A mild and efficient method for formation of C-N bond from benzyl alcohols and sulfonamide, carboxamide, 4-nitroanline and azide catalysed by SnCl 4

Article abstract of DOI:10.3184/030823410X12831036379628

A mild and efficient method for the formation of C-N bonds is reported with SnCl₄ as an inexpensive catalyst. With 10 mol% of SnCl₄, the direct substitution reaction of secondary benzyl alcohols with a sulfonamide, a carboxamide, 4-nitroaniline and an azide proceeds well in good to excellent yields at room temperature.

Full text of DOI:10.3184/030823410X12831036379628

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 511
SEPTEMBER, 511–513
A mild and efficient method for formation of C–N bond from benzyl
alcohols and sulfonamide, carboxamide, 4-nitroanline and azide catalysed
by SnCl4
Lingjun Li*, Anlian Zhu, Huiwen Yao, Yujing Wei, Di Yang, Jianping Li and Guisheng Zhang
College of Chemistry and Environmental Science, Henan Normal University, Key Laboratory of Green Chemical Media and Reactions,
Ministry of Education, XinXiang 453007, P. R. China
A mild and efficient method for the formation of C–N bonds is reported with SnCl4 as an inexpensive catalyst. With
10 mol% of SnCl4, the direct substitution reaction of secondary benzyl alcohols with a sulfonamide, a carboxamide,
4-nitroaniline and an azide proceeds well in good to excellent yields at room temperature.
Keywords: C–N bond formation, benzyl alcohol, p-toluenesulfonamide, p-nitroaniline, tetramethylsilylazide
The formation of C–N bonds is an important reaction in organic
synthesis.1 The traditional method for formation of C–N bonds
always produces stoichiometric amounts of salt waste in the
derivatisation of the alcohol and C–N bond formation steps.2,3
Recently the direct catalytic substitution of alcohols with N-
nucleophiles has aroused interest due to its atomic economy
and environmental advantages.2–6 Several catalysts have been
developed for this transformation in the literature, such as
first, but no desirable product was found at room temperature
or at reflux (Entries 1, 2 in Table 1). AlCl3 was then tried, and
50% yield of 3a was given at room temperature, but the high
reaction temperature could not improve the yield of 3a (entries
3, 4 in Table 1). SnCl4 is an inexpensive Lewis acid and has
been applied as the catalyst for the Ferrier rearrangement,11
glycosylation reaction12 and C–C bond construction.13 Here we
found SnCl4 (10 mol% of the alcohol) in CH2Cl2 could effi-
ciently catalyse the direct substitution reaction between 1a and
2a to give 3a in 95% yield within 16 hours at room tempera-
ture (Entry 5 in Table 1). Moreover, BF3·OEt2 could only
catalyse this reaction with 77% yield which was less than the
yield in the case of SnCl4 (entry 6 in Table 1). Other Lewis acid
catalysts such as FeCl3·6H2O and Fe2 (SO4)3·xH2O did not
catalyse this reaction (entries 7–9 in Table 1).
6
NaAuCl4,4 H-montmorillonite,5 Bi (OTf)3/KPF6,3 CoCl5 and
2
FeCl3. But the in these cases, high reaction temperatures,
complex catalytic systems or expensive metals are usually
involved. In line with our efforts on the methodologies of con-
struction of C-X bonds,7–10 we report here a mild and efficient
method for formation of C–N bond from benzylic alcohols and
N-nucleophiles catalysed by SnCl4.
We took the reaction between benzhydryl alcohol 1a and
p-toluenesulfonamide 2a as an example for the investigation of
catalysts for the formation of the C–N bond from alcohols and
N-nucleophiles (Scheme 1). ZnCl2 was applied in this reaction
Based on the results in Table 1, applications of the SnCl4-
catalysed direct substitutions with secondary benzyl alcohols
and other N-nucleophiles were attempted (Table 2). The N-
nucleophiles, including 4-nitroaniline, carboxamide, azide
Scheme 1 the catalytic reaction between benzhydryl alcohol and p-toluenesulfonamide.
Table 1 Direct catalytic reaction of benzhydryl alcohol with p-toluenesulfonamide with different Lewis acid catalysts
Entry
Catalysta
Reaction time /h
Temperature
Yield of 3ab/%
1
2
3
4
5
6
7
8
9
ZnCl2
24
24
24
24
16
16
24
24
24
RT
Reflux
RT
Reflux
RT
RT
RT
Reflux
Reflux
0
0
50
45
95
77
0
ZnCl2
AlCl3
AlCl3
SnCl4
BF3·OEt2
FeCl3·6H2O
FeCl3·6H2O
Fe2 (SO4)3·xH2O
0
0
RT, Room temperature.
a 10 mol% catalyst was used. b Isolated yield.
* Correspondent. E-mail: lingjunlee@yahoo.com.cn

512 JOURNAL OF CHEMICAL RESEARCH 2010
Table 2 The direct substitution reactions of alcohols with N-nucleophiles catalysed by SnCl4 at room temperature
Entry
1
Alcohol
Nucleophile
Product
Time /h
Yielda/%
95
TsNH2
16
2a
2
3
4
5
6
TsNH2
18
16
16
18
16
85
69
93
71
88
2a
TsNH2
2a
BzNH2
2b
BzNH2
2b
4-NO2C6H4NH2
2c
7
8
4-NO2C6H4NH2
16
85
2c
TMSN3
2d
16
10
91
90
9
TMSN3
2d
a Isolated yield.

