One-carbon homologation of carboxylic acids via BtCH2TMS: A safe alternative to the Arndt-Eistert reaction

Article abstract of DOI:10.1021/jo0017640

Carboxylic acids are converted into the corresponding homologated acids or esters, using easily available 1-(trimethylsilylmethyl)benzotriazole (1) as a one-carbon synthon. The effectiveness of the reaction has been investigated on six aryl and seven alkyl carboxylic acids.

Full text of DOI:10.1021/jo0017640

5606
J . Org. Chem. 2001, 66, 5606-5612
On e-Ca r bon Hom ologa tion of Ca r boxylic Acid s via BtCH2TMS: A
Sa fe Alter n a tive to th e Ar n d t-Eister t Rea ction
Alan R. Katritzky,* Suoming Zhang,‡ Abdel Haleem Mostafa Hussein, and Yunfeng Fang
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Peter J . Steel
Department of Chemistry, University of Canterbury, Christchurch, New Zealand
katritzky@chem.ufl.edu
Received December 19, 2000
Carboxylic acids are converted into the corresponding homologated acids or esters, using easily
available 1-(trimethylsilylmethyl)benzotriazole (1) as a one-carbon synthon. The effectiveness of
the reaction has been investigated on six aryl and seven alkyl carboxylic acids.
In tr od u ction
or an acid derivative into a one-carbon higher homolo-
gated analogue: (1) The Arndt-Eistert reaction5 (Scheme
1a) is the most important and most commonly used
procedure for converting a carboxylic acid into its one-
carbon higher homologue acid (or ester or amide deriva-
tive) with diazomethane; however, to achieve high overall
yields, the intermediate diazo compounds often have to
be recrystallized, and freshly prepared silver benzoate
is required. The classical procedure also suffers from
handling difficulties, hindering the large-scale prepara-
tions: for example, R-diazomethyl ketones are hazardous
and strong skin irritant intermediates.5j Modified Arndt-
Eistert procedures ease these only in part.5i,k
(2) Barton’s radical homologation6 gives good yields but
employs the unstable intermediate O-acyl-N-hydroxy-
lthiopyridone and two-carbon radical trap, phenyl vinyl
sulfone, as a one-carbon synthon (Scheme 1b).
(3) Kowalski’s ester homologation with CH2Br2 syn-
thon7 affords good yields using the modified procedure.
A limitation is that a strong base is required (Scheme
1c).
Homologations of carbonyl compounds by a carbon-
carbon coupling reaction1 provide many attractive routes
to higher analogue carbonyl compounds with one,2 two,3
three,1 and four1,4 additional carbon atoms. These tech-
niques have enormously increased the synthetic utility
of the carbonyl-containing compounds and have greatly
diversified the nature of the chemical reactions available
to a synthetic chemist for the construction of new
carbon-carbon bonds. Since the synthetic exploitation
of carbonyl-containing and particularly acyl functional
groups plays a commanding role in the construction of a
molecular backbone, reaction sequences that result in a
carbon chain extension at a carbonyl group by one or
more carbon atoms producing an aldehyde, ketone, or
carboxylic acid are especially significant.
Among these reactions, one-carbon homologation of
carbonyl compounds is the most important. Three general
methods are available for the direct conversions of an acid
‡ Current address: Neurogen Corp., 35 Northeast Industrial Rd.,
Branford, CT 06405.
(1) For reviews: (a) Martin, S. F. Synthesis 1979, 633. (b) Stowell,
J . C. Chem. Rev. 1984, 84, 409.
In our preliminary communication,8 we have reported
that 1-(trimethylsilylmethyl)benzotriazole (1) reacts with
acyl chlorides to give the corresponding one-carbon
homologated acids or esters. In this paper, we describe
in detail our study of a convenient, safe alternative for
acid homologation with the one-carbon synthon 1-(trim-
ethylsilylmethyl)benzotriazole (1), utilizing the anion-
stabilizing and leaving-group properties of benzotriazole.9
(2) For one-carbon homologation: (a) Satoh, T.; Kubota, K. Tetra-
hedron Lett. 2000, 41, 2121. (b) Werner, R. M.; Shokek, O.; Davis, J .
T. J . Org. Chem. 1997, 62, 8243. (c) Maruoka, K.; Concepcion, A. B.;
Yamamoto, H. J . Org. Chem. 1994, 59, 4725. (d) Satoh, T.; Mizu, Y.;
Hayashi, Y.; Yamakawa, K. Tetrahedron Lett. 1994, 35, 133. (e)
Schummer, D.; Hofle, G. Tetrahedron 1995, 51, 11219. (f) Trost, B.
M.; Mikhail, G. K. J . Am. Chem. Soc. 1987, 109, 4124.
(3) For two-carbon homologation: (a) Barton, D. H. R.; Liu, W.
Tetrahedron Lett. 1997, 38, 2431. (b) Cabezas, J . A.; Oehlschlager, A.
C. Tetrahedron Lett. 1995, 36, 5127. (c) Bellassoued, M.; Lensen, N.;
Bakasse, M.; Mouelhi, S. J . Org. Chem. 1998, 63, 8785.
Resu lts a n d Discu ssion
(4) Bellassoued, M.; Salemkour, M. Tetrahedron Lett. 1993, 34, 5281.
(5) (a) Mulzer, J . In Comprehensive Organic Functional Group
Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon Press: Oxford, 1995; Vol. 5, pp 146 and 276. (b) Skeean, R.
W.; Goel, O. P. Synthesis 1990, 628. (c) Ancliff, R. A.; Russell, A. T.;
Sanderson, A. J . Tetrahedron: Asymmetry 1997, 8, 3379. (d) Podlech,
J .; Seebach, D. Liebigs Ann. 1995, 1217. (e) Podlech, J .; Seebach, D.
Angew. Chem., Int. Ed. Engl. 1995, 34, 471. (f) Marti, R. E.; Bleicher,
K. H.; Bair, K. W. Tetrahedron Lett. 1997, 38, 6145. (g) Limal, D.;
Quesnel, A.; Briand, J .-P. Tetrahedron Lett. 1998, 39, 4239. (h)
Guichard, G.; Abele, S.; Seebach, D. Helv. Chim. Acta 1998, 81, 187.
(i) Winum, J .-Y.; Kamal, M.; Leydet, A.; Roque, J .-P.; Montero, J .-L.
Tetrahedron Lett. 1996, 37, 1781. (j) Lee, V.; Newman, M. S. Org.
Synth. 1988, 613. (k) Aller, E.; Molina, P.; Lorenzo, A. Synlett 2000,
4, 526.
P r ep a r a tion of 1-(Tr im eth ylsilylm eth yl)ben zot-
r ia zole (1) a n d N-Acylm eth ylben zotr ia zoles 3a -m .
1-(Trimethylsilylmethyl)benzotriazole (1) and N-acylm-
(6) (a) Barton, D. H. R.; Chern, C.-Y.; J aszberenyi, J . S. Tetrahedron
Lett. 1992, 33, 5013. (b) Barton, D. H. R.; Chern, C.-Y.; J aszberenyi,
J . S. Tetrahedron Lett. 1991, 32, 3309.
(7) (a) Reddy, R. E.; Kowalski, C. J . Org. Synth. 1992, 146. (b)
Kowalski, C. J .; Haque, M. S.; Fields, K. W. J . Am. Chem. Soc. 1985,
107, 1429.
(8) Katritzky, A. R.; Zhang, S.; Fang, Y. Org. Lett. 2000, 2, 3789.
(9) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. V. Chem. Rev.
1998, 98, 409.
10.1021/jo0017640 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/18/2001

Homologation of Carboxylic Acids via BtCH2TMS
J . Org. Chem., Vol. 66, No. 16, 2001 5607
Sch em e 1
Sch em e 2a
a
Reagents and conditions: (i) THF, reflux; (ii) Tf2O, 2,6-lutidine,
CH2Cl2, 0-20 °C; (iii) (a) NaOCH3, acetonitrile, 65 °C, 2 h, (b)
concentrated HCl in an alcohol, reflux.
