New heteroaromatic azo compounds based on pyridine, isoxazole, and benzothiazole for efficient and highly selective amidation and mono-N-benzylation of amines under Mitsunobu conditions

Article abstract of DOI:10.1246/bcsj.20090269

4,4′-Azopyridine (2c) is used in conjunction with triphenylphosphine for the efficient conversion of carboxylic acids into amides via Mitsunobu reaction with primary and secondary aliphatic and aromatic amines. The highly selective amidation of only primary aromatic amines with new heterogeneous azo compounds based on benzothiazole 2d and isoxazole 2e is also described. These azo compounds 2c-2e can also be applied for selective mono-N-benzylation of primary aromatic amines. The solid side product heteroaromatic hydrazines obtained under the developed Mitsunobu conditions are easily separated by simple filtration and can be reoxidized to azo compounds for further use.

Full text of DOI:10.1246/bcsj.20090269

©
2010 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 83, No. 8, 923–934 (2010)
923
New Heteroaromatic Azo Compounds Based on Pyridine, Isoxazole, and
Benzothiazole for Efficient and Highly Selective Amidation and
Mono-N-Benzylation of Amines under Mitsunobu Conditions
Nasser Iranpoor,* Habib Firouzabadi,* and Dariush Khalili
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Received October 7, 2009; E-mail: iranpoor@susc.ac.ir
4,4¤-Azopyridine (2c) is used in conjunction with triphenylphosphine for the efficient conversion of carboxylic
acids into amides via Mitsunobu reaction with primary and secondary aliphatic and aromatic amines. The highly selective
amidation of only primary aromatic amines with new heterogeneous azo compounds based on benzothiazole 2d and
isoxazole 2e is also described. These azo compounds 2c­2e can also be applied for selective mono-N-benzylation of
primary aromatic amines. The solid side product heteroaromatic hydrazines obtained under the developed Mitsunobu
conditions are easily separated by simple filtration and can be reoxidized to azo compounds for further use.
Development of simple, efficient, and useful methods for the
and more efficient methodologies to introduce a nitrogen
moiety in a synthetic sequence will always be a major issue of
interest. One chemical transformation that has received
attention in organic synthesis is the Mitsunobu reaction. The
Mitsunobu reaction provides an extremely useful and versatile
easy synthesis of organic compounds using readily available
reagents is one of the major research demands in organic
synthesis. Among these, C­N bond formation is one of the
most significant transformations in organic synthesis. Amides
and amines are significant classes of compounds owing to their
versatility as building blocks and intermediate in organic
2
2
synthetic method for a large array of products.
The
Mitsunobu protocol involves activation of alcohols for attack
by a range of acidic pronucleophiles NuH to form accumu-
lation product RNu which contains the newly formed C­X
bond (X = C, O, N, S, and halogens) using the combination of
an azodicarboxylate and a phosphine. However, the use of this
method is complicated by the resulting complex reaction
mixtures containing product, triphenylphosphine oxide and
the reduced azodicarboxylate, as well as unreacted starting
material. Herein we wish to report a simple, convenient, and
efficient method for amidation and selective N-monoalkylation
of aromatic amines using hetero aryl azo compounds as new,
easily prepared and stable reagents in the Mitsunobu reaction.
In spite of widespread use, the original Mitsunobu reaction
employing diethyl azodicarboxylate (DEAD) and triphenyl-
phosphine (TPP) has a serious drawback: the difficulty
involved in isolating the pure product from a crude reaction
mixture containing excess and spent reagents, specifically
phosphine oxide, hydrazine from reduced azodicarboxylate,
and unconsumed acidic substrate NuH. So an assortment of
approaches has surfaced for tackling the separation problems in
1
synthesis and also in chemical industrial processes. Some
derivatives of amides exhibit biological properties such as
antitumor, anthelmintic, antihistamine, antifungal, and anti-
2
bacterial activity. Synthesis of these compounds has mainly
been achieved by classical chemical reactions, which generally
involve the generation of a reactive carboxy derivative, either
an acid chloride, anhydride, or acyl azide,3 followed by
aminolysis with an amine, due to the low activity of carboxylic
acids. More recently, new systems were developed for facile
4
synthesis of amides using carbonyl diimidazole, isocyanides,
5
6
and carboxylic acids in methanol, Staudinger ligation, micro-
7
wave activation, N-reductive alkylation followed by acyla-
tion, and catalytic systems.9 Besides, due to the synthetic
utility of amines, reactions of amines have been a topic of
immense research interest.10 Also, the alkylation of primary
amines to secondary or tertiary amines is one of the most
fundamental reactions in organic synthesis. Alkylation with
alkyl halides or similar alkylating agents is the most conven-
tional and well-known method,11 but it generates salts as
by-products and exhibits often low chemical selectivity. In
addition, other approaches that are employed to obviate this
problem are the use of catalytic systems in the presence of
alcohols, such as ruthenium, rhodium, iridium, zinc, palladium,
8
2
3
the Mitsunobu reaction and these approaches have recently
2
4
been reviewed. Furthermore, DEAD is an explosive, photo-
sensitive, toxic, shock sensitive, and thermally unstable reagent,
2
5
which may cause cancer or mutation. In order to diminish
these complications and in connection with our ongoing project
aiming at the development and alteration of Mitsunobu
12­18
£
-alumina, KF/Al O ,
compounds,
reductive amination of carbonyl
and amide reduction.20 In many cases direct
2
3
1
2a,19
2
6
N-monoalkylation of amines is either unsatisfactory or not
possible because subsequent alkylation occurs and cannot be
readily prevented. Moreover, toxicity of such alkylating agents
can be problematic.21 For these reasons, the expansion of new
reactions, we recently reported azo pyridines as new, efficient,
and possible alternatives to standard Mitsunobu esterification
2
7
reagents. In continuation of our earlier work, we report herein
an efficient method using azopyridine 2c for amidation of
Published on the web July 15, 2010; doi:10.1246/bcsj.20090269