JOURNAL OF CHEMICAL RESEARCH 2010 513
NMR (CDCl3, 100 MHz) δ: 166.1, 142.9, 134.8, 130.9, 129.0, 127.9,
127.3, 126.8, 126.1, 50.0, 20.8.
were also investigated for this direct amidation reaction, and
good to excellent yields of product were obtained (entries 4–10
in Table 2). Additionally, benzhydryl alcohols with electron-
withdrawing groups or electron-donating groups and benzyl
alcohols also reacted smoothly with the N-nucleophiles with
good yields (entries 2, 3, 5, 7, 9, in Table 2). It was also estab-
lished that in the absence of SnCl4 no products were formed
from the benzyl alcohol with aniline, benzylamine, benzamide
nor TMS azide after 24h at ambient temperatures.
In brief, a mild and efficient method for formation of C–N
bond is reported with SnCl4 as a catalyst. With 10 mol% of
SnCl4, the direct substitution reaction of secondary benzyl
alcohols with a sulfonamide, a carboxamide, amines and an
azide proceeded well in good yields at room temperature. The
further application of this method to the efficient synthesis of
designed drugs is now being undertaken in our laboratory.
N-(4-nitrophenyl)-1,1’-diphenyl) methylamine (3f): The physical
data shown below were comparable to those reported.4 m.p. 194–
1
195°C, Reported m.p. 195°C; H NMR (400 MHz, CDCl3) δ: 8.07–
8.03 (m, 2H), 7.40–7.31 (m, 10H), 6.54–6.51 (m, 2H), 5.66 (d, J = 4
Hz, 1H), 5.02 (br, 1H); 13C NMR (CDCl3, 100 MHz) δ: 152.7, 141.3,
139.1, 129.7, 128.5, 127.7, 127.0, 112.7, 63.1.
N-(4-nitrophenyl)-1-phenyl-1’-(4-chlorophenyl)methylamine (3g):
The physical data shown below were comparable to those reported.4
m.p. 120–121°C, Reported m.p. 121°C; 1H NMR (400 MHz, CDCl3)
δ: 8.06 (d, J = 8.8 Hz, 2H), 7.73–7.24 (m, 9H), 6.51 (d, J = 8.6 Hz,
2H), 5.52 (d, J = 4.8 Hz, 1H), 5.01 (br, 1H); 13C NMR (CDCl3, 100
MHz) δ: 150.7, 140.1, 138.8, 138.1, 132.9, 129.3, 129.0, 128.1, 127.8,
126.3, 125.2, 110.8, 60.9.
1,1’-Diphenylazidomethane (3h): The physical data shown below
were comparable to those reported.4 1H NMR (400 MHz, CDCl3) δ:
7.52–7.40 (m, 10H), 5.65 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ:
69.7, 128.0, 129.3, 129.7, 140.7; IR (KBr) ν: 2119, 1620, 1521, 1450,
1300, 1170, 819, 697, 561 cm−1; ESI-MS (m/z): 210.1 (M+H)+.
1-Phenyl-1’-(4-methoxyphenyl)azidomethane (3i): The physical
data shown below were comparable to those reported.4 1H NMR (400
MHz, CDCl3) δ: 7.37–7.21 (m, 9H), 5.68 (s, 1H), 3.78 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ: 158.7, 139.7, 132.1, 129.7, 129.5, 128.9,
128.1, 113.7, 67.5, 55.1; IR (KBr) ν:2990, 2852, 2105, 1578, 1455,
1250, 1197, 901, 699, 532; ESI-MS (m/z): 240.1 (M+H)+.
Experimental
Melting points were measured in a Kofler micro-melting point appa-
ratus and were uncorrected. IR spectra were recorded on a Bruker
Vector 22 spectrometer in KBr with frequency in cm−1. 1H NMR spec-
tra were determined on a Bruker AC 400 spectrometer as CDCl3 solu-
tions. Chemical shifts were expressed in ppm downfield from the
internal standard tetramethylsilane. All reagents were obtained from
commercial sources and used without further purification.
This study was supported by the National Natural Sciences
Foundation of China (Grant No. 20802017), the program for
Innovative Research Team (in Science and Technology) in
University of Henan Province (2008IRTSTHN002) and the
Natural Sciences Foundation of Henan Province
(0111010680).
The direct substitution reaction of alcohols and N-nucleophile: A
mixture of SnCl4 (0.1 mmol), alcohol 1 (1 mmol), and N-nucleophile
2 (1.2 mmol) in CH2Cl2 (10 mL) was stirred under air at room tem-
perature for 16 h until complete consumption of alcohol as judged by
TLC. Then saturated NaHCO3 (10 mL) was added into the reaction
mixture. After the conventional workup, the residue of the organic
phase was purified by column chromatography (petroleum ether/ ethyl
acetate) to give products 3.
N-benzhydryl-p-toluenesulfonamide (3a): The physical data shown
below were comparable to those reported.4 m.p. 157–158 °C, Reported
m.p.157°C; 1H NMR (400 MHz, CDCl3) δ: 7.56 (d, J = 8.2 Hz, 2H),
7.21–7.07 (m, 12H), 5.61 (d, J = 7.2 Hz, 1H), 5.21 (d, J = 7.2 Hz, 1H),
2.5 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.2, 142.6, 140.3, 132.5,
131.2, 130.5, 130.3, 130.1, 60.2, 23.1.
Received 7 June 2010; accepted 23 July 2010
Paper 1000181 doi: 10.3184/030823410X12831036379628
Published online: 7 October 2010
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