F igu r e 1. Perspective view of the X-ray crystal structure of
4a .
observed, indicating that the alkyl and Bt groups in 4j
are mutually trans. For aromatic compounds 4a -f, no
obvious NOE were observed resulting from the rotation
of the aryl group, which may be perpendicular to the
olefin.
Ta ble 1. On e-Ca r bon Hom ologa tion of Ca r boxylic Acid
Ch lor id es 2 to Der iva tives 7
isolated yields (%)
2
R
3
4
5
7a
To clarify the stereochemistry of these compounds, an
X-ray crystal structure determination was carried out on
4a . Figure 1 shows a perspective view of the structure,
which confirms unambiguously the Z-stereochemistry of
the enol triflate. In the solid state, the planes of the
phenyl and benzotriazole ring systems are inclined to the
plane of the double bond at angles of 25.3(3) and 36.4-
(3)°, respectively.
Con ver sion of Ar om a tic En ol Tr ifla tes 4a -f in to
th e Cor r esp on d in g Ester s. Treatment of aromatic enol
triflates 4a -f with 2.2 equiv of NaOCH3 in acetonitrile
at 65 °C for 2 h followed by hydrolysis with concentrated
HCl in methanol or ethanol afforded the methyl or ethyl
ester 7a -f in good to excellent yield depending on the
alcohol used (Table 1).
We postulate the reaction sequence outlined in Scheme
3. Enol triflate 4a was treated with 2 N NaOH in THF
at 20 °C for 30 min to afford 1-(2-phenylethynyl)-1H-
1,2,3-benzotriazole (5a ) (previously prepared in 56% yield
using phenylethynyl phenyliodonium tosylate11) in quan-
titative yield. The effects of the base and solvent are
small, using 2 N NaOH/THF or NaOCH3/CH3CN gave
similar results. Aromatic alkynylbenzotriazoles 5b-d ,11
e, and f were obtained using the same procedure in
excellent yields (Table 1).
a
C6H5
p-ClC6H4
p-CH3OC6H4
p-CH3C6H4
m-CH3C6H4
o-CH3C6H4
C6H5CH2CH2
CH3
(CH3)3CCH2
(CH3)3CCH2CH(CH3)CH2
CH3(CH2)4
85
90
90
91
87
90
94
83
95
90
97
95
86
95
95
93
90
83
87
96
88
95
98
94
90
82
98
97
92
95
91
92
94
90
98
96
92
92
89b
98c
93c
90c
92c
92c
24d
68d
62d
48d
59d
49d
b
c
d
e
f
g
h
i
j
k
l
n-CH3(CH2)6
p-ClC6H4CH2
m
Isolated yield. Methyl ester from 4 (Method A). c Ethyl ester
a
b
d
from 4 in one-pot reaction (method A). Acid from 8.
ethylbenzotriazoles 3a -m (Table 1) were prepared ac-
cording to the literature procedures in good yields (83-
97%).10
P r ep a r a tion of En ol Tr ifla tes 4a -m . Z-Enol tri-
flates 4a -m can be easily obtained stereoselectively from
N-acylmethylbenzotriazoles 3a -m (Scheme 2): treat-
ment of 3a -m with triflic anhydride (Tf2O) in the
presence of 2,6-lutidine at 0-20 °C for 2-12 h affords
the corresponding enol triflates 4 in excellent isolated
yields (82-98%) (see Table 1 and Scheme 2); no stereoi-
somers were isolated. The Z-configuration of the enol
triflate 4j was assigned on the basis of NOE experiments.
On irradiation of the vinylic proton in 4j at 7.42 ppm,
NOE between the methylene group and this proton was
Refluxing a reaction mixture of 5a and NaOCH3 in
acetonitrile at 65 °C for 2 h afforded 1-[(E)-1-methoxy-
(11) (a) Kitamura, T.; Tashi, N.; Tsuda, K.; Fujiwara, Y. Tetrahedron
Lett. 1998, 39, 3787. (b) Kitamura, T.; Tashi, N.; Tsuda, K.; Chen, H.;
Fujiwara, Y. Heterocycles 2000, 52, 303.
(10) Katritzky, A. R.; Lam, J . N. Heteroatom Chem. 1990, 1, 21.

5608 J . Org. Chem., Vol. 66, No. 16, 2001
Katritzky et al.
Sch em e 3a
was best carried out by the treatment of 8g-l with 1
equiv of TBAF in THF at 70 °C. Direct treatment of 5l
with p-toluenesulfonic acid followed by the hydrolysis
with TBAF in THF without the isolation of intermediate
8l also generated 7l in 49% GC yield (21% isolated yield).
This one-pot procedure, though more convenient, affords
a lower yield of the product. As shown in Table 2, various
conditions for the hydrolysis of 8l were investigated. The
reaction conditions gave only moderate GC yield (10-
34%).
Con clu sion
a
Reagents and conditions: (i) (a) NaOCH3 in CH3CN, 65 °C,
In summary, a concise and practical procedure for the
transformation of both aromatic and aliphatic carboxylic
acids into one-carbon homologated acid derivatives in
good to excellent yields has been developed using readily
available, versatile, and high-yielding reagent 1-(trim-
ethylsilylmethyl)benzotriazole (1) as a one-carbon syn-
thon. The mildness of the reaction conditions, good yields,
and the simple workup procedure show the usefulness
of this novel approach. 1-Alkynylbenzotriazoles 5a -l
greatly extends the scope of benzotriazole chemistry.
(b) concentrated HCl in an alcohol, 70 °C; (ii) NaOCH3 in CH3CN
or NaOH in THF, 20 °C; (iii) NaOCH3, acetonitrile, 65 °C, 2 h;
(iv) concentrated HCl in an alcohol, 70 °C.
2-phenylethenyl]-1H-1,2,3-benzotriazole (E-6a )12 as the
major product together with 1-[(Z)-1-methoxy-2-phe-
nylethenyl]-1H-1,2,3-benzotriazole (Z-6a )12 as the minor
product. No regioisomers were isolated. NOE experi-
ments with E-6a displayed the interaction between OCH3
group and the vinylic proton when the vinylic proton at
6.11 ppm was irradiated. The ratio of E/Z-6a is about
80:20 on the basis of 1H NMR spectra of the crude
product. Analogous intermediate E-6d can be isolated in
85% yield. The mixture of E-6a and Z-6a was hydrolyzed
with concentrated HCl in methanol under reflux yielding
the homologated methyl 2-phenylacetate 7a in 96% yield.
Ethyl 2-(4-chlorophenyl)acetate 7b was similarly ob-
tained by treatment of 5b with 1.0 equiv of NaOCH3 in
CH3CN under reflux followed by hydrolysis with concen-
trated HCl in ethanol in 98% overall yield. Analogous
two-step reactions from 4 gave 7c-f in excellent yields
(Table 1).
Con ver sion of Alip h a tic En ol Tr ifla tes 4g-l in to
th e Cor r esp on d in g Acid s. Applied to the aliphatic
series, the above procedure gives different results. Allene
compound 9i (34%) and compound 10i (27%) with the
triple bond shifted were obtained when 4i or 5i was
treated with NaOCH3 in CH3CN at 65 °C using the
discussed procedure above (Scheme 4). No desired ad-
ducts were formed. Similar treatment of 4j gave only
triple bond shifted compound 10j in 42% yield.
However, when aliphatic enol triflates 4g-m were
treated with 2.2 equiv of NaOCH3/CH3CN or 2 N NaOH/
THF at room temperature for 1 h, aliphatic alkynylben-
zotriazoles 5g-l were obtained in good yields after
workup (Table 1). Significantly, the only other known
attempt to prepare similar compounds, using direct
alkynylation of benzotriazole with alkynyliodonium salts,
failed.11 However, for 4m , only allene compound 9m was
isolated in 75% yield even at 20 °C, which is not
surprising because of the high acidity of benzylic and
allylic protons compared to a sp2 vinylic proton (Scheme
4).