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Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
Amidation and Mono-N-Benzylation of Amines
NaOCl
2
c (1.3 equiv),
Ar-NH2
a-e
Ar-N=N-Ar
0
°C
PPh (1.3 equiv)
CH CN, reflux
1
2a-e
RNHR' + R''COXH
.2 equiv 1 equiv
3
R''CXN(R)R'
3
1
N
N
N
S
N
O
,
, N
,
,
Ar =
X = O, S
Me
a
b
c
d
e
R = alkyl, aryl
R' = H, alkyl
R'' = alkyl, aryl
Scheme 1.
aliphatic and aromatic amines with carboxylic acids. In addi-
tion, the use of heterogeneous new hetero aryl azo compounds
Scheme 2.
2
d and 2e for highly selective acylation and mono-N-
corresponding benzanilides, which indicated the procedure
accommodates a wide range of substrates. The results are listed
in Table 1.
benzylation of only primary aromatic amines is reported.
Results and Discussion
The scope of this efficient reaction was explored with
various electron-deficient and electron-rich acids and amines.
Yields varied depending on the electronic nature of the
substituents on both the acid and the amine. From Table 1 it
was found that for most cases better results were observed for
the reaction of electron-poor aromatic acids with activated
aromatic amines carrying electron-donating substituents. For
instance, reaction of p-methylbenzoic acid with aniline
proceeded to afford the desired product 3a in 77% (Table 1,
Entry 1), while 86% and 94% yield of products 3b and 3c were
obtained, respectively, when benzoic or p-nitrobenzoic acid
were employed in the reaction (Table 1, Entries 2 and 3). As
expected, anilines with an electron-donating group gave much
better results. Treatment of p-methoxyaniline and benzoic acid
led to a clean reaction affording the desired amide product 3d
in excellent yield (Table 1, Entry 4). The reaction of electron-
deficient anilines such as p-chloro- and p-nitroaniline (Table 1,
Entries 7 and 8) gave the corresponding amide 3g and 3h in
lower yields of 85% and 70%, respectively. Also, a perceptible
dependence of reaction durations on electronic factors is
noteworthy. For the reactions in refluxing acetonitrile, the
unsubstituted benzoic acid (Table 1, Entry 2) or acids that carry
electron-withdrawing groups (Table 1, Entries 3 and 11), and
also aniline (Table 1, Entry 3) and aniline derivatives that have
electron-donating groups (Table 1, Entries 4 and 6) underwent
approximately complete conversion in a comparable time (3­
4.5 h), whereas p-methylbenzoic acid (Table 1, Entries 1 and 9)
and p-nitroaniline (Table 1, Entry 8) were found to react in a
relatively longer duration (6­8 h). The reaction of N-methyl-
aniline with different substituted benzoic acid was found to
afford the amides 3i­3k in high yields (Table 1, Entries 9­11).
In the case of synthesis of amides, the more nucleophilic N-
methylaniline (91%) compared to poorly nucleophilic aromatic
amines such as aniline (86%) gave the better yield (Table 1,
Entry 10 compared to Entry 2). The intriguing reactivity
observed with the variation of substituents in both acid and
