One-carbon homologation of aldehydes to N-(α-haloacyl)benzotriazoles

Article abstract of DOI:10.1055/s-2006-950183

One-carbon homologated N-(α-haloacyl)benzotriazoles have been synthesized from the corresponding aromatic and aliphatic aldehydes. Vinylbenzotriazoles, prepared by the reaction of aldehydes with the one-carbon synthon BtCH₂P⁺Ph₃

Full text of DOI:10.1055/s-2006-950183

PAPER
3231
One-Carbon Homologation of Aldehydes to N-(a-Haloacyl)benzotriazoles
O
ne-Carbon Hom
o
l
logatio
a
n of
A
lde
h
n
ydes to
N
-(
a
-Haloa
R
cyl)benzotriazol
.
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
Fax +1(352)3929199; E-mail: katritzky@chem.ufl.edu
Received 27 April 2006
Unlike acid chlorides, N-acylbenzotriazoles are stable,
crystalline compounds that can be stored at room temper-
ature without decomposition. Use of N-acylbenzotriazoles
avoids racemization,2b,2d assures regiospecificity,1g–h and
Abstract: One-carbon homologated N-(a-haloacyl)benzotriazoles
have been synthesized from the corresponding aromatic and ali-
phatic aldehydes. Vinylbenzotriazoles, prepared by the reaction of
aldehydes with the one-carbon synthon BtCH2P+Ph3Cl–, were sub-
sequently treated with Br2/Et3N to give 1-bromovinylbenzotri- the resulting products are generally obtained in high
azoles. These were then treated with NBS/NIS in CH3CN–H2O to
furnish one-carbon homologated N-(a-haloacyl)benzotriazoles in
53–77% yields. We have also demonstrated the utility of these new
isolate, for example RCOCl, with R = 4-diethylamino-
reagents in organic synthesis.
yields. They are also the reagents of choice when the cor-
responding acid chlorides are unstable or difficult to
phenyl, 2-pyridyl, 2-indolyl or 2-pyrrolyl. We recently re-
ported a mild, one-pot procedure for efficient conversion
Key words: N-acylbenzotriazole, homologation, aldehyde, acyla-
tion, N-halosuccinimide
of carboxylic acids into the corresponding N-
acylbenzotriazoles7 which has several advantages over
previous methods.2a,8
N-Acylbenzotriazoles1a are important synthetic reagents
a-Haloacyl halides are important reagents from which a
whose numerous applications in organic synthesis in-
wide variety of compounds may be obtained by replacing
clude: (i) C-acylation reagents for the synthesis of 1,3-,1b
both the halogens on the a-carbon and on the acyl func-
tion.9 Following the widespread utility of N-acylbenzotri-
azoles in organic synthesis, we now introduce N-(a-
haloacyl)benzotriazoles as convenient alternatives to a-
haloacyl halides. Analogous to acyl halides, a-haloacyl
halides are unstable and difficult to handle, and their prep-
aration involves vigorous conditions and extended reac-
tion times.10–11 The present method for the synthesis of N-
(a-haloacyl)benzotriazoles from aldehydes involves one
carbon homologation using BtCH2P+Ph3Cl– (1).
and 1,2-diketones,1c–d enaminones,1e 1-substituted-2-azi-
nyl-1-ethanones,1f and for the regiospecific acylation of
heterocycles;1g–h (ii) N-acylation reagents for the prepara-
tion of amides,2a–c peptides,2d and N-acylsulfonamides;2e
(iii) O-acylation reagents in their additions to aldehydes to
give esters;3 (iv) in the preparation of benzoxazoles by
flash vacuum pyrolysis;4 (v) in the syntheses of oxazo-
lines and thiazolines under microwave irradiation5 and
(vi) as S-acylation reagents in the synthesis of thiol esters6
(Scheme 1).
Reaction of 1 with n-BuLi and aryl, alkyl or heterocyclic
aldehydes (RCHO; R = Ph, p-tolyl, 2-thienyl etc.) gave
vinylbenzotriazoles 2a–j in 38–65% yields, following a
previously reported general procedure (Scheme 2,
Table 1).12 Treatment of 2a–j with bromine followed by
Et3N gave the corresponding 1-(1-bromovinyl)benzotria-
zoles 3a–j in 42–80% yields (Scheme 2, Table 1). The
vinylbenzotriazoles 2a–j and 1-(1-bromovinyl)benzotria-
R4
N
R4
O
R5
HN
O
O
R
NHR1
R5
R
R
R
O
N
H
R1NH2
(ii)
(iii)
R2
Bt
R2CHO
(iv)
N
O
1
zoles 3a–j were characterized by H and 13C NMR spec-
(i)
H
O
troscopy and elemental analysis.
R
Bt
C-acylation
SmI2
O
R
F.V.P.
(v)
O
R
O
N
Bt
(vi)
R1SH
Bt
O
Br2, r.t., 4 h
MW
R
n-BuLi, RCHO
Et3N, r.t., 14 h
BtCH2PPh3Cl
Br
R
R
DMSO, r.t., 14 h
2a–j, 38–65%
X
O
R3
–
N
O
O
CH2
R3
1
R
3a–j, 42–80%
SR1
R
R
X = O, S
O
NXS, HX (cat.)
Scheme 1
R
Bt
MeCN–H2O, r.t., 12 h
X = Br, I
X
4a–m, 53–77%
SYNTHESIS 2006, No. 19, pp 3231–3237
x
x.
x
x
.
2
0
0
6
Advanced online publication: 15.08.2006
DOI: 10.1055/s-2006-950183; Art ID: M02706SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 2 Synthesis of N-(a-haloacyl)benzotriazoles. For R, see
Table 1.

3232
A. R. Katritzky et al.
PAPER
Table 1 Preparation of 2-Substituted Vinylbenzotriazoles 2a–j, 1-Bromovinylbenzotriazoles 3a–j and N-(a-Haloacyl)benzotriazoles 4a–m
Entry
R
Yield (%)a
Yield (%)a
Yield (%)a
X = Br
X = I
1
Ph
2a (64)
2b (65)
2c (47)
2d (54)
2e (64)
2f (53)
2g (59)
2h (38)
2i (41)
2j (53)
3a (80)
3b (61)
3c (63)
3d (52)
3e (49)
3f (52)
3g (53)
3h (54)
3i (42)
3j (52)
4a (75)
4b (73)
4c (71)
4d (67)
4e (53)
4f (70)
4g (58)
4h (61)
4i (77)
–
–
2
p-Me C6H4
o-Me C6H4
Et
–
3
–
4
–
5
i-Pr
–
6
(CH3)2CHCH2
n-Pr
–
7
4k (69)
4l (53)
4m (64)
–
8
n-Heptyl
C6H5CH2CH2
Thienyl
9
10
a Isolated product yield.