Treatment of 5g-l with p-toluenesulfonic acid mono-
hydrate in acetonitrile at 65 °C for 2-12 h generated enol
toluenesulfonates 8g-l in good yields with a small
amount of the regioisomers (about 10%) and small
amount of hydrolyzed product 7g-l (5%). For compound
5g, the yield of 8g is poor because cyclization product
11g was isolated in 30% yield. The generation of 7g-l
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on a
MEL-TEMP capillary melting point apparatus equipped with
a Fluke 51 digital thermometer. NMR spectra were recorded
in CDCl3 with tetramethylsilane as the internal standard for
1H (300 MHz) and 13C (75 MHz). THF was distilled from
sodium/benzophenone under nitrogen immediately prior to
use. All reactions with air-sensitive compounds were carried
out under argon atmosphere. Column chromatography was
conducted with silica gel (230-400 mesh).
Typ ica l P r oced u r e for th e P r ep a r a tion of 4. To a cooled
(0 °C) solution of 3a -m (10 mmol) and 2,6-lutidine (3.47 mL,
20 mmol) in 20 mL of dry CH2Cl2 was added dropwise Tf2O
(3.36 mL, 14 mmol). After the mixture was stirred for 10 min,
the ice bath was removed, and the reaction mixture was
allowed to warm to 25 °C and stirred overnight. Hexane (20
mL) was added to the reaction mixture. The pyridinium salt
was filtered off, and the precipitate was washed with ethyl
acetate. The filtrate was washed with saturated NH4Cl, brine,
and H2O, dried over MgSO4, and concentrated in vacuo to
dryness. The residue was recrystallized from hexanes-ethyl
acetate to afford white crystals of 4a -m in yields of 82-98%.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-p h en yleth en yl tr i-
flu or om eth a n esu lfon a te (4a ): white needles; mp 98-99 °C
(95%, hexane-ethyl acetate); 1H NMR (300 MHz, CDCl3) δ
8.13 (1H, dd, J ) 8.3, 0.7 Hz, Bt), 7.70-7.75 (2H, m), 7.62-
7.63 (2H, m), 7.60 (1H, s, CHd), 7.45-7.55 (4H, m); 13C NMR
(75 MHz, CDCl3) δ 145.3 (s), 142.3 (s), 132.4 (s), 131.0 (d), 129.6
(s), 129.2 (d, 2 × CH), 128.8 (d), 126.2 (d, 2 × CH), 124.9 (d),
120.5 (d), 118.2 (q, J ) 319.0 Hz, CF3), 113.8 (d), 109.9 (d).
Anal. Calcd for C15H10F3N3O3S: C, 48.78; H, 2.73; N, 11.38.
Found: C, 48.89; H, 2.55; N, 11.33.
Cr ysta l d a ta for 4a : C15H10F3N3O3S, MW 369.32, triclinic,
space group P-1, a ) 6.258(3) Å, b ) 10.756(5) Å, c ) 12.458-
(6) Å, R ) 104.722(5)°, â ) 93.709(6)°, γ ) 96.542(6)°, V )
801.9(6) Å3, F(000) ) 376, Z ) 2, T ) -100 °C, µ(Mo KR) )
0.255 mm-1, Dcalcd ) 1.530 g‚cm-3, 2θmax 50° (CCD area
detector, Mo KR radiation), GOF ) 1.095, wR(F2) ) 0.1330
(all 2618 data), R ) 0.0514 (2145 data with I > 2σI).
(Z)-2-(1H -1,2,3-Ben zot r ia zol-1-yl)-1-(4-ch lor op h en yl)-
eth en yl tr iflu or om eth a n esu lfon a te (4b): white needles; mp
156-157 °C (95%, hexane-ethyl acetate); 1H NMR (300 MHz,
CDCl3) δ 8.14 (1H, d, J ) 8.3 Hz, Bt), 7.64-7.67 (5H, m), 7.51-
7.17 (3H, m); 13C NMR (75 MHz, CDCl3) δ 145.3 (s), 140.9 (s),
137.2 (s), 132.4 (s), 129.6 (s), 129.5 (d), 128.8 (d), 127.4 (d),
125.0 (d), 120.5 (d), 118.0 (q, J ) 319.0 Hz, CF3), 114 (d), 109.7
(12) Katritzky, A. R.; Zhao, X.; Shcherbakova, I. V. J . Chem. Soc.,
Perkin Trans. 1 1991, 3295.

Homologation of Carboxylic Acids via BtCH2TMS
J . Org. Chem., Vol. 66, No. 16, 2001 5609
Sch em e 4a
a
Reagents and conditions: (i) NaOCH3 in CH3CN or NaOH in THF, 20 °C; (ii) p-TSA in CH3CN, 65 °C, 2-12 h; (iii) TBAF in THF, 65
°C, 3-7 h; (iv) (a) p-TSA in CH3CN, reflux, (b) 2 N NaOH in acetone or TBAF in THF, reflux; (v) NaOCH3 in CH3CN, 65 °C.
Ta ble 2. Hyd r olysis of 8l to 7l u n d er Differ en t
Con d ition s
(Z)-2-(1H-1,2,3-Ben zotr iazol-1-yl)-4-ph en yl-1-bu ten yl tr i-
flu or om eth a n esu lfon a te (4g): white needles; mp 95-96 °C
1
(87%, hexane-ethyl acetate); H NMR δ 8.09 (1H, d, J ) 8.2
entry
reagent
solvent
time (h)
T (°C)
yielda (%)
Hz), 7.53 (1H, t, J ) 7.7 Hz), 7.42 (1H, t, J ) 7.8 Hz), 7.35
(1H, d, J ) 7.1 Hz), 7.24-7.30 (4H, m), 6.98 (1H, s), 3.10 (2H,
t, J ) 7.0 Hz), 3.00 (2H, t, J ) 7.0 Hz); 13C NMR δ 145.2 (s),
144.7 (s), 138.6 (s), 132.3 (s), 128.9 (d, 2 × CH), 128.5 (d, 3 ×
CH), 127.0 (d), 124.6 (d), 120.3 (d), 114.8 (d), 109.8 (d), missing
CF3, 34.5 (t), 32.5 (t). Anal. Calcd for C17H14F3N3O3S: C, 51.38;
H, 3.55; N, 10.57. Found: C, 51.50; H, 3.57; N, 10.87.
1
2
3
4
concd HCl
2 N NaOH
2 N NaOH
2 N NaOH
EtOH
24
4
2
70
20
20
75
25
34
28
10
DMSO
acetone
EtOH
a
GC results of crude product.
(d). Anal. Calcd for C15H9ClF3N3O3S: C, 44.62; H, 2.25; N,
10.14. Found: C, 44.49; H, 2.19; N, 10.22.
(Z)-2-(1H -1,2,3-Ben zot r ia zol-1-yl)-1-p r op en yl t r iflu o-
r om eth a n esu lfon a te (4h ): white microcrystals; mp 115-116
°C (88%, hexane-ethyl acetate); 1H NMR δ 8.11 (1H, dd, J )
8.21, 0.9 Hz, Bt), 7.49-7.62 (2H, m), 7.41-7.47 (1H, m), 7.13
(1H, q, J ) 1.2 Hz, CH )), 2.43 (3H, d, J ) 1.2 Hz, CH3); 13C
NMR δ 145.2 (s), 142.4 (s), 132.3 (s), 128.6 (d), 124.7 (d), 120.3
(d), 118.5 (q, J ) 319 Hz, CF3), 114.1 (d), 109.8 (d), 18.8 (q).
Anal. Calcd for C10H8F3N3O3S: C, 39.09; H, 2.62; N, 13.68.
