H), 2.49-2.33 (m, 2H), 1.90-1.60 (m, 6H); 13C NMR
(DMSO-d6) δ 145.3, 132.4, 127.6, 124.0, 119.4, 111.5, 87.4, 86.8,
37.2, 23.7, 23.6. Anal. Calcd for C19H20N6O: C, 65.50; H, 5.79;
N, 24.12. Found: C, 65.90; H, 6.03; N, 24.60.
1-[1,1-Di(1,2,3-b en zot r ia zol-1-yl)et h yl]cycloh exa n ol
(7e): microcrystals from methanol (75%); mp 249-250 °C; 1H
NMR (DMSO-d6) δ 8.07 (d, J ) 8.2 Hz, 2H), 7.28-7.23 (m,
2H), 7.16-7.10 (m, 2H), 6.26 (d, J ) 8.4 Hz, 2H), 5.34 (s, 1H),
2.60 (s, 3H), 2.10 (br s, 2H), 1.85-1.48 (m, 7H), 1.35-1.05 (m,
1H); 13C NMR (DMSO-d6) δ 145.2, 132.7, 127.9, 124.3, 119.6,
111.9, 88.2, 78.3, 32.1, 24.9, 23.6, 21.2. Anal. Calcd for
(()-3-(1,2,3-Be n zot r ia zol-1-yl)-3,4-d im e t h yl-2-p e n -
ta n on e (8f). To a solution of 2,2-di(1,2,3-benzotriazol-1-yl)-
3,4-dimethyl-3-pentanole 7f (0.4 g, 1.14 mmol) in 1,2-dichlo-
rethane (20 mL) under nitrogen was added zinc bromide (1.3
g, 5.8 mmol), and the reaction mixture was refluxed for 4 h.
The reaction mixture was poured into the 1 N aqueous
hydrochloric acid and extracted by chloroform. The chloroform
solution was washed with water, dried over potassium carbon-
ate and evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel to give 8f as
an oil (20%): 1H NMR (CDCl3) δ 8.12 (d, J ) 7.1 Hz, 1H), 7.46-
7.35 (m, 3H), 3.28 (q, J ) 6.7 Hz, 1H), 1.98 (s, 3H), 1.86 (s,
3H), 1.09 (d, J ) 7.7 Hz, 3H), 0.82 (d, J ) 7.7 Hz, 3H); 13C
NMR (CDCl3) δ 204.9, 146.7, 132.3, 127.6, 124.1, 120.3, 111.0,
75.4, 31.3, 24.4, 18.0, 17.3, 15.8. Anal. Calcd for C13H17N3O:
C, 67.51; H, 7.41; N, 18.17. Found: C, 67.87; H, 7.85; N, 18.33.
1-[1-(1-Cycloh exen -1-yl)vin yl]-1,2,3-ben zotr ia zole (9).
To a solution of 1-[1,1-di(1,2,3-benzotriazol-1-yl)ethyl]cyclo-
hexanole 7e (0.3 g, 0.83 mmol) in 1,1,2,2-tetrachloroethane (20
mL) under nitrogen was added zinc bromide (0.95 g, 4.2 mmol)
and the reaction mixture was refluxed for 5 min. The reaction
mixture was poured into the 1 N aqueous hydrochloric acid
and extracted by chloroform. The chloroform solution was
washed with water, dried over potassium carbonate, and
evaporated under reduced pressure. The residue was purified
by column chromatography on silica gel to give 9 as an oil
(35%): 1H NMR (CDCl3) δ 8.08 (dd, J ) 8.2, 0.8 Hz, 1H), 7.49-
7.47 (m, 2H), 7.41-7.35 (m, 1H), 5.57 (s, 1H), 5.46 (t, J ) 4.1
Hz, 1H), 5.35 (s, 1H), 2.35-2.30 (m, 2H), 2.12-2.03 (m, 2H),
1.81-1.73 (m, 2H), 1.67-1.59 (m, 2H); 13C NMR (CDCl3) δ
145.4, 143.7, 133.6, 131.9, 129.9, 127.7, 123.9, 119.8, 110.6,
110.2, 25.5, 25.4, 22.2, 21.6. Anal. Calcd for C14H15N3: C, 74.64;
H, 6.71; N, 18.65. Found: C, 74.60; H, 7.01; N, 18.53.