Reaction of 1-(1-bromovinyl)benzotriazoles 3a–i with N-
bromosuccinimide (NBS) in the presence of a catalytic
amount of HBr in a mixture of acetonitrile and water, fur-
nished N-(a-bromoacyl)benzotriazoles 4a–i in 53–77%
yields (Scheme 2, Table 1). However, compound 3j,
which was prepared from a heterocyclic aldehyde (2-
thiophenecarboxaldehyde), did not give the correspond-
ing N-(a-bromoacyl)benzotriazole. Reaction of 3g–i with
N-iodosuccinimide (NIS) in the presence of a catalytic
amount of HI furnished N-(a-iodoacyl)benzotriazoles 4k–
m in good yields (Scheme 2, Table 1). N-(a-Halo-
acyl)benzotriazoles 4a–i and 4k–m are novel compounds
Table 2 Preparation of N-(a-Halo)amides and Ester 5a–h
Entry
4
Nucleophile
Yield (%)
5a (87)
5b (75)
5c (69)
5d (63)
5e (56)
5f (76)
5g (61)
5h (82)
1
2
3
4
5
6
7
8
4a
4f
4f
4f
4k
4l
C6H5CH2NH2
C6H5CH2NH2
C6H5(CH2)2NH2
p-Me-C6H4(CH2)2NH2
p-Me-C6H4(CH2)2NH2
p-Me-C6H4(CH2)2NH2
C6H5CH(CH3)NH2
C6H5CH2OH
1
and were fully characterized by H and 13C NMR spec-
4f
4k
troscopy and by elemental analysis.
In the applications of N-(a-haloacyl)benzotriazoles, treat-
ment of several N-(a-haloacyl)benzotriazoles with vari-
ous amines and alcohols gave N-(a-halo)amides and ester
5a–h in 56–87% yields (Scheme 3, Table 2). Compounds
5b and 5d–h are novel and were fully characterized by 1H
and 13C NMR spectroscopy and by elemental analysis.
Melting points are uncorrected. Solvents were dried according to
standard procedures. Aldehydes and benzotriazole were purchased
and used without further purification. Column chromatography was
carried out using silica gel 200–425 mesh. All of the reactions with
air-sensitive compounds were carried out under N2 atmosphere. 1H
NMR (300 MHz) and 13C NMR (75 MHz) spectra were recorded on
a Gemini 300 NMR spectrometer in CDCl3 (with TMS for 1H and
CDCl3 for 13C as the internal reference). Chemical shifts for minor
isomers are given in parenthesis.
O
O
nucleophile
R
R
Nu
Bt
Et3N, CH2Cl2, r.t., 2 h
X
X
4
5, 56–87%
Preparation of Vinylbenzotriazoles 2a–j; General Procedure
To a solution of [(benzotriazol-1-yl)methyl]triphenyl phosphonium
chloride (21.7 g, 50 mmol) in DMSO, n-BuLi (1.6 M, 31 mL, 50
mmol) was added under nitrogen at 25 °C. After 1 h, aldehyde (60
mmol) was added dropwise and the reaction was continued for 12
h. The reaction mixture was then poured into H2O (100 mL) and ex-
tracted with CHCl3 (2 × 150 mL). The organic layer was washed
with brine (2 × 50 mL) and dried over MgSO4. Evaporation of the
solvent gave a residue that was purified by column chromatography
(hexanes–EtOAc, 10:1) to give vinylbenzotriazoles 2a–j.
Scheme 3
In conclusion, we have developed a new methodology for
one-carbon homologation of both aliphatic and aromatic
aldehydes to N-(a-haloacyl)benzotriazoles using the one-
carbon synthon BtCH2P+Ph3Cl–. These N-(a-halo-
acyl)benzotriazoles are excellent acylating reagents.
Synthesis 2006, No. 19, 3231–3237 © Thieme Stuttgart · New York

PAPER
One-Carbon Homologation of Aldehydes to N-(a-Haloacyl)benzotriazoles
3233
1-[(E)-2-Phenyl-1-ethenyl]-1H-1,2,3-benzotriazole (2a)
Yield: 64%; white microcrystals; mp 112–114 °C (Lit.13 115–
116 °C).
1H NMR (300 MHz, CDCl3): d = 7.32–7.61 (m, 8 H), 7.77 (d,
J = 8.4 Hz, 1 H), 7.94 (dd, J = 12.9, 1.1 Hz, 1 H), 8.12 (d, J = 8.4
Hz, 1 H).
7.2 Hz, 1 H), 7.25–7.39 (m, 2 H), 7.46 (m, 1 H), 7.63 (d, J = 8.4 Hz,
1 H), 8.05 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.4, 22.2, 32.0, 109.9, 119.8,
122.7, 123.1, 124.1, 127.7, 131.2, 145.9.
1-(1-Nonenyl)-1H-1,2,3-benzotriazole (2h)
Yield: 38%; colorless microcrystals; mp 43–44 °C (Lit.13 15 °C).
13C NMR (75 MHz, CDCl3): d = 110.3, 120.7, 121.3, 122.0, 124.9,
126.8, 128.5, 128.7, 129.3, 131.7, 134.6, 146.6.
1H NMR (300 MHz, CDCl3): d = 0.92 (t, J = 6.9 Hz, 3 H), 1.25–
1.69 (m, 10 H), 2.35 (qd, J = 7.5 Hz, 1.2 Hz, 2 H), 6.54 (dt, J = 14.1,
7.2 Hz, 1 H), 7.30–7.44 (m, 2 H), 7.52–7.58 (m, 1 H), 7.68 (d,
J = 8.4 Hz, 1 H), 8.10 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.0, 22.6, 28.9, 29.0, 29.1, 30.1,
31.7, 110.0, 120.1, 122.7, 123.7, 124.2, 127.8, 131.3, 146.0.
1-[2-(4-Methylphenyl)-1-ethenyl]-1H-1,2,3-benzotriazole (2b)
Yield: 65%; white microcrystals; mp 147–150 °C (Lit.13 148–
151 °C).