Found: C, 39.49; H, 2.45; N, 13.59.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(4-m eth oxyp h en yl)-
eth en yl tr iflu or om eth a n esu lfon a te (4c): white needles; mp
113-114 °C (93%, hexane-ethyl acetate); 1H NMR (300 MHz,
CDCl3) δ 8.12 (1H, d, J ) 8.4 Hz), 7.66 (2H, d, J ) 8.9 Hz),
7.59-7.61 (2H, d, J ) 4.5 Hz), 7.49 (1H, s), 7.46 (1H, t, J )
4.6 Hz), 7.03 (2H, d, J ) 8.9 Hz), 3.38 (3H, s); 13C NMR (75
MHz, CDCl3) δ 161.8 (s), 145.2 (s), 143.0 (s), 132.5 (s), 128.6
(d), 127.9 (d, 2 × CH), 124.8 (d), 123.0 (s), 120.4 (d), 118.0 (q,
J ) 319.0 Hz, CF3), 114.6 (d, 2 × CH), 112.2 (d), 109.9 (d),
55.5 (q). Anal. Calcd for C16H12F3N3O4S: C, 48.12; H, 3.03; N,
10.52. Found: C, 48.12; H, 3.02; N, 10.38.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(4-m eth ylp h en yl)-
eth en yl tr iflu or om eth a n esu lfon a te (4d ): white needles; mp
147-148 °C (90%, hexane-ethyl acetate); 1H NMR δ 8.10 (1H,
dd, J ) 8.3, 1.0 Hz, Bt), 7.59-7.62 (4H, m, Bt and aromatic
proton), 7.56 (1H, s, CH d), 7.42-7.48 (1H, m, Bt), 7.31 (2H,
d, J ) 8.1 Hz), 2.42 (3H, s, CH3); 13C NMR δ 145.2 (s), 142.8
(s), 141.5 (s), 132.5 (s), 129.9 (d, 2 × CH), 128.7 (d), 128.0 (s),
126.1 (d, 2 × CH), 124.8 (d), 120.3 (d), 118.0 (q, J ) 319.6 Hz,
CF3), 113.0 (d), 109.9 (d), 21.4 (q). Anal. Calcd for
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-4,4-d im eth yl-1-p en te-
n yl tr iflu or om eth a n esu lfon a te (4i): white needles; mp 97-
99 °C (95%, hexanes-ethyl acetate); 1H NMR δ 8.10 (1H, d, J
) 8.3 Hz, Bt), 7.58 (1H, t, J ) 8.3 Hz, Bt), 7.51 (1H, d, J ) 8.2
Hz, Bt), 7.43 (1H, t, J ) 8.2 Hz, Bt), 7.20 (1H, s, CHd), 2.55
(2H, s), 1.15 (9H, s); 13C NMR δ 145.1 (s), 144.3 (s), 132.2 (s),
128.6 (d), 124.6 (d), 120.1 (d), 118.0 (q, J ) 319 Hz, CF3), 116.0
(d), 109.9 (d), 46.2 (t), 31.7 (s), 29.3 (q, 3 × CH3). Anal. Calcd
for C14H16F3N3O3S: C, 46.28; H, 4.44; N, 11.56. Found: C,
46.29; H, 4.14; N, 11.43.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-4,6,6-tr im eth yl-1-h ep -
ten tyl tr iflu or om eth a n esu lfon a te (4j): white needles; mp
62-63 °C (94%, hexanes-ethyl acetate); 1H NMR δ 8.27 (1H,
d, J ) 8.4 Hz), 7.75 (1H, t, J ) 7.6 Hz), 7.64 (1H, d, J ) 8.2
Hz), 7.60 (1H, t, J ) 7.5 Hz), 7.42 (1H, s), 2.84 (1H, dd, J )
15.1, 6.1 Hz), 2.58 (1H, dd, J ) 15.1, 8.6 Hz), 2.20-2.26 (1H,
m), 1.55 (1H, dd, J ) 14.0, 3.2 Hz), 1.42 (1H, dd, J ) 14.0, 6.8
Hz), 1.32 (3H, d, J ) 6.7 Hz), 1.14 (9H, s, 3 × CH3); 13C NMR
δ 145.3 (s), 145.1 (s), 132.4 (s), 128.6 (d), 124.6 (d), 120.4 (d),
114.9 (d), 109.9 (d), 50.4 (t), 42.3 (d), 31.0 (s), 29.9 (q, 3 × CH3),
27.0 (t), 22.0 (q). Anal. Calcd for C17H22F3N3O3S: C, 50.36; H,
5.47; N, 10.36. Found: C, 50.25; H, 5.56; N, 9.70.
C
16H12F3N3O3S: C, 50.13; H, 3.16; N, 10.96. Found: C, 50.19;
H, 2.97; N, 10.92.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(3-m eth ylp h en yl)-
eth en yl tr iflu or om eth a n esu lfon a te (4e): white microcrys-
tals; mp 122 °C (83%, hexane-ethyl acetate); 1H NMR δ 8.14
(1H, d, J ) 8.4 Hz), 7.62 (2H, d, J ) 3.8 Hz), 7.57 (1H, s),
7.54-7.35 (5H, m), 2.46 (3H, s); 13C NMR δ 145.3 (s), 142.8
(s), 139.2 (s), 132.5 (s), 131.9 (d), 131.0 (s), 129.2 (d), 128.7 (d),
126.8 (d), 124.9 (d), 123.5 (d), 120.6 (d), 113.6 (d), 109.9 (d),
21.4 (q), missing CF3.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(2-m eth ylp h en yl)-
eth en yl tr iflu or om eth a n esu lfon a te (4f): white needles; mp
102 °C (87%, hexane-ethyl acetate); H NMR δ 8.16 (1H, td,
J ) 8.2, 0.9 Hz), 7.63-7.57 (3H, m), 7.50-7.42 (2H, m), 7.35-
7.33 (3H, m), 2.58 (3H, s); 13C NMR δ 145.2 (s), 141.7 (s), 137.7
(s), 132.3 (s), 131.2 (d), 130.9 (d), 130.4 (d), 130.2 (s), 128.7
(d), 126.3 (d), 124.9 (d), 120.5 (d), 118.0 (q, J ) 319 Hz, CF3),
116.5 (d), 109.7 (d), 19.9 (q). Anal. Calcd for C16H12F3N3O3S:
C, 50.13; H, 3.16; N, 10.96. Found: C, 50.14; H, 3.04; N, 10.25.
(Z)-2-(1H -1,2,3-Ben zot r ia zol-1-yl)-1-h ep t en yl t r iflu o-
r om eth a n esu lfon a te (4k ): white needles; mp 84 °C (95%,
1
1
hexane-ethyl acetate); H NMR δ 8.10 (1H, d, J ) 8.2 Hz),
7.57 (1H, t, J ) 7.6 Hz), 7.50-7.40 (2H, m), 7.14 (1H, s), 2.67
(2H, t, J ) 7.4 Hz), 1.74-1.82 (2H, m), 1.49-1.38 (4H, m),
0.96 (3H, t, J ) 6.8 Hz); 13C NMR δ 146.4 (s), 145.3 (s), 132.4
(s), 128.5 (d), 124.6 (d), 120.3 (d), 117.9 (q, J ) 313.9 Hz, CF3),
113.8 (d), 109.9 (d), 32.7 (t), 30.8 (t), 26.0 (t), 22.2 (t), 13.8 (q).

5610 J . Org. Chem., Vol. 66, No. 16, 2001
Katritzky et al.
Anal. Calcd for C14H16F3N3O3S: C, 46.28; H, 4.44; N, 11.56.
Found: C, 46.44; H, 4.42; N, 11.51.