aromatic amine is clearly suggestive of the dependence of the
reaction on acidity of benzoic acid derivatives and nucleophi-
licity of aromatic amines. As shown in Table 1, aliphatic amine
(Entries 12 and 16) and both aliphatic (Entry 14) and aromatic
acids (Entry 13) are suitable substrates for synthesis of the
corresponding amides 3l­3p. The successful transformation
of both aliphatic and aromatic thiocarboxylic acids to their
corresponding thioamides 3q and 3r was observed using the
same reaction conditions as carboxylic acids (Table 1, Entries
Our first attempts started with synthesis of 2,2¤-, 3,3¤-, and
,4¤-azopyridine (2a­2c) from oxidation of 2-, 3-, and 4-
4
aminopyridine (1a­1c) with sodium hypochlorite solution 6­
2
8
1
4% at 0 °C. We then applied this condition to the synthesis
of 2,2¤-azobenzothiazole (2d) and 5,5¤-dimethyl-3,3¤-azoisoxa-
zole (2e) from 2-aminobenzothiazole (1d) and 3-amino-5-
methylisoxazole (1e) (Scheme 1).
To test the usefulness of these heterocyclic aryl azo
compounds under Mitsunobu conditions for amidation of
carboxylic acids, we found that the 2,2¤- (2a) and 4,4¤-
azopyridines (2c) are nearly equally efficient reagents and
are more reactive than their 3,3¤-isomer 2b for amidation
of both aliphatic and aromatic amines with carboxylic acids.
In comparison, it was observed that heterocyclic azo com-
pounds based on benzothiazole 2d and isoxazole 2e are highly
selective reagents for amidation of only primary aromatic
amines.
Apart from the handling problems, a property that has
restricted the Mitsunobu reaction somewhat is the isolation and
purification of the desired product when contaminated by the
produced diethyl hydrazinedicarboxylate by-product from
DEAD. In addition, to the best of our knowledge, DEAD has
not been employed for amidation reactions.2
2,24
Although 2a
and 2c were found to be equally efficient and acceptable
alternatives for DEAD in the Mitsunobu reaction, since the
yield for synthesis of 2c is much higher than for 2a, this
compound was chosen as the reagent of choice for our study.
4
,4¤-Azopyridine (2c) can be simply purified by recrystalliza-
tion and is very stable with easy handling. It should be noted
that the 4,4¤-hydrazopyridine by-product is solid and usually
can be isolated from the reaction mixture by filtration. This
makes the workup much easier compared to DEAD. Addition-
ally, the resulting hydrazine by-product can also be recycled by
oxidation with iodosobenzene diacetate in DMSO at room
temperature to give the azo compound 2c,27 which can be
reused. In the amidation process, the reaction of benzoic acid
with aniline was chosen as a model reaction and carried
out with different ratios of RCO H/amine/2c/PPh . Of the
2
3
various stoichiometries, the ratio of 1.0/1.2/1.3/1.3 was the
best and gave a high yield of benzanilide (86%). In designing
our experiments we fixed the solvent as refluxing CH CN
3
(
Scheme 2).
With the optimized conditions in hand, a variety of
carboxylic acids and aromatic amines were converted into the