1H NMR (300 MHz, CDCl3): d = 2.38 (s, 3 H), 7.21 (d, J = 8.0 Hz,
2 H), 7.39–7.45 (m, 4 H), 7.56 (t, J = 7.8 Hz, 1 H), 7.75 (d, J = 8.4
Hz, 1 H), 7.88 (d, J = 14.7 Hz, 1 H), 8.10 (d, J = 8.4 Hz, 1 H).
Anal. Calcd for C15H21N3: C, 74.04; H, 8.70; N, 17.27. Found: C,
73.76; H, 8.61; N, 17.27.
13C NMR (75 MHz, CDCl3): d = 21.3, 110.0, 120.3, 120.9, 121.1,
124.5, 126.4, 128.1, 129.6, 131.4, 131.4, 138.5, 146.2.
1-(4-Phenyl-1-butenyl)-1H-1,2,3-benzotriazole (2i)
Yield: 41%; colorless microcrystals; mp 127–128 °C.
1-[2-(2-Methylphenyl)-1-ethenyl]-1H-1,2,3-benzotriazole (2c)
Yield: 53%; white microcrystals; mp 101–102 °C.
1H NMR (300 MHz, CDCl3): d = 2.48 (s, 3 H), 7.26–7.29 (m, 3 H),
7.42–7.47 (m, 1 H), 7.57–7.62 (m, 2 H), 7.67–7.83 (m, 3 H), 8.12
(d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 19.9, 109.9, 119.2, 120.3, 122.3,
124.5, 125.3, 126.4, 128.2, 128.4, 130.6, 131.4, 133.3, 136.3, 146.2.
1H NMR (300 MHz, CDCl3): d = 2.61–2.68 (m, 2 H), 2.89 (t,
J = 7.5 Hz, 2 H), 6.47–6.57 (m, 1 H), 7.16–7.40 (m, 7 H), 7.47–
7.58 (m, 2 H), 8.06 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 29.3, 35.1, 109.5, 119.9, 120.5,
124.2, 126.0, 127.7, 128.3, 128.4, 132.7, 140.9, 145.0.
Anal. Calcd for C16H15N3: C, 77.08; H, 6.06; N, 16.85. Found: C,
77.34; H, 6.04; N, 16.65.
Anal. Calcd for C15H13N3: C, 76.57; H, 5.57; N, 17.86. Found: C,
76.50; H, 5.64; N, 18.13.
1-[2-(2-Thienyl)ethenyl]-1H-1,2,3-benzotriazole (2j)
Yield: 53%; white microcrystals; mp 90–92 °C.
1-(1-Butenyl)-1H-1,2,3-benzotriazole (2d)14
Yield: 54%; colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.20 (t, J = 7.5 Hz, 3 H), 2.30–
2.40 (m, 2 H), 6.55 (dt, J = 14.0, 6.9 Hz, 1 H), 7.29 (d, J = 14.2 Hz,
1 H), 7.35–7.41 (m, 1 H), 7.48–7.54 (m, 1 H), 7.65 (d, J = 8.4 Hz,
1 H), 8.06 (d, J = 8.2 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 7.03–7.06 (m, 1 H), 7.17 (d,
J = 3.3 Hz, 1 H), 7.27 (d, J = 4.8 Hz, 1 H), 7.39–7.44 (m, 1 H),
7.53–7.62 (m, 2 H), 7.68–7.79 (m, 2 H), 8.10 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 109.7, 114.5, 120.1, 120.3, 124.5,
125.1, 127.4, 127.7, 128.1, 131.1, 138.1, 145.9.
Anal. Calcd for C12H9N3S: C, 63.41; H, 3.99; N, 18.49. Found: C,
63.64; H, 3.94; N, 18.28.
13C NMR (75 MHz, CDCl3): d = 13.7, 23.6, 110.3, 120.3, 122.5,
124.4, 125.3, 128.0, 131.6, 146.3.
Preparation of 1-(1-Bromovinyl)benzotriazoles 3a–j; General
Procedure
1-(3-Methyl-1-butenyl)-1H-1,2,3-benzotriazole (2e)14
Yield: 64%; colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.20 (d, J = 6.7, 6 H), 2.59–2.66
(m, 1 H), 6.50 (dd, J = 14.4, 7.2 Hz, 1 H), 7.27 (d, J = 14.4 Hz, 1 H),
7.35–7.40 (m, 1 H), 7.48–7.53 (m, 1H), 7.65 (d, J = 8.2 Hz, 1 H),
8.06 (d, J = 8.1 Hz, 1 H).
To a solution of vinylbenzotriazole 2 (11 mmol) in CH2Cl2 (20 mL)
was added Br2 (1.84 g, 11.5 mmol) in CH2Cl2 (5 mL) at 0 °C and the
mixture was stirred at r.t. for 4 h. Et3N (6 mL) was added at 0 °C and
the mixture was stirred at r.t. for 14 h. The reaction mixture was fil-
tered and the filtrate was washed with HCl (1 N, 10 mL), brine (10
mL) and dried over MgSO4. Evaporation of the solvent gave a crude
product that was purified by flash column chromatography (hex-
anes–EtOAc, 19:1).
13C NMR (75 MHz, CDCl3): d = 22.2, 29.4, 110.0, 120.0, 121.0,
124.1, 127.7, 130.1, 131.3, 146.0.
1-[(EZ)-4-Methyl-1-pentenyl]-1H-1,2,3-benzotriazole (2f)
Yield: 51%; colorless oil.
1-(1-Bromo-2-phenyl-1-ethenyl)-1H-1,2,3-benzotriazole (3a)
Yield: 80%; white microcrystals; mp 78–80 °C.
1H NMR (300 MHz, CDCl3): d = 6.75 (d, J = 7.5 Hz, 2 H), 7.18–
7.08 (m, 3 H), 7.51–7.41 (m, 4 H), 8.13 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 108.8, 110.4, 120.4, 124.9, 128.0,
128.7, 128.9, 129.3, 131.8, 132.6, 136.1, 145.6.