1-(4,6,6-Tr im e t h yl-1-h e p t yn yl)-1H -1,2,3-b e n zot r ia z-
ole (5j): oil (90%); H NMR δ 8.07 (1H, d, J ) 8.2 Hz), 7.64
1
(1H, d, J ) 8.2 Hz), 7.58 (1H, td, J ) 8.1, 0.6 Hz), 7.41 (1H,
td, J ) 8.1, 1.2 Hz), 2.57 (1H, dd, J ) 16.6, 5.76 Hz), 2.47 (1H,
dd, J ) 16.6, 6.8 Hz), 1.99-1.89 (1H, m), 1.47 (1H, dd, J )
14.0, 4.2 Hz), 1.22 (1H, dd, J ) 14.1, 6.2 Hz), 1.16 (3H, d, J )
6.6 Hz, CH3), 0.95 (9H, s, 3 × CH3); 13C NMR δ 143.6 (s), 134.2
(s), 128.8 (d), 124.8 (d), 120.1 (d), 109.8 (d), 79.5 (s), 68.4 (s),
49.9 (t), 30.8 (s), 29.7 (q, 3 × CH3), 28.9 (t), 28.0 (d), 22.0 (q).
Anal. Calcd for C16H21N3: C, 75.26; H, 8.29; N, 16.45. Found:
C, 75.25; H, 8.55; N, 16.82.
(Z)-2-(1H -1,2,3-Ben zot r ia zol-1-yl)-1-n on en yl t r iflu o-
r om eth a n esu lfon a te (4l): white needles; mp 77-78 °C (90%,
1
hexanes-ethyl acetate); H NMR δ 8.11 (1H, d, J ) 8.3 Hz,
Bt), 7.57 (1H, d, J ) 8.3 Hz, Bt), 7.50 (1H, t, J ) 8.3 Hz, Bt),
7.43 (1H, t, J ) 8.2 Hz, Bt), 7.14 (1H, s, CHd), 2.67 (2H, t, J
) 7.1 Hz), 1.78 (2H, m, CH2), 1.33-1.48 (8H, m, 4 × CH2),
0.91 (3H, t, J ) 6.6 Hz, CH3); 13C NMR (75 MHz, CDCl3) δ
146.6 (s), 145.5 (s), 132.6 (s), 128.8 (d), 124.9 (d), 120.6 (d),
118.0 (q, J ) 319 Hz, CF3), 114.1 (d), 110.2 (d), 32.9 (t), 31.8
(t), 29.0 (t), 28.9 (t), 26.6 (t), 22.8 (t), 14.3 (q). Anal. Calcd for
1-(1-Hep tyn yl)-1H-1,2,3-ben zotr ia zole (5k ): oil (92%); 1H
NMR δ 8.00 (1H, d, J ) 8.4 Hz), 7.57 (1H, d, J ) 8.1 Hz), 7.52
(1H, t, J ) 6.7 Hz), 7.35 (1H, t, J ) 8.0 Hz), 2.53 (2H, t, J )
7.1 Hz), 1.69-1.59 (2H, m), 1.48-1.28 (4H, m), 0.88 (3H, t, J
) 7.1 Hz); 13C NMR δ 143.4 (s), 134.1 (s), 128.8 (d), 124.7 (d),
120.0 (d), 109.8 (d), 80.3 (s), 67.6 (s), 30.8 (t), 27.8 (t), 21.9 (t),
18.3 (t), 13.7 (q). Anal. Calcd for C13H15N3: C, 73.21; H, 7.09;
N, 19.70. Found: C, 72.82; H, 7.13; N, 19.98.
C
15H10F3N3O3S: C, 49.10; H, 5.15; N, 10.74. Found: C, 48.98;
H, 5.17; N, 10.17.
(Z)-2-(1H-1,2,3-Ben zotr ia zol-1-yl)-3-(4-ch lor op h en yl)-1-
p r op en yl tr iflu or om eth a n esu lfon a te (4m ): white needles,
mp 115-116 °C (82%, hexanes-ethyl acetate); 1H NMR δ 8.07
(1H, dd, J ) 8.3, 1.0 Hz, Bt), 7.52 (1H, t, J ) 8.3 Hz, Bt), 7.51
(1H, d, J ) 8.3 Hz), 7.43 (1H, t, J ) 8.3 Hz, Bt), 7.05 (1H, s,
CHd), 3.93 (3H, s); 13C NMR δ 145.2 (s), 144.2 (s), 134.0 (s),
132.2 (s), 131.9 (s), 130.5 (d), 129.4 (d), 128.7 (d), 124.8 (d),
120.3 (d), 118.1 (q, CF3), 115.6 (d), 109.8 (d), 38.3 (t). Anal.
Calcd for C16H11ClF3N3O3S: C, 46.00; H, 2.65; N, 10.06.
Found: C, 46.14; H, 2.47; N, 10.00.
Typ ica l P r oced u r e for th e P r ep a r a tion of 5a -l. To a
solution of 4a -l (5 mmol) in 10 mL of THF was added 5 mL
of 10% NaOH at room temperature. After being stirred for 30
min, the reaction mixture was diluted with Et2O (60 mL),
washed with brine and H2O, dried over MgSO4, and concen-
trated in vacuo to dryness. The residue was purified by column
chromatography on silica gel using hexanes-ethyl acetate (10:
1) to afford 5a -l in the yields of 90-98%.
1
1-(1-Non yn yl)-1H-1,2,3-ben zotr ia zole (5l): oil; H NMR
(300 MHz, CDCl3) δ 8.07 (1H, d, J ) 8.3 Hz, Bt), 7.64 (1H, d,
J ) 8.3 Hz, Bt), 7.58 (1H, t, J ) 8.3 Hz, Bt), 7.45 (1H, t, J )
8.3 Hz, Bt), 2.59 (2H, t, J ) 7.1 Hz, CH2), 1.70 (2H, m, CH2),
1.50 (2H, m, CH2), 1.13 (6H, m), 0.89 (3H, t, J ) 6.6 Hz, CH3);
13C NMR (75 MHz, CDCl3) δ 143.6 (s), 134.3 (s), 128.9 (d), 124.9
(d), 120.2 (d), 109.9 (d), 80.5 (s), 67.8 (s), 31.6 (t), 28.8 (t), 28.7
(t), 28.2 (t), 22.5 (t), 18.5 (t), 14.0 (q). Anal. Calcd for
C
15H19N3: C, 74.65; H, 7.94; N, 17.41. Found: C, 74.42; H,
8.19; N, 17.66.
Typ ica l P r oced u r e for th e P r ep a r a tion of 6a ,12 6d .
Meth od A. To a solution of 4a or 4d (1 mmol) in acetonitrile
was added solid NaOCH3 (2 mmol) at room temperature. The
reaction mixture was heated under reflux for 2 h and then
cooled to room temperature. The reaction mixture was diluted
with Et2O, washed with brine and H2O, dried over MgSO4,
and evaporated in vacuo to dryness. Purification by flash
column chromatography on silica gel using hexane-ethyl
acetate (10:1) gave Z-6a and E-6a (or 6d ) as a colorless oil in
good yields (>80%).
1-[2-(3-Me t h ylp h e n yl)e t h yn yl]-1H -1,2,3-b e n zot r ia z-
ole (5e): white microcrystals; mp 80-81 °C (91%, hexane-
1
ethyl acetate); H NMR δ 8.13 (1H, d, J ) 8.2 Hz), 7.77 (1H,
d, J ) 8.2 Hz), 7.64 (1H, t, J ) 7.1 Hz), 7.50-7.43 (3H, m),
7.31 (1H, t, J ) 8.0 Hz), 7.26 (1H, d, J ) 7.0 Hz), 2.40 (3H, s);
13C NMR δ 143.9 (s), 138.4 (s), 134.3 (s), 132.4 (d), 130.4 (d),
129.3 (d), 128.9 (d), 128.5 (d), 125.2 (d), 120.6 (d), 120.0 (s),
110.2 (d), 80.0 (s), 75.5 (s), 21.2 (q). Anal. Calcd for C15H11N3:
C, 77.23; H, 4.75; N, 18.01. Found: C, 76.94; H, 4.71; N, 17.88.