(()-1-(1,2,3-Ben zot r ia zol-1-yl)p r op yl Met h yl Su lfid e
(10a ). The solution of 1-(1,2,3-benzotriazol-1-yl)methyl methyl
sulfide (2 g, 11.20 mmol) in THF (60 mL) was cooled to -78
°C, and the solution of n-BuLi (12.3 mmol, 1.58 M in hexane,
7.9 mL) was added dropwise. The reaction mixture was stirred
at the same temperature for 1 h, and the solution of ethyl
iodide (1.92 g, 12.3 mmol) in THF (15 mL) was added. The
mixture was stirred for an additional 1 h at -78 °C. Then
water was added (30 mL), and the product was extracted with
ether. The residue was purified by gradient column chroma-
tography using the mixture of hexanes/EtOAc (9:1-3:1) to give
10a as an oil (82%): 1H NMR (CDCl3) δ 8.09 (d, J ) 8.2 Hz,
1H), 7.83 (d, J ) 8.4 Hz, 1H), 7.52-7.46 (m, 1H), 7.44-7.36
(m, 1H), 5.85 (dd, J ) 8.8, 6.6 Hz, 1H), 2.50-2.26 (m, 2H),
1.89 (s, 3H), 0.94 (t, J ) 7.4 Hz, 3H); 13C NMR (CDCl3) δ 147.0,
131.1, 127.1, 124.1, 120.2, 111.3, 67.6, 27.6, 13.7, 11.3. Anal.
Calcd for C19H22N6O: C, 57.94; H, 6.32; N, 20.27. Found: C,
57.97; H, 6.36; N, 20.65.
Gen er a l P r oced u r e for th e P r ep a r a tion of In ter m ed i-
a tes (11b,c). The solution of 1-(1-methylthioethyl)-1,2,3-
benzotriazole 10 (1 g, 5.18 mmol) in THF (50 mL) was cooled
to -78 °C, and the solution of n-BuLi (5.70 mmol, 1.58 M in
hexane, 3.7 mL) was added dropwise. The reaction mixture
was stirred at the same temperature for 1 h, and the solution
of corresponding ketones (5.70 mmol) in THF (15 mL) was
added. The mixture was stirred for an additional 1 h at -78
°C. Then water was added (30 mL), and the product was
extracted with ether. The rescue was purified by crystalization
from ether to give 11b,c.
C
20H22N6O: C, 66.28; H, 6.12; N, 23.19. Found: C, 66.22; H,
6.58; N, 23.32.
(()-2,2-Di(1,2,3-ben zotr ia zol-1-yl)-3,4-d im eth yl-3-p en -
ta n ol (7f): microcrystals from methanol (80%); mp 170-172
°C; 1H NMR (DMSO-d6) δ 8.06 (dd, J ) 8.2, 2.9 Hz, 2H), 7.29-
7.22 (m, 2H), 7.17-7.09 (m, 2H), 6.45 (d, J ) 8.5 Hz, 1H), 6.24
(d, J ) 8.1 Hz, 1H), 5.44 (s, 1H), 2.65 (s, 3H), 2.46-2.31 (m,
1H), 1.45 (s, 3H), 0.97 (d, J ) 6.4 Hz, 3H), 0.82 (d, J ) 6.7 Hz,
3H); 13C NMR (DMSO-d6) δ 145.3, 145.1, 132.7, 132.5, 127.9,
127.8, 124.3, 124.2, 119.5, 119.5, 112.1, 112.0, 89.0, 80.7, 33.9,
24.3, 20.4, 19.8, 18.7. Anal. Calcd for C19H22N6O: C, 65.12; H,
6.33; N, 23.98. Found: C, 65.00; H, 6.53; N, 24.29.
(()-3-(1,2,3-Ben zotr iazol-1-yl)-3-ph en yl-2-bu tan on e (8b).
To a solution of 3,3-di(1,2,3-benzotriazol-1-yl)-2-phenyl-2-bu-
tanole 7b (0.4 g, 1 mmol) in 1,1,2,2-tetrachloroethane (20 mL)
under nitrogen was added zinc bromide (1.2 g, 5.3 mmol), and
the reaction mixture was refluxed for 15 min. The reaction
mixture was poured into the 1 N aqueous hydrochloric acid
and extracted by chloroform. The chloroform solution was
washed with water, dried over potassium carbonate and
evaporated under reduced pressure. The residue was purified
by column chromatography on silica gel to give 8b as an oil
(40%): 1H NMR (CDCl3) δ 8.10 (d, J ) 8.2 Hz, 1H), 7.42-7.24
(m, 7H), 6.66 (d, J ) 8.2 Hz, 1H), 2.27 (s, 3H), 2.20 (s, 3H); 13
C
NMR (CDCl3) δ 202.1, 146.4, 137.0, 132.8, 129.0, 128.9, 127.3,
127.0, 123.9, 120.2, 112.0, 75.2, 26.4, 24.8. Anal. Calcd for
C
16H15N3O: C, 72.43; H, 5.70; N, 15.84. Found: C, 72.70; H,
5.77; N, 15.96.