1H NMR (300 MHz, CDCl3): d = 1.01 (0.91) (d, J = 6.6 Hz, 6 H),
1.73–1.90 (m, 1 H), 2.19–2.24 (2.31–2.36) (m, 2 H), 6.45–6.55
(5.84–5.92) (m, 1 H), 7.28 (7.04) (d, J = 14.1 Hz, 1 H), 7.37–7.42
(m, 1 H), 7.49–7.55 (7.65–7.67) (m, 2 H), 8.06–8.09 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 22.2, 28.3 (30.8), 39.2 (36.3),
110.0 (109.6), 120.1 (119.8), 122.2 (120.6), 123.4, 124.2 (124.0),
127.8 (127.6), 128.7, 131.3, 146.0 (145.1).
Anal. Calcd for C14H10BrN3: C, 56.02; H, 3.36; N, 14.00. Found: C,
55.98; H, 3.20; N, 13.84.
Anal. Calcd for C12H15N3: C, 71.61; H, 7.51; N, 20.88. Found: C,
71.30; H, 7.54; N, 21.08.
1-[1-Bromo-2-(4-methylphenyl)-1-ethenyl]-1H-1,2,3-benzotria-
zole (3b)
Yield: 61%; white needles; mp 158–160 °C.
1-(1-Pentenyl)-1H-1,2,3-benzotriazole (2g)12
Yield: 59%; yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.00 (t, J = 7.2 Hz, 3 H), 1.52–
1.64 (m, 2 H), 2.28 (dq, J = 7.5 Hz, 1.5 Hz, 2 H), 6.49 (dt, J = 14.4,
1H NMR (300 MHz, CDCl3): d = 2.20 (s, 3 H), 6.61 (d, J = 8.1 Hz,
2 H), 6.89 (d, J = 8.1 Hz, 2 H), 7.37 (s, 1 H), 7.54–7.42 (m, 3 H),
8.13 (d, J = 8.1 Hz, 1 H).
Synthesis 2006, No. 19, 3231–3237 © Thieme Stuttgart · New York

3234
A. R. Katritzky et al.
PAPER
1[(EZ)-1-Bromo-1-nonenyl]-1H-1,2,3-benzotriazole (3h)
13C NMR (75 MHz, CDCl3): d = 21.2, 107.6, 110.5, 120.3, 124.9,
128.8, 129.5, 129.8, 131.8, 136.2, 139.6, 145.6.
Yield: 54%; yellow oil.
Anal. Calcd for C15H12BrN3: C, 57.34; H, 3.85; N, 13.37. Found: C,
57.61; H, 3.70; N, 13.41.
1H NMR (300 MHz, CDCl3): d = 0.82 (0.90) (t, J = 6.6 Hz, 3 H),
1.12–1.25 (m, 7 H), 1.30–1.46 (m, 3 H), 1.93 (2.47) (q, J = 7.5 Hz,
2 H), 6.52 (t, J = 7.8 Hz, 1 H), 7.43–7.47 (m, 1 H), 7.54–7.70 (m,
2 H), 8.08–8.14 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.0 (14.0), 22.5 (22.6), 28.4
(27.9), 28.7 (29.0), 28.8 (29.1), 29.6 (30.6), 31.5 (31.7), 107.3,
110.4 (110.7), 120.2, 124.6 (124.7), 128.5 (128.3), 132.4 (135.2),
139.4, 145.3
1-[1-Bromo-2-(2-methylphenyl)-1-ethenyl]-1H-1,2,3-benzotria-
zole (3c)
Yield: 75%; pale yellow microcrystals; mp 81–82 °C.
1H NMR (300 MHz, CDCl3): d = 2.40 (s, 3 H), 6.48 (d, J = 7.8 Hz,
1 H), 6.70 (t, J = 7.5 Hz, 1 H), 7.01 (t, J = 7.5 Hz, 1 H), 7.09 (d,
J = 7.8 Hz, 1 H), 7.32–7.36 (m, 2 H), 7.42–7.46 (m, 1 H), 7.51 (s,
1 H), 8.03 (d, J = 8.7 Hz, 1 H).
Anal. Calcd for C15H20BrN3: C, 55.91; H, 6.26; N, 13.04. Found: C,
55.82; H, 6.31; N, 13.10.
13C NMR (75 MHz, CDCl3): d = 20.0, 109.7, 110.1, 120.2, 124.6,
126.0, 127.2, 128.6, 128.9, 130.2, 131.9, 134.3, 136.1, 145.3.
1-(1-Bromo-4-phenyl-1-butenyl)-1H-1,2,3-benzotriazole (3i)
Yield: 42%; yellow oil.
Anal. Calcd for C15H12BrN3: C, 57.34; H, 3.85; N, 13.37. Found: C,
57.18; H, 3.75; N, 13.25.
1H NMR (300 MHz, CDCl3): d = 2.23–2.30 (m, 2 H), 2.72, (q,
J = 7.5 Hz, 2 H), 6.50 (t, J = 7.8 Hz, 1 H), 7.02–7.04 (m, 2 H), 7.14–
7.22 (m, 3 H), 7.38–7.43 (m, 2 H), 7.49–7.54 (m, 1 H), 8.08 (d,
J = 8.7 Hz, 1 H).
1-(1-Bromo-1-butenyl)-1H-1,2,3-benzotriazole (3d)
Yield: 52%; yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.02 (t, J = 7.4 Hz, 3 H), 2.00–
1.90 (m, 2 H), 6.52 (t, J = 7.7 Hz, 1 H), 7.48–7.42 (m, 1 H), 7.56–
7.64 (m, 2 H), 8.11 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.5, 23.5, 107.4, 110.7, 120.5,
124.9, 128.9, 132.7, 140.8, 145.6.
13C NMR (75 MHz, CDCl3): d = 31.3, 34.5, 108.1, 110.4, 120.0,
124.6, 126.2, 128.2, 128.4, 128.5, 132.2, 137.8, 139.8, 145.2.
Anal. Calcd for C16H14BrN3: C, 58.55; H, 4.30; N, 12.80. Found: C,
58.76; H, 4.13; N, 12.61.
1-[1-Bromo-2-(2-thienyl)ethenyl]-1H-1,2,3-benzotriazole (3j)
Yield: 52%; white needles; mp 135–136 °C.
1H NMR (300 MHz, CDCl3): d = 6.93 (d, J = 3.6 Hz, 1 H), 7.01 (d,
J = 3.9 Hz, 1 H), 7.42–7.47 (m, 1 H), 7.49–7.61 (m, 2 H), 7.67–7.71
(m, 2 H), 8.10 (d, J = 8.4 Hz, 1 H).