1-[2-(2-Me t h ylp h e n yl)e t h yn yl]-1H -1,2,3-b e n zot r ia z-
ole (5f): white microcrystals; mp 79 °C (92%, hexane-ethyl
Meth od B. To a solution of 5a (219 mg, 1 mmol) in
acetonitrile was added solid NaOCH3 (1.1 mmol, 59.4 mg) at
room temperature. The reaction mixture was heated under
reflux for 2 h and then cooled to room temperature. The
reaction mixture was diluted with Et2O, washed with brine
and H2O, dried over MgSO4, and evaporated in vacuo to
dryness. The residue was purified by column chromatography
on silica gel using hexane-ethyl acetate (10:1) to give Z-6a
and E-6a as a colorless oil (total yield 98%).
1-[(Z)-1-Meth oxy-2-p h en yleth en yl]-1H-1,2,3-ben zotr ia -
zole (Z-6a ):12 colorless oil (18%); 1H NMR δ 8.14 (1H, dd, J )
1.0, 7.6 Hz), 7.78 (1H, dd, J ) 1.0, 7.6 Hz), 7.72 (2H, d, J )
7.3 Hz), 7.58 (1H, ddd, J ) 1.0, 7.6, 7.6 Hz), 7.39-7.47 (3H,
m), 7.30 (1H, ddd, J ) 1.0, 7.6, 7.6 Hz), 6.29 (1H, s), 3.65 (3H,
s). 13C NMR (75 MHz, CDCl3): δ 146.0 (s), 144.7 (s), 133.5 (s),
132.6 (s), 129.0 (d, 3 × CH), 128.9 (d, 2 × CH), 128.0 (d), 124.9
(d), 120.5 (d), 111.4 (d), 108.3 (d), 58.2 (q).
1-[(E)-1-Meth oxy-2-p h en yleth en yl]-1H-1,2,3-ben zotr ia -
zole (E-6a ).12 colorless oil (78%); 1H NMR δ 8.07 (1H, dd, J )
1.6, 8.6 Hz), 7.33-7.38 (2H, m), 7.20-7.26 (1H, m), 6.99-7.03
(3H, m), 6.62-6.68 (2H, m), 6.11 (1H, s), 3.98 (3H, s). 13C NMR
(75 MHz, CDCl3): δ 145.4 (s), 145.1 (s), 132.7 (s), 132.2 (s),
128.4 (d, 2 × CH), 128.3 (d), 127.5 (d, 2 × CH), 126.8 (d), 124.3
(d), 120.0 (d), 110.4 (d), 101.1 (d), 56.9 (q).
1-[(E)-1-Meth oxy-2-(4-m eth ylp h en yl)eth en yl]-1H-1,2,3-
ben zotr ia zole (E-6d ): colorless oil (85%); 1H NMR δ 8.12 (1H,
dd, J ) 0.9, 8.3 Hz), 7.78 (1H, dd, J ) 1.0, 7.6 Hz), 7.62 (2H,
d, J ) 8.1 Hz), 7.57 (1H, ddd, J ) 0.9, 7.6, 7.8 Hz), 7.44 (1H,
ddd, J ) 0.9, 7.6, 8.4 Hz), 7.22 (2H, d, J ) 8.1 Hz), 6.27 (1H,
s), 3.64 (3H, s), 2.39 (3H, s). 13C NMR (75 MHz, CDCl3): δ
145.7 (s), 143.9 (s), 137.3 (s), 132.3 (s), 130.3 (s), 129.3 (d, 3 ×
CH), 128.6 (d, 3 × CH), 124.6 (d), 120.2 (d), 111.1 (d), 108.1
(d), 57.8 (q), 21.3 (q); HRMS(EI) [M + H]+ calcd for C16H15N3O
266.1293, found 266.1293.
1
acetate); H NMR δ 8.14 (1H, dd, J ) 8.4, 0.9 Hz), 7.74 (1H,
dd, J ) 8.2, 0.9 Hz), 7.65 (1H, t, J ) 7.0 Hz), 7.62 (1H, d, J )
8.2 Hz), 7.49 (1H, t, J ) 7.0 Hz), 7.36-7.23 (3H, m), 2.60 (3H,
s); 13C NMR δ 146.8 (s), 144.0 (s), 140.4 (s), 134.3 (s), 132.2
(d), 129.8 (d), 129.5 (d), 129.4 (d), 125.9 (d), 125.3 (d), 120.6
(d); 110.1 (d), 78.7 (s), 74.1 (s), 21.0 (q). Anal. Calcd for
C
15H11N3: C, 77.23; H, 4.75; N, 18.01. Found: C, 77.24; H,
4.76; N, 17.90.
1-(4-P h en yl-1-bu tyn yl)-1H-1,2,3-ben zotr iazole (5g): white
needles; mp 72 °C (94%, hexane-ethyl acetate); 1H NMR δ
8.08 (1H, d, J ) 8.2 Hz), 7.54 (1H, t, J ) 7.1 Hz), 7.49-7.34
(2H, m), 7.32-7.25 (5H, m), 3.03 (2H, t, J ) 6.8 Hz), 2.91 (2H,
t, J ) 6.8 Hz); 13C NMR δ 143.7 (s), 139.9 (s), 134.4 (s), 129.0
(d), 128.3 (d, 2 × CH), 128.1 (d, 2 × CH), 126.6 (d), 125.0 (d),
120.3 (d), 110.0 (d), 79.6 (s), 68.6 (s), 34.5 (t), 20.8 (t). Anal.
Calcd for C16H13N3: C, 77.71; H, 5.30; N, 16.99. Found: C,
77.57; H, 5.56; N, 16.68.
1-(1-P r op yn yl)-1H-1,2,3-ben zotr ia zole (5h ): solid (90%);
1H NMR δ 8.08 (1H, d, J ) 8.3 Hz, Bt), 7.65 (1H, d, J ) 8.3
Hz, Bt), 7.58 (1H, t, J ) 8.3 Hz, Bt), 7.42 (1H, t, J ) 8.3 Hz,
Bt), 2.23 (3H, s); 13C NMR δ 143.5 (s), 134.1 (s), 128.9 (d), 124.9
(d), 120.2 (d), 109.9 (d), 76.3 (s), 66.8 (s), 3.5 (q, CH3). Anal.
Calcd for C9H7N3: C, 68.77; H, 4.49. Found: C, 69.10; H, 4.86.
1-(4,4-Dim eth yl-1-pen tyn yl)-1H-1,2,3-ben zotr iazole (5i):
solid (95%); 1H NMR δ 8.08 (1H, d, J ) 8.3 Hz, Bt), 7.62 (1H,
d, J ) 8.3 Hz, Bt), 7.58 (1H, t, J ) 8.3 Hz, Bt), 7.42 (1H, t, J
) 8.3 Hz, Bt), 2.48 (2H, s, CH2), 1.13 (9H, s, 3 × CH3); 13C
NMR δ 143.6 (s), 134.3 (s), 128.9 (d), 124.9 (d), 120.2 (d), 109.9
(d), 78.9 (s), 69.2 (s), 33.5 (t), 31.4 (s), 29.0 (q). Anal. Calcd for
C
13H15N3: C, 73.21; H, 7.09; N, 19.70. Found: C, 73.09; H,
Typical P r ocedu r e for th e P r epar ation of 7a -f. Meth od
A fr om 4a -f. To a cooled (0 °C) solution of enol triflates 4a -f
6.97; N, 20.04.

Homologation of Carboxylic Acids via BtCH2TMS
J . Org. Chem., Vol. 66, No. 16, 2001 5611
(7 mmol) in CH3CN (100 mL) was added NaOCH3 (15 mmol).
The reaction mixture was stirred for 2 h and then heated under
reflux for additional 2 h. After the solvent was removed in
vacuo, 50 mL of methanol or ethanol and 1 mL of concentrated
HCl was added, and the reaction mixture was heated under
reflux for 1-2 h. Methanol or ethanol was removed, and the
crude product was dissolved in diethyl ether , washed with
saturated Na2CO3 and H2O, and dried over MgSO4. The crude
ester was purified by column chromatograph with hexane/ethyl
acetate mixture (20:1) to provide the corresponding esters in
good yields.