(()-2-(1,2,3-B e n zo t r ia zo l-1-y l)-1,2-d ip h e n y l-1-p r o -
p a n on e (8c). To a solution of 2,2-di(1,2,3-benzotriazol-1-yl)-
1,1-diphenyl-1-propanole 7c (0.3 g, 0.67 mmol) in 1,2-dichlo-
rethane (20 mL) under nitrogen was added zinc bromide (1.2
g, 3.5 mmol), and the reaction mixture was refluxed for 30
min. The reaction mixture was poured into the 1 N aqueous
hydrochloric acid and extracted by chloroform. The chloroform
solution was washed with water, dried over potassium carbon-
ate and evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel to give 8c as
an oil (55%): 1H NMR (CDCl3) δ 8.06 (d, J ) 8.0 Hz, 1H), 7.56-
7.53 (m, 2H), 7.43-7.20 (m, 10H), 6.74 (d, J ) 8.2 Hz, 1H),
2.61 (s, 3H); 13C NMR (CDCl3) δ 196.5, 146.6, 138.4, 135.3,
133.5, 132.7, 129.4, 129.0, 128.8, 128.3, 127.9, 127.3, 123.8,
120.2, 111.9, 75.1, 27.6. Anal. Calcd for C21H17N3O: C, 77.04;
H, 5.23; N, 12.83. Found: C, 77.00; H, 5.27; N, 12.80.
(()-2-(1,2,3-B e n zo t r ia zo l-1-y l)-2-m e t h y lc y c lo h e x -
a n on e (8d ). To a solution of 1-[1,1-di(1,2,3-benzotriazol-1-yl)-
ethyl]cyclopentanole 7d (0.3 g, 0.86 mmol) in 1,1,2,2-tetra-
chloroethane (20 mL) under nitrogen was added zinc bromide
(1 g, 4.4 mmol) and the reaction mixture was refluxed for 15
min. The reaction mixture was poured into the 1 N aqueous
hydrochloric acid and extracted by chloroform. The chloroform
solution was washed with water, dried over potassium carbon-
ate, and evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel to give 8d as
an oil (35%): 1H NMR (CDCl3) δ 8.10 (d, J ) 8.0 Hz, 1H), 7.47-
7.30 (m, 3H), 3.52-3.34 (m, 1H), 2.57-2.49 (m, 1H), 2.36-
2.25 (m, 1H), 2.16-1.83 (m, 5H), 1.73 (s, 3H); 13C NMR (CDCl3)
δ 207.1, 146.6, 131.8, 127.5, 123.9, 120.2, 110.6, 70.0, 39.5, 39.1,
28.0, 23.0. 21.3. Anal. Calcd for C13H15N3O: C, 68.10; H, 6.59;
N, 18.33. Found: C, 67.85; H, 6.67; N, 18.50.
(()-3-(1,2,3-Ben zotr ia zol-1-yl)-3-(m eth ylth io)-2-p h en yl-
2-bu ta n ol (m ixtu r e of tw o d ia ster eoisom er s) (11b): mi-
crocrystals from acetone (81%); mp 116-117 °C; 1H NMR
(CDCl3) δ 8.35 (d, J ) 8.2 Hz, 1H), 8.30 (d, J ) 7.9 Hz, 1H),
7.98 (d, J ) 7.6 Hz, 1H), 7.93 (d, J ) 8.1 Hz, 1H), 7.50-7.20
(m, 10H), 7.20-7.00 (m, 2H), 6.97-6.85 (m, 2H), 2.98 (s, 1H),
2.88 (s, 1H), 2.27 (s, 3H), 2.26 (s, 3H), 1.92 (s, 3H), 1.72 (s,
3H), 1.66 (s, 3H), 1.53 (s, 3H); 13C NMR (CDCl3) δ 146.2, 146.1,
142.7, 141.8, 134.5, 134.1, 127.8, 127.7, 127.4, 127.2, 126.6,
126.5, 126.4, 126.4, 123.7, 123.5, 119.3, 119.2, 116.0, 115.9,
J . Org. Chem, Vol. 69, No. 2, 2004 307

Katritzky et al.