Anal. Calcd for C10H10BrN3: C, 47.64; H, 3.40; N, 16.67. Found: C,
47.63; H, 3.87; N, 16.54.
1-(1-Bromo-3-methyl-1-butenyl)-1H-1,2,3-benzotriazole (3e)
Yield: 49%; brown oil.
1H NMR (300 MHz, CDCl3): d = 1.02 (d, J = 6.6 Hz, 6 H), 2.14–
2.22 (m, 1 H), 6.37 (d, J = 10.3 Hz, 1 H), 7.42–7.49 (m, 1 H), 7.57–
7.66 (m, 2 H), 8.11 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 22.2, 29.9, 106.0, 110.3, 120.2,
124.7, 128.6, 132.5, 145.3, 146.0.
13C NMR (75 MHz, CDCl3): d = 109.8, 112.1, 114.0, 120.5, 120.8,
124.8, 127.8, 128.4, 130.8, 131.3, 139.9, 146.2.
Anal. Calcd for C12H8BrN3S: C, 47.07; H, 2.63; N, 13.72. Found: C,
47.28; H, 2.50; N, 13.43.
Preparation of N-(a-Haloacyl)benzotriazoles 4a–m; General
Procedure
Anal. Calcd for C11H12BrN3: C, 49.64; H, 4.54; N, 15.79. Found: C,
49.29; H, 4.49; N, 15.79.
To a solution of 1-(1-bromovinyl)benzotriazole 3 (2 mmol) in
MeCN–H2O (8:1), NBS (0.35 g, 3 mmol) or NIS (0.88 g, 4 mmol)
was added in one portion. A catalytic amount of conc. HBr (48%, 2
mL) or conc. HI (51%, 2 mL) was then added and the mixture was
stirred at r.t. for 12. The reaction mixture was then diluted with Et2O
(30 mL) and treated dropwise with aqueous sodium thiosulfate until
the yellow color had disappeared. The mixture was then washed
with aq NaHCO3 (10 mL) and brine (10 mL). The organic layer was
dried over MgSO4, filtered and evaporated in vacuo. The crude
product was purified by flash chromatography on silica gel (hex-
anes–EtOAc, 95:5).
1-[(EZ)-1-Bromo-4-methyl-1-pentenyl]-1H-1,2,3-benzotriazole
(3f)
Yield: 56%; brown oil.
1H NMR (300 MHz, CDCl3): d = 0.84 (1.05) (d, J = 6.6 Hz, 6 H),
1.68–1.75 (1.90–1.99) (m, 1 H, i-Pr CH), 1.84 (2.37) (t, J = 7.5 Hz,
2 H, CH2), 6.48–6.56 (m, 1 H), 7.42–7.48 (m, 1 H), 7.56–7.70 (m,
2 H), 8.08–8.13 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 22.1 (22.4), 27.9 (27.9), 38.3
(39.5), 107.7, 110.5 (110.7), 120.3, 124.7 (124.6), 128.6 (128.4),
132.5, 134.1, 138.5, 145.4.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-2-phenyl-1-ethanone
(4a)
Yield: 75%; white microcrystals; mp 118–121 °C.
Anal. Calcd for C12H14BrN3: C, 51.44; H, 5.04; N, 15.00. Found: C,
51.33; H, 4.95; N, 15.37.
1H NMR (300 MHz, CDCl3): d = 7.06 (s, 1 H), 7.43–7.36 (m, 3 H),
7.55–7.50 (m, 1 H), 7.77–7.65 (m, 3 H), 8.11–8.14 (m, 1 H), 8.27–
8.30 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 45.4, 114.7, 120.7, 127.0, 129.3,
129.6, 130.0, 131.2, 131.4, 134.6, 146.6, 166.3.
1-[(EZ)-1-Bromo-1-pentenyl]-1H-1,2,3-benzotriazole (3g)
Yield: 53%; yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.06 (0.84) (t, J = 7.5 Hz, 3 H),
1.58–1.70 (1.38–1.57) (m, 2 H), 2.45 (1.91) (q, J = 7.5 Hz, 2 H),
6.46–6.55 (m, 1 H), 7.40–7.48 (m, 1 H), 7.54–7.61 (m, 1 H), 7.68–
7.70 (m, 1 H), 8.07–8.12 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.7 (13.4), 21.3 (21.7), 32.5
(31.5), 110.7, 120.2, 123.0, 124.6 (124.7), 128.3 (128.6), 135.0,
139.2, 145.5.
Anal. Calcd for C14H10BrN3O: C, 53.19; H, 3.19; N, 13.29. Found:
C, 52.92; H, 3.07; N, 13.17.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-2-(4-methylphenyl)-1-
ethanone (4b)
Yield: 73%; white microcrystals; mp 142–144 °C.
Anal. Calcd for C11H12BrN3: C, 49.64; H, 4.54; N, 15.79. Found: C,
49.29; H, 4.42; N, 15.98.
Synthesis 2006, No. 19, 3231–3237 © Thieme Stuttgart · New York

PAPER
One-Carbon Homologation of Aldehydes to N-(a-Haloacyl)benzotriazoles
3235
1H NMR (300 MHz, CDCl3): d = 2.34 (s, 3 H), 7.05 (s, 1 H), 7.20
(d, J = 8.1 Hz, 2 H), 7.56–7.51 (m, 1 H), 7.71–7.63 (m, 3 H), 8.13
(d, J = 8.2 Hz, 1 H), 8.30 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.3, 45.3, 114.5, 120.5, 126.7,
129.2, 129.8, 130.9, 131.2, 131.4, 139.9, 146.4, 166.1.
13C NMR (75 MHz, CDCl3): d = 13.4, 20.6, 35.8, 43.5, 100.2, 114.5,
120.5, 126.7, 130.9, 146.4, 168.1.
Anal. Calcd for C11H12BrN3O: C, 46.83; H, 4.29; N, 14.89. Found:
C, 46.67; H, 4.72; N, 14.70.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-1-nonanone (4h)
Yield: 61%; yellow oil.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H), 1.28–
1.62 (m, 10 H), 2.20–2.40 (m, 2 H), 5.85 (t, J = 7.5 Hz, 1 H), 7.51–
7.56 (m, 1 H), 7.67–7.72 (m, 1 H), 8.15 (d, J = 8.4 Hz, 1 H), 8.30
(d, J = 8.4 Hz, 1 H).