J ) 7.8 Hz), 6.03 (1H, t, J ) 7.4 Hz), 2.27 (3H, s), 1.91 (2H, d,
J ) 7.4 Hz), 0.84 (9H, s); 13C NMR δ 145.4 (s), 144.7 (s), 135.1
(s), 132.2 (s), 131.5 (s), 129.2 (d, 2 × CH), 128.5 (d), 127.7 (d,
2 × CH), 124.3 (d), 120.9 (d), 119.6 (d), 110.4 (d), 39.8, 31.0,
28.9 (q, 3 × CH3), 21.3 (q). Anal. Calcd for C20H23N3O3S: C,
62.32; H, 6.01; N, 10.90. Found: C, 62.68; H, 6.28; N, 11.05.
1-(1H-1,2,3-Ben zotr ia zol-1-yl)-4,6,6-tr im eth yl-1-h ep te-
n yl 4-m eth ylben zen esu lfon a te (8j): oil (77%); 1H NMR δ
7.93 (1H, d, J ) 7.4 Hz), 7.43-7.52 (4H, m), 7.32-7.38 (1H,
m), 6.98 (2H, d, J ) 8.1 Hz), 5.97 (1H, t, J ) 7.9 Hz), 2.27
(3H, s), 1.95-2.00 (1H, m), 1.79-1.90 (1H, m), 1.58-1.68 (1H,
m), 0.92-1.12 (2H, m), 0.86 (3H, d, J ) 6.6 Hz), 0.79 (9H, s);
13C NMR δ 145.5, 144.9, 135.1, 132.3, 131.6, 129.3, (2CH),
128.6, 127.8 (2CH), 124.34, 122.4, 119.8, 110.6, 50.2, 35.4, 30.9,
29.8 (3 × CH3), 29.3, 22.4, 21.5; HRMS(EI) [M + H]+ calcd for
C23H29N3O3S 428.2008, found 428.2008.
1-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-h ep ten yl 4-m eth ylben -
zen esu lfon a te (8k ): oil (82%); 1H NMR δ 7.94 (1H, d, J )
7.4 Hz), 7.46-7.51 (4H, m), 7.33-7.38 (1H, m), 7.01 (2H, d, J
) 8.1 Hz), 5.94 (1H, t, J ) 7.9 Hz), 2.28 (3H, s), 1.99 (2H, dt,
J ) 7.5, 7.6 Hz), 1.38-1.43 (2H, m), 1.17-1.20 (4H, m), 0.82
(3H, t, J ) 6.5 Hz); 13C NMR δ 145.4, 144.7, 134.4, 132.2, 131.3,
129.2, (2CH), 128.4, 127.7 (2CH), 124.3, 123.1, 119.6, 110.4,
30.8, 28.4, 26.0, 22.0, 21.3, 13.6; HRMS(EI) [M + H]+ calcd
for C20H23N3O3S 386.1538, found 386.1538.
1-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-n on en yl 4-m eth ylben -
zen esu lfon a te (8l): pale yellow oil (75%); 1H NMR (300 MHz,
CDCl3) δ 7.94 (1H, d, J ) 8.2 Hz), 7.4-7.53 (4H, m), 7.38 (1H,
m), 7.00 (2H, d, J ) 8.2 Hz), 5.94 (1H, t, J ) 8.0 Hz), 2.28
(3H, s), 1.99 (2H, dt, J ) 8.0, 7.7 Hz), 1.40 (2H, m), 1.16-1.22
(8H, m), 0.82 (3H, t, J ) 7.0 Hz); 13C NMR (75 MHz, CDCl3)
δ 145.5 (s), 144.7 (s), 134.5 (s), 132.2 (s), 131.4 (s), 129.2 (d),
129.2 (d), 128.5 (d), 127.7 (d), 127.7 (d), 124.3 (d), 123.1 (d),
119.6 (d), 110.4 (d), 31.4 (t), 28.6 (t), 28.6 (t), 28.5 (t), 26.1 (t),
22.3 (t), 21.3 (q), 13.8 (q).
Typ ica l P r oced u r e for t h e P r ep a r a t ion of 9i,m a n d
10i,j. Compounds 5i,j, or 4i,j,m (1 mmol) were treated with
2.0 equiv of NaOCH3 in CH3CN (10 mL) under reflux for 2 h.
The solvent was removed in vacuo. The residue was dissolved
in ethyl acetate and washed with brine and H2O. The organic
layer was dried over MgSO4. Concentration in vacuo and
purification by flash chromatography afforded 9i,j,m and 10i,j,
respectively, in good yields.
Meth od B fr om 5a -f. Alkynylbenzotriazoles 5a -f were
treated with 1.0 equiv of NaOCH3 in CH3CN under reflux for
1-2 h followed by hydrolysis with concentrated HCl. The
reaction mixture was worked up as in method A, affording
desired esters in excellent yields.
1
Eth yl 2-(4-m eth oxyp h en yl)a ceta te (7c):13 oil (93%); H
NMR δ 7.19 (2H, d, J ) 8.4 Hz), 6.84 (2H, d, J ) 8.4 Hz), 4.12
(2H, q, J ) 7.1 Hz, CH2), 3.77 (3H, s, OCH3), 3.54 (2H, s, CH2),
1.48 (3H, t, J ) 7.1 Hz, CH3); 13C NMR δ 171.8 (s, CO2), 158.5
(s), 130.1(d, 2 × CH), 126.1 (s), 113.8 (d, 2 × CH), 60.6 (t),
55.1 (q), 40.3 (t), 14.0 (q).
Typ ica l P r oced u r e for th e P r ep a r a tion of 7g-l. Enol
tosylates 8g-l (1 mmol) were treated with 1.0 equiv of TBAF
in THF (10 mL) under reflux for 3-48 h. The reaction mixtures
were diluted and washed with 1 N HCl, saturated NaCl, and
H2O. The organic layers were dried over MgSO4, and the
solvent was evaporated in vacuo. Crude products were purified
by flash chromatography to provide the desired acids in good
yields.
4,4,6-Tr im eth ylh ep ta n oic a cid (7j):14 oil (62%); 1H NMR
δ 2.38-2.32 (2H, m), 1.69-1.61 (1H, m), 1.59-1.43 (2H, m),
1.25-1.18 (1H, dd, J ) 3.3, 14.0 Hz), 1.15-1.10 (1H, dd, J )
5.8, 14.0 Hz), 0.93 (3H, d, J ) 6.4 Hz), 0.89 (9H, s, 3 × CH3),
missing CO2H; 13C NMR δ 180.5 (s), 50.8 (t), 33.9 (t), 32.0 (t),
31.0 (s), 29.9 (q), 28.8 (d), 22.2 (q).
Typ ica l P r oced u r e for th e P r ep a r a tion of 8g-l. To a
solution of 5g-l (1 mmol) in acetonitrile 10 (mL) was added
p-toluenesulfonic acid monohydrate (190 mg, 1 mmol) at room
temperature. The reaction mixture was stirred under reflux
for 4 h until TLC showed no presence of the starting material.
The resulting mixture was concentrated in vacuo to dryness,
and the residue was purified by column chromatography on
silica gel using hexanes-EtOAc (10:1) as an eluent to afford
8g-l (yields of 65-85% except for 24% of 8g).