81.0, 80.8, 80.3, 80.2, 26.4, 25.8, 24.7, 24.5, 11.7, 11.5. Anal.
Calcd for C17H19N3OS: C, 65.15; H, 6.11; N, 13.41. Found: C,
64.49; H, 6.25; N, 12.83.
13b as an oil (30%): 1H NMR (CDCl3) δ 7.37 (d, J ) 7.5 Hz,
1H), 7.32-7.17 (m, 2H), 7.16-7.09 (m, 1H), 3.52-3.47 (m, 2H),
2.41 (s, 3H), 2.12 (t, J ) 2.0 Hz, 3H); 13C NMR (CDCl3) δ 146.3,
142.2, 136.0, 135.6, 126.5, 123.9, 122.9, 117.9, 40.7, 16.0, 11.1.
Anal. Calcd for C11H12S: C, 74.95; H, 6.86; N, 0. Found: C,
74.94; H, 6.60; N, 0.06.
2-(Meth ylth io)-3-p h en yl-1H-in d en e (13c). To a solution
of 2-(1,2,3-benzotriazol-1-yl)-2-(methylthio)-1,1-diphenyl-1-pro-
panole 11c (0.5 g, 1.33 mmol) in 1,2-dichlorethane (20 mL)
under nitrogen was added zinc bromide (0.9 g, 4 mmol), and
the reaction mixture was refluxed for 5 min. The solvent was
evaporated under reduced pressure, and residue was purified
by column chromatography on silica gel using hexanes to give
13c as plates (70%): mp 86-87 °C; 1H NMR (CDCl3) δ 7.52-
7.38 (m, 5H), 7.36-7.19 (m, 3H), 7.16-7.08 (m, 1H), 3.63 (s,
2H), 2.34 (s, 3H); 13C NMR (CDCl3) δ 145.4, 141.9, 138.6, 138.1,
134.5, 128.8, 128.3, 127.4, 126.5, 123.7, 123.1, 118.7, 41.0, 15.5.
Anal. Calcd for C16H14S: C, 80.63; H, 5.92; N, 0. Found: C,
80.94; H, 6.00; N, 0.
(()-2-(1,2,3-Ben zotr iazol-1-yl)-2-(m eth ylth io)-1,1-diph en -
yl-1-p r op a n ol (11c): microcrystals from acetone (98%); mp
139-140 °C; 1H NMR (CDCl3) δ 8.00-7.84 (m, 2H), 7.58-7.47
(m, 2H), 7.42-7.10 (m, 10H), 4.19 (s, 1H), 2.46 (s, 3H), 1.71
(s, 3H); 13C NMR (CDCl3) δ 146.1, 143.0, 142.9, 134.0, 129.0,
128.3, 127.7, 127.5, 127.4, 127.3, 126.6, 123.6, 119.5, 115.4,
85.2, 80.6, 25.3, 12.7. Anal. Calcd for C22H21N3OS: C, 70.37;
H, 5.64; N, 11.19. Found: C, 70.62; H, 5.82; N, 10.95.
(()-2-(1,2,3-Ben zotr iazol-1-yl)-2-(m eth ylth io)-1,1-diph en -
yl-1-bu t a n ol (11d ). The solution of 1-(1,2,3-benzotriazol-1-
yl)propyl methyl sulfide 10a (1 g, 4.83 mmol) in THF (50 mL)
was cooled to -78 °C, and the solution of n-BuLi (5.31 mmol,
1.58 M in hexane, 3.4 mL) was added dropwise. The reaction
mixture was stirred at the same temperature for 1 h, and the
solution of benzophenone (1 g, 5.31 mmol) in THF (15 mL)
was added. The mixture was stirred for an additional 2 h at
-78 °C. Then water was added (30 mL), and the product was
extracted with ether. The rescue was purified by crystalization
from acetone to give 11d as microcrystals (96%): mp 123-
(()-1-Meth yl-2-(m eth ylth io)-3-p h en yl-1H-in d en e (13d ).