Anal. Calcd for C15H12BrN3O: C, 54.56; H, 3.66; N, 12.73. Found:
C, 54.50; H, 3.55; N, 12.47.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-2-(2-methylphenyl)-1-
ethanone (4c)
Yield: 71%; pale yellow microcrystals; mp 120–121 °C.
1H NMR (300 MHz, CDCl3): d = 2.62 (s, 3 H), 7.23–7.28 (m, 4 H),
7.52 (t, J = 7.5 Hz, 1 H), 7.67–7.72 (m, 2 H), 8.10 (d, J = 8.4 Hz,
1 H), 8.32 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 19.4, 43.6, 114.4, 120.4, 126.7,
127.0, 128.8, 129.6, 130.9, 131.1, 133.2, 136.5, 146.2, 166.0.
13C NMR (75 MHz, CDCl3): d = 14.0, 22.5, 27.2, 28.8, 28.9, 31.6,
33.9, 43.7, 114.4, 120.4, 126.6, 130.8, 131.1, 146.4, 168.0.
Anal. Calcd for C15H20BrN3O: C, 53.26; H, 5.96; N, 12.42. Found:
C, 52.78; H, 6.00; N, 11.54.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-4-phenyl-1-butanone
(4i)
Yield: 77%; yellow oil.
Anal. Calcd for C15H12BrN3O: C, 54.56; H, 3.66; N, 12.73. Found:
C, 54.55; H, 3.51; N, 12.78.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-1-butanone (4d)
Yield: 67%; white microcrystals; mp 59–63 °C.
1H NMR (300 MHz, CDCl3): d = 1.18 (t, J = 7.2 Hz, 3 H), 2.44–
2.24 (m, 2 H), 5.79 (t, J = 7.5 Hz, 1 H), 7.55 (t, J = 7.8 Hz, 1 H),
7.71 (t, J = 7.5 Hz, 1 H), 8.16 (d, J = 8.1 Hz, 1 H), 8.30 (d, J = 8.1
Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 2.53–2.73 (m, 2 H), 2.79–3.01 (m,
2 H), 5.79 (t, J = 7.2 Hz, 1 H), 7.15–7.29 (m, 5 H), 7.52 (t, J = 7.2
Hz, 1 H), 7.67 (t, J = 7.2 Hz, 1 H), 8.13 (d, J = 8.4 Hz, 1 H), 8.25 (d,
J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 33.3, 35.4, 43.2, 114.5, 120.5,
126.6, 126.7, 128.5, 128.7, 130.9, 131.1, 139.6, 146.4, 167.8.
13C NMR (75 MHz, CDCl3): d = 11.9, 27.4, 45.4, 114.4, 120.4,
126.6, 130.8, 131.0, 146.4, 167.9.
Anal. Calcd for C16H14BrN3O: C, 55.83; H, 4.10; N, 12.21. Found:
C, 56.07; H, 3.96; N, 11.97.
Anal. Calcd for C10H10BrN3O: C, 44.80; H, 3.76; N, 15.67. Found:
C, 44.02; H, 3.58; N, 14.41.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-iodo-1-pentanone (4k)
Yield: 69%; brown oil.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-3-methyl-1-butanone
(4e)
Yield: 53%; yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.16 (d, J = 6.6 Hz, 3 H), 1.28 (d,
J = 6.6 Hz, 3 H), 2.54–2.64 (m, 1 H), 5.71 (d, J = 8.1 Hz, 1 H),
7.53–7.58 (m, 1 H), 7.68–7.73 (m, 1 H), 8.16 (d, J = 8.4 Hz, 1 H),
8.32 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 20.1, 20.2, 31.9, 51.9, 114.5, 120.4,
126.7, 130.8, 131.1, 146.4, 167.8.
1H NMR (300 MHz, CDCl3): d = 1.03 (t, J = 7.5 Hz, 3 H), 1.43–
1.68 (m, 2 H), 2.25 (q, J = 7.5 Hz, 2 H), 5.99 (t, J = 7.5 Hz, 1 H),
7.52–7.58 (m, 1 H), 7.68–7.73 (m, 1 H), 8.14 (d, J = 8.4 Hz, 1 H),
8.27 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.2, 19.2, 22.6, 36.8, 114.4, 120.3,
126.4, 130.6, 131.1, 146.4, 169.6.
Anal. Calcd for C11H12IN3O: C, 40.14; H, 3.67; N, 12.77. Found: C,
40.53; H, 3.52; N, 12.56.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-iodo-1-nonanone (4l)
Yield: 53%; brown oil.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H), 1.28–
1.60 (m, 10 H), 2.23–2.31 (m, 2 H), 5.97 (t, J = 7.5 Hz, 1 H), 7.51–
7.56 (m, 1 H), 7.67–7.72 (m, 1 H), 8.15 (d, J = 8.4 Hz, 1 H), 8.28
(d, J = 8.1 Hz, 1 H).
Anal. Calcd for C11H12BrN3O: C, 46.83; H, 4.29; N, 14.89. Found:
C, 46.66; H, 4.71; N, 14.70.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-4-methyl-1-pentanone
(4f)
Yield: 70%; pale yellow microcrystals; mp 59–60 °C.
1H NMR (300 MHz, CDCl3): d = 1.03 (dd, J = 6.6, 2.1 Hz, 6 H),
1.84–1.98 (m, 1 H), 2.20 (t, J = 7.2 Hz, 2 H), 5.94 (t, J = 7.5 Hz,
1 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.71 (t, J = 8.1 Hz, 1 H), 8.16 (d,
J = 8.1 Hz, 1 H), 8.30 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.7, 22.5, 26.4, 42.3, 42.4, 114.4,
120.4, 126.6, 130.8, 131.1, 146.4, 168.1.
13C NMR (75 MHz, CDCl3): d = 14.0, 19.5, 22.5, 28.7, 28.9, 29.3,
31.6, 35.0, 114.5, 120.3, 126.5, 130.7, 131.1, 146.5, 169.7.
Anal. Calcd for C15H20IN3O: C, 46.77; H, 5.23; N, 10.91. Found: C,
46.96; H, 5.23; N, 10.69.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-iodo-4-phenyl-1-butanone
(4m)
Anal. Calcd for C12H14BrN3O: C, 48.67; H, 4.76; N, 14.19. Found:
C, 48.81; H, 4.68; N, 13.78.
Yield: 64%; brown oil.