1-(4,4-Dim eth yl-1,2-p en ta d ien yl)-1H-1,2,3-ben zotr ia z-
1
ole (9i): oil (94%); H NMR δ 8.07 (1H, d, J ) 8.2 Hz), 7.87
1-(1H-1,2,3-Ben zotr ia zol-1-yl)-4-p h en yl-1-bu ten yl 4-m e-
(1H, d, J ) 6.2 Hz), 7.80 (1H, d, J ) 8.3 Hz), 7.48 (1H, dt, J )
1.0, 8.1 Hz), 7.42 (1H, dt, J ) 1.0, 8.1 Hz), 6.16 (1H, d, J ) 6.2
Hz), 1.20 (9H, s); 13C NMR δ 192.7 9s), 146.5 (s), 131.3 (s),
127.6 (d), 124.3 (d), 120.0 (d), 116.1 (d), 111.1 (d), 99.1 (d), 33.5
(s), 29.3 (q). Anal. Calcd for C13H15N3: C, 73.21; H, 7.09; N,
19.70. Found: C, 72.82; H, 7.14; N, 19.98.
1
th ylben zen esu lfon a te (8g): oil (24%); H NMR δ 7.91 (1H,
d, J ) 8.8 Hz), 7.43-7.41 (3H, m), 7.34-7.29 (2H, m), 7.20-
7.12 (3H, m), 7.02 (2H, d, J ) 6.8 Hz), 5.96 (2H, d, J ) 8.3
Hz), 5.93 (1H, t, J ) 7.6 Hz), 2.73 (2H, t, J ) 7.5 Hz), 2.34
(2H, dt, J ) 7.5, 7.6 Hz), 2.25 (3H, s); 13C NMR δ 145.5, 144.8,
139.9, 135.1, 132.0, 131.3, 129.2 (2 × CH), 128.5, 128.3 (2 ×
CH), 128.2 (2 × CH), 127.7 (2 × CH), 126.1, 124.4, 121.7, 119.6,
110.6, 34.8, 28.0, 21.4; HRMS (EI) [M + H]+ calcd for
1-[3-(4-Ch lor op h en yl)-1,2-p r op a d ien yl]-1H-1,2,3-ben zo-
1
tr ia zole (9m ): oil (75%); H NMR δ 8.23 (1H, d, J ) 6.3 Hz),
8.10 (1H, d, J ) 8.3 Hz), 7.68 (1H, d, J ) 8.2 Hz), 7.44-7.35
(6H, m), 7.10 (1H, d, J ) 6.3 Hz); 13C NMR δ 197.3 (s), 146.6
(s), 134.9 (s), 131.4 (s), 130.8 (s), 129.3 (d, 2CH), 129.1 (d, 2CH),
128.3 (d), 124.7 (d), 120.3 (d), 110.9 (d), 106.0 (d), 101.1 (d);
HRMS(EI) [M + H]+ calcd for C15H10ClN3 268.0642, found
268.0642.
C
C
23H21N3O3S 420.1382, found 420.1382. Anal. Calcd for
23H21N3O3S: C, 65.85; H, 5.05; N, 10.02. Found: C, 64.87;
H, 4.87; N, 10.19.
1-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-p r op en yl 4-m eth ylben -
zen esu lfon a te (8h ): white needles; mp 78-80 °C (62%,
1
hexanes-ethyl acetate); H NMR δ 7.94 (1H, d, J ) 8.2 Hz),
1-(4,4-Dim eth yl-2-pen tyn yl)-1H-1,2,3-ben zotr iazole (10i):
oil (94%); 1H NMR δ 8.05 (1H, d, J ) 8.3 Hz), 7.75 (1H, d, J )
8.3 Hz), 7.53 (1H, dt, J ) 0.9, 8.3 Hz), 7.51 (1H, dt, J ) 0.9,
8.3 Hz), 5.42 (2H, s), 1.20 (9H, s); 13C NMR δ 146.29s), 132.4
(s), 127.2 (d), 123.9 (d), 119.9 (d), 110.1 (d), 95.3 (s), 70.1 (s),
38.7 (t), 32.3 (s), 30.5 (q). Anal. Calcd for C13H15N3: C, 73.21;
H, 7.09; N, 19.70. Found: C, 72.82; H, 7.14; N, 19.98.
1-(4,6,6-Tr im e t h yl-2-h e p t yn yl)-1H -1,2,3-b e n zot r ia z-
ole (10j): white microcrystals; mp 75 °C (94%, hexane); 1H
NMR δ 8.04 (1H, d, J ) 8.4 Hz); 7.71 (1H, d, J ) 8.4 Hz), 7.49
(1H, t, J ) 7.3 Hz), 7.73 (1H, t, J ) 7.3 Hz), 5.50 (2H, s), 2.44-
2.50 (1H, m), 1.47 (1H, dd, J ) 9.7, 13.5 Hz), 1.19 (1H, dd, J
) 3.3, 13.3 Hz), 1.14 (3H, d, J ) 7.0 Hz), 0.86 (9H, s); 13C NMR
δ 146.1 (s), 132.4 (s), 127.1 (d), 123.8 (d), 119.8 (d), 110.0 (d),
93.2 (s), 71.7 (s), 50.4 (t), 38.6 (q), 30.7 (s), 29.5 (q), 23.2 (t),
7.50-7.44 (2H, m), 7.43 (2H, d, J ) 8.2 Hz), 7.33-7.39 (1H,
m), 6.98 (2H, d, J ) 8.2 Hz), 6.03 (1H, q, J ) 7.3 Hz), 2.27
(3H, s), 1.69 (3H, d, J ) 7.3 Hz); 13C NMR δ 145.5 (s), 144.9
(s), 135.3 (s), 132.3 (s), 131.6 (s), 129.3 (d, 2 × CH), 128.6 (d),
127.8 (d, 2 × CH), 124.4 (d), 119.8 (d), 117.9 (d), 110.6 (d),
21.5 (q), 11.9 (q). Anal. Calcd for C16H15N3O3S: C, 58.34; H,
4.59; N, 12.76. Found: C, 58.44; H, 4.72; N, 12.68.
1-(1H -1,2,3-Ben zot r ia zol-1-yl)-4,4-d im et h yl-1-p en t e-
n yl 4-m eth ylben zen esu lfon a te (8i): microcrystals; mp 56-
59 °C (67%, hexanes-ethyl acetate); 1H NMR δ 7.94 (1H, d, J
) 8.3 Hz), 7.51-7.45 (4H, m), 7.38-7.33 (1H, m), 7.00 (2H, d,
(13) Lu, X.; Silverman, R. B. J . Am. Chem. Soc. 1998, 120, 10583.
(14) Holmquist, H. E.; Carnahan, J . E. J . Org. Chem. 1960, 25, 2240.

5612 J . Org. Chem., Vol. 66, No. 16, 2001
Katritzky et al.
21.9 (d). Anal. Calcd for C16H21N3: C, 75.25; H, 8.29; N, 16.45.
Found: C, 75.21; H, 8.55; N, 16.83.
27.2 (t), 22.8 (t). Anal. Calcd for C16H13N3: C, 77.71; H, 5.30;
N, 16.99. Found: C, 77.90; H, 5.63; N, 17.16.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization for compounds 3a -l and 5a -d ,
7b,d -f,i; NMR spectra data for 4c,e-g,i-k ,m , 5e-k , 6c, 8g-
j, 9i,m , 10i,j, and 11g; and details of the X-ray crystal
structure of 4a . This material is available free of charge via
the Internet at http://pubs.acs.org.
1-(3,4-Dih yd r o-1-n a p h t h a len yl)-1H -1,2,3-b en zot r ia z-
ole (11g): solid (30%); 1H NMR δ 8.14 (1H, d, J ) 7.5 Hz),
7.45-7.35 (3H, m), 7.28?7.21 (2H, m), 7.07 (1H, dd, J ) 7.0,
7.8 Hz), 6.51 (1H, d, J ) 7.8 Hz), 6.44 (1H, t, J ) 4.8 Hz), 3.04
(2H, t, J ) 8.0 Hz), 2.67 (2H, m); 13C NMR δ 145.7 (s), 136.0
(s), 134.3 (s), 133.5 (s), 130.3 (s), 128.7 (d), 128.0 (d), 127.7 (d),
127.4 (d), 126.8 (d), 124.1 (d), 122.8 (d), 120.0 (d), 110.7 (d),
J O0017640