To a solution of 2-(1,2,3-benzotriazol-1-yl)-2-(methylthio)-1,1-
diphenyl-1-butanole 11d (0.5 g, 1.29 mmol) in 1,2-dichlor-
ethane (20 mL) under nitrogen was added zinc bromide (0.87
g, 3.86 mmol), and the reaction mixture was refluxed for 5
min. The solvent was evaporated under reduced pressure, and
the residue was purified by column chromatography on silica
gel using hexanes to give 13d as plates (78%): mp 73-74 °C;
1H NMR (CDCl3) δ 7.52-7.30 (m, 6H), 7.28-7.12 (m, 3H), 3.69
1
124 °C; H NMR (CDCl3) δ 8.22 (d, J ) 8.40 Hz, 1H), 8.00-
7.92 (m, 1H), 7.60-7.50 (m, 2H), 7.50-7.41 (m, 2H), 7.40-
7.27 (m, 2H), 7.23-7.14 (m, 3H), 7.14-7.06 (m, 3H), 5.25 (s,
1H), 3.21-3.08 (m, 1H), 2.60-2.46 (m, 1H), 1.48 (s, 3H), 0.84
(t, J ) 7.2 Hz, 3H); 13C NMR (CDCl3) δ 145.4, 144.7, 142.3,
135.1, 129.5, 128.3, 127.5, 127.4, 127.1, 127.0 (2), 123.7, 119.9,
115.4, 86.2, 84.0, 29.4, 14.4, 9.5. Anal. Calcd for C23H23N3OS:
C, 70.92; H, 5.95; N, 10.79. Found: C, 70.76; H, 5.98; N, 10.81.
2-(Met h ylt h io)-1,1-d ip h en yl-2-p r op en -1-ol (12c). To a
solution of 2-(1,2,3-benzotriazol-1-yl)-2-(methylthio)-1,1-diphen-
yl-1-propanole 11c (0.2 g, 0.53 mmol) in 1,2-dichlorethane (10
mL) under nitrogen was added zinc bromide (0.36 g, 1.6 mmol),
and the reaction mixture was stirred at 25 °C for 15 min. The
solvent was evaporated under reduced pressure, and the
residue was purified by column chromatography on silica gel
using hexanes, to give 12c as an oil (89%): 1H NMR (CDCl3)
δ 7.42-7.36 (m, 4H), 7.35-7.27 (m, 6H), 5.12 (d, J ) 1.1 Hz,
1H), 4.98 (d, J ) 1.1 Hz, 1H), 3.29 (s, 1H), 2.29 (s, 3H); 13C
NMR (CDCl3) δ 153.9, 144.2, 127.8, 127.7, 127.5, 112.2, 82.7,
16.4. Anal. Calcd for C16H16OS: C, 74.96; H, 6.29; N, 0.
Found: C, 74.68; H, 6.30; N, 0.30.
(q, J ) 7.4 Hz, 1H), 2.24 (s, 3H), 1.46 (d, J ) 7.4 Hz, 3H); 13
C
NMR (CDCl3) δ 148.3, 144.0, 143.7, 140.0, 134.5, 129.2, 128.2,
127.5, 126.6, 124.6, 122.5, 119.4, 46.0, 17.6, 16.7. Anal. Calcd
for C17H16S: C, 80.90; H, 6.39; N, 0. Found: C, 80.65; H, 6.61;
N, 0.
(()-3-Hyd r oxy-3-p h en yl-2-bu ta n on e (14). To a solution
of 3-(1,2,3-benzotriazol-1-yl)-3-(methylthio)-2-phenyl-2-butanol
11b (0.3 g, 0.96 mmol) in THF (20 mL) under nitrogen was
added zinc bromide (0.65 g, 2.87 mmol), and the reaction
mixture was stirred for 3 h. The solvent was evaporated under
reduced pressure, and the residue was purified by gradient
column chromatography using the mixture of hexanes/EtOAc
(9:1-3:1) to give 14 as colorless liquid (75%): 1H NMR (CDCl3)
δ 7.45-7.27 (m, 5H), 4.59 (s, 1H), 2.07 (s, 3H), 1.76 (s, 3H);
13C NMR (CDCl3) δ 209.6, 141.3, 128.6, 127.9, 125.8, 79.8, 24.0,
23.4. The spectral data of this compound is identical to that
reported in the literature.17
2-(Meth ylth io)-3-m eth yl-1H-in d en e (13b). To a solution
of 3-(1,2,3-benzotriazol-1-yl)-3-(methylthio)-2-phenyl-2-butanol
11b (0.3 g, 1.60 mmol) in 1,2-dichlorethane (20 mL) under
nitrogen was added zinc bromide (0.65 g, 2.87 mmol), and the
reaction mixture was refluxed for 5 min. The solvent was
evaporated under reduced pressure and residue was purified
by column chromatography on silica gel using hexanes to give
Ack n ow led gm en t. We thank Dr. Xiaoming Zhao for
help in the initial phases of this work.
J O035098P
308 J . Org. Chem., Vol. 69, No. 2, 2004