1H NMR (300 MHz, CDCl3): d = 2.58 (q, J = 7.5 Hz, 2 H), 2.72–
2.95 (m, 2 H), 5.91 (t, J = 7.5 Hz, 1 H), 7.15–7.29 (m, 5 H), 7.48–
7.53 (m, 1 H), 7.64–7.69 (m, 1 H), 8.12 (d, J = 8.1 Hz, 1 H), 8.24
(d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 18.7, 35.2, 36.6. 114.4, 120.3,
126.5, 128.4, 128.6, 130.6, 131.1, 139.4, 146.4, 169.4.
1-(1H-1,2,3-Benzotriazol-1-yl)-2-bromo-1-pentanone (4g)
Yield: 58%; yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.03 (t, J = 7.2 Hz, 3 H), 1.49–
1.72 (m, 2 H), 2.20–2.40 (m, 2 H), 5.86 (t, J = 7.5 Hz, 1 H), 7.53–
7.59 (m, 1 H), 7.68–7.74 (m, 1 H), 8.16 (d, J = 8.4 Hz, 1 H), 8.30
(d, J = 8.4 Hz, 1 H).
HRMS calcd for C16H14IN3O [M + H]+: 392.0260; found: 392.0208.
Synthesis 2006, No. 19, 3231–3237 © Thieme Stuttgart · New York

3236
A. R. Katritzky et al.
PAPER
Preparation of N-(a-Haloacyl)amides and Esters 5a–h; General
Procedure
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.0 Hz, 3 H), 1.26 (br
s, 10 H), 1.93–1.95 (m, 2 H), 2.33 (s, 3 H), 2.79 (t, J = 6.6 Hz, 2 H),
3.47–3.56 (m, 2 H), 4.17 (t, J = 7.2 Hz, 1 H), 5.95 (br s, 1 H), 7.11
(s, 4 H).
13C NMR (75 MHz, CDCl3): d = 14.1, 21.0, 22.6, 27.1, 28.7, 29.0,
29.4, 31.7, 34.9, 36.9, 41.2, 128.7, 129.3, 135.4, 136.1, 170.1.
To a solution of N-(a-haloacyl)benzotriazole 4 (0.1 g, 0.33 mmol)
and Et3N (0.03 g, 0.66 mmol) in CH2Cl2 (5 mL) was added a soln of
nucleophile (1 equiv) in CH2Cl2 (5 mL) at 0 °C and the mixture was
stirred at r.t. for 4 h. The mixture was diluted with CH2Cl2 (20 mL)
and washed with H2O (5 mL), brine (5 mL) and dried over MeSO4.
Filtration and evaporation of the solvent gave the crude product
which was purified by flash column chromatography (EtOAc–hex-
anes, 4:6).
Anal. Calcd for C18H28INO: C, 53.87; H, 7.03; N, 3.49. Found: C,
54.06; H, 6.96; N, 3.47.
N-(1-Phenylethyl)-2-bromo-4-methylpentanamide (5g)
Yield: 61%; white microcrystals; mp 78–79 °C.
N-Benzyl-2-bromo-2-phenylacetamide (5a)
Yield: 87%; colorless microcrystals; mp 90–91 °C (Lit.16 95–
96 °C).
1H NMR (300 MHz, CDCl3): d = 4.47 (d, J = 5.4 Hz, 2 H), 5.47 (s,
1 H), 7.08 (br s, 1 H), 7.25–7.46 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 44.3, 51.2, 127.6, 127.7, 128.3,
128.7, 128.9, 129.1, 137.2, 137.3, 167.1.
1H NMR (300 MHz, CDCl3): d = 0.89–0.97 (m, 6 H), 1.50 (dd,
J = 6.9, 2.4 Hz, 3 H), 1.79–1.97 (m, 3 H), 4.28–4.36 (m, 1 H), 5.08
(quin, J = 7.2 Hz, 1 H), 6.62 (br s, 1 H), 7.24–7.38 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 21.0, 21.6, 21.7, 22.7, 26.4, 44.5,
49.4, 49.5, 50.5, 126.0, 126.1, 127.5, 127.6, 128.8, 142.6, 168.2.
Anal. Calcd for C14H20BrNO: C, 56.38; H, 6.76; N, 4.70. Found: C,
56.25; H, 6.81; N, 4.51.
N-Benzyl-2-bromo-4-methylpentanamide (5b)
Yield: 75%; colorless microcrystals; mp 66–67 °C.
Benzyl 2-Iodopentanoate (5h)
1H NMR (300 MHz, CDCl3): d = 0.91 (d, J = 6.0 Hz, 3 H), 0.96 (d,
J = 6.3 Hz, 3 H), 1.77–1.98 (m, 3 H), 4.35 (dd, J = 9.0, 5.4 Hz, 1 H),
4.44 (d, J = 5.7 Hz, 2 H), 6.77 (br s, 1 H), 7.26–7.36 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 20.9, 22.7, 26.3, 44.0, 44.5, 50.3,
127.6, 127.7, 128.8, 137.5, 169.0.
Yield: 82%; colorless gel.
1H NMR (300 MHz, CDCl3): d = 0.92 (t, J = 7.5 Hz, 3 H), 1.25–
1.48 (m, 2 H), 1.97 (q, J = 7.5 Hz, 2 H), 4.35 (t, J = 7.5 Hz, 1 H),
5.17 (s, 2 H), 7.33–7.37 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 13.1, 20.8, 22.6, 37.9, 67.4, 128.2,
128.4, 128.6, 135.2, 171.3.
Anal. Calcd for C13H18BrNO: C, 54.94; H, 6.38; N, 4.93. Found: C,
55.24; H, 6.67; N, 4.81.
Anal. Calcd for C12H15IO2: C, 45.30; H, 4.75; N, 0.0. Found: C,
44.95; H, 4.63; N, 0.37.
N-Phenethyl-2-bromo-4-methylpentanamide (5c)
Yield: 69%; white microcrystals; mp 73–75 °C (Lit.17 76 °C).
Acknowledgment
1H NMR (300 MHz, CDCl3): d = 0.89 (d, J = 5.7 Hz, 3 H), 0.94 (d,
J = 6.0 Hz, 3 H), 1.74–1.92 (m, 3 H), 2.84 (t, J = 6.3 Hz, 2 H), 3.53
(q, J = 6.3 Hz, 2 H), 4.26 (dd, J = 8.7, 5.1 Hz, 1 H), 6.40 (br s, 1 H),
7.19–7.32 (m, 5 H).
We thank Dr. Dennis C. Hall for helpful discussions.
References
13C NMR (75 MHz, CDCl3): d = 21.0, 22.6, 26.3, 35.4, 41.1, 44.6,
50.3, 126.6, 128.6, 128.8, 138.4, 169.0.
(1) (a) Katritzky, A. R.; Suzuki, K.; Wang, Z. Synlett 2005,
1656. (b) Katritzky, A. R.; Pastor, A. J. Org. Chem. 2000,
65, 3679. (c) Wang, X.; Zhang, Y. Tetrahedron Lett. 2002,
43, 5431. (d) Katritzky, A. R.; Meher, N. K.; Singh, S. K. J.
Org. Chem. 2005, 70, 7792. (e) Katritzky, A. R.; Fang, Y.;
Donkor, A.; Xu, J. Synthesis 2000, 2029. (f) Katritzky, A.
R.; Abdel-Fattah, A. A. A.; Akhmedova, R. G. Arkivoc
2005, (vi), 329. (g) Katritzky, A. R.; Suzuki, K.; Singh, S.
K.; He, H.-Y. J. Org. Chem. 2003, 68, 5720. (h) Katritzky,
A. R.; Suzuki, K.; Singh, S. K. Croat. Chem. Acta 2004, 77,
175.
(2) (a) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org. Chem.
2000, 65, 8210. (b) Katritzky, A. R.; Wang, M.; Yang, H.;
Zhang, S.; Akhmedov, N. G. Arkivoc 2002, (viii), 134.
(c) Katritzky, A. R.; Yang, H.; Zhang, S.; Wang, M. Arkivoc
2002, (xi), 39. (d) Katritzky, A. R.; Suzuki, K.; Singh, S. K.
Synthesis 2004, 2645. (e) Katritzky, A. R.; Hoffmann, S.;
Suzuki, K. Arkivoc 2004, (xii), 14.
(3) Karitzky, A. R.; Pastor, A.; Voronkov, M. V. J. Heterocycl.
Chem. 1999, 36, 777.
(4) Baradarani, M. M.; Khalafy, J.; Prager, R. H. Aust. J. Chem.
1999, 52, 775.
(5) Katritzky, A. R.; Cai, C.; Suzuki, K.; Singh, S. K. J. Org.
Chem. 2004, 69, 811.
(6) Katritzky, A. R.; Shestopalov, A. A.; Suzuki, K. Synthesis
2004, 1806.
N-(4-Methylphenethyl)-2-bromo-4-methylpentanamide (5d)
Yield: 63%; white microcrystals; mp 89–90 °C.
1H NMR (300 MHz, CDCl3): d = 0.89 (d, J = 6.3 Hz, 3 H), 0.94 (d,
J = 6.3 Hz, 3 H), 1.77–1.94 (m, 3 H), 2.32 (s, 3 H), 2.79 (t, J = 6.9
Hz, 2 H), 3.51 (q, J = 6.6 Hz, 2 H), 4.26 (dd, J = 9.3, 5.4 Hz, 1 H),
6.37 (br s, 1 H), 7.08–7.14 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 21.0, 22.6, 26.3, 34.9, 41.3, 44.6,
50.4, 128.7, 129.3, 135.3, 136.1, 169.0.
Anal. Calcd for C15H22BrNO: C, 57.70; H, 7.10; N, 4.49. Found: C,
58.07; H, 7.29; N, 4.67.
N-(4-Methylphenethyl)-2-iodopentanamide (5e)
Yield: 56%; white microcrystals; mp 80–81 °C.
1H NMR (300 MHz, CDCl3): d = 0.91 (t, J = 7.5 Hz, 3 H), 1.26–
1.45 (m, 2 H), 1.92 (q, J = 7.5 Hz, 2 H), 2.33 (s, 3 H), 2.79 (t,
J = 6.9 Hz, 2 H), 3.47–3.56 (m, 2 H), 4.19 (t, J = 7.2 Hz, 1 H), 5.95
(br s, 1 H), 7.09–7.15 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 13.1, 21.0, 22.6, 26.7, 34.9, 38.8,
41.2, 128.7, 129.3, 135.4, 136.1, 170.1.
Anal. Calcd for C14H20INO: C, 48.71; H, 5.89; N, 4.06. Found: C,
49.08; H, 5.94; N, 3.85.
(7) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003,
N-(4-Methylphenethyl)-2-iodononanamide (5f)
Yield: 76%; white microcrystals; mp 84–85 °C.
2795.
Synthesis 2006, No. 19, 3231–3237 © Thieme Stuttgart · New York

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One-Carbon Homologation of Aldehydes to N-(a-Haloacyl)benzotriazoles
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(8) Katritzky, A. R.; Shobana, N.; Juliusz, P.; Pernak, J.; Afridi,
(13) Katritzky, A. R.; Rachwal, S.; Caster, K. C.; Mahni, F. J.
Chem. Soc., Perkin Trans. 1 1987, 781.
(14) Katritzky, A. R.; Jiang, R.; Sommen, G. L.; Singh, S. K.
Arkivoc 2004, (ix), 44.
(15) Katritzky, A. R.; Ferwanah, A. S.; Denisenko, S. N.
Heterocycles 1999, 50, 767.
(16) Hoffman, R. V.; Nayyar, N. K.; Chen, W. J. Org. Chem.
1992, 57, 5700.
(17) Braun, J.; Munch, W. Ber. Dtsch. Chem. Ges. B 1927, 60,
A. S.; Fan, W.-Q. Tetrahedron 1992, 48, 7817.
(9) Harpp, D. N.; Bao, L. Q.; Black, C. J.; Gleason, J. G.; Smith,
R. A. J. Org. Chem. 1975, 40, 3420; and references cited
therein.
(10) Kwart, H.; Scalzi, F. V. J. Am. Chem. Soc. 1964, 86, 5496.
(11) Cook, A. G.; Fields, E. K. J. Org. Chem. 1962, 27, 3686.
(12) Katritzky, A. R.; Offerman, R. J.; Cabildo, P.; Soleiman, M.
Recl. Trav. Chim. Pays-Bas 1988, 107, 641.
345.
Synthesis 2006, No. 19, 3231–3237 © Thieme Stuttgart · New York