N. Iranpoor et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
925
Table 1. Synthesis of Amides under Condition of the Mitsunobu Reaction Using 2ca)
Entry
Acid
Amine
Productb)
Time/h
Yield/%c)
O
COOH
H N
2
N
H
1
2
3
6
77
H3C
H3C
3
a
O
COOH
H N
2
N
H
4.5
3.5
86
94
3
b
O
COOH
H N
2
N
H
O2N
O2N
3
c
OMe
O
O
H2N
COOH
4
5
6
7
8
9
0
N
H
4
91
82
89
85
70
88
91
94
87
OMe
OMe
3
d
e
COOH
COOH
COOH
COOH
H2N
N
H
OMe
4.5
4
3
O
H N
2
N
H
H C
CH3
3
3
f
Cl
O
H N
2
N
H
5.5
8
Cl
3
g
NO2
O
H N
2
N
H
NO2
CH3
3
h
O
COOH
H
N
N
6
H C
3
H C
3
3
i
O
H
N
COOH
N
1
CH3
CH3
CH3
5.5
3
3
j
O
COOH
H
N
N
11
O2N
O N
2
3
k
O
H
N
COOH
N
12
4.5
3
l
Continued on next page:

9
26
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
Continued:
Amidation and Mono-N-Benzylation of Amines
Entry
Acid
Amine
Productb)
Time/h
Yield/%c)
NH2
O
COOH
13
14
15
16
N
H
5
87
3
m
NH2
O
O
N
H
5
84
89
90
OH
3
n
O
COOH
COOH
NH
2
N
3.5
3.5
H
3
o
O
N
H
5 NH2
5
3
p
S
COSH
H2N
1
1
7
8
N
H
4
84
83
3
q
S
O
H N
2
N
4.5
H
SH
3
r
a) The molar ratio of the reactants for RCO2H/ArNHR/PPh3/azpy in refluxing CH3CN is 1.2/1.0/1.3/1.3.
b) The products were identified by their spectral data. c) Isolated yield.
1
7 and 18). Taking advantage of the versatility and stability of
(Table 2, Entry 8), lead to the desired product 3h with lower
yield due to the low nucleophilicity of amine. In addition to
this, gratifyingly, from the results depicted in Table 2, it can be
established that the amidation reaction that is performed with
two azo compounds 2d and 2e was successful only for
transformation of primary aromatic amines. Therefore, the use
of azo compounds 2d and 2e, more electron deficient than
azopyridines 2c, permitted highly selective preparation of
secondary aromatic amides 3a­3h, 3m, and 3n.
To investigate the selectivity of reactions of these azo
compounds 2d and 2e, we set up experiments using binary
mixtures of equimolar amounts of aniline and different
secondary aliphatic and aromatic amines with benzoic acid.
NMR and TLC analysis of the reaction mixture showed that
solely 3b was formed and no 3k, 3l, 3o, and 3p were observed
(Scheme 3).
azopyridines in the Mitsunobu reaction, we have synthesized
two new azo compounds 2d and 2e that have more than one
hetero atom in their aromatic ring and investigated their
abilities in amidation reaction. First of all, we carried out a
study of the proper conditions to carry out the amidation
reaction between acids and amines. The optimized conditions
such as solvent, ratio of reagents, and temperature were similar
to the previously optimized conditions for azopyridines. On the
basis of the optimized conditions, we probed their scope in the
amidation of various aryl-substituted acids by substituted
primary and secondary aliphatic and aromatic amines. Both
2
,2¤-azobenzothiazole (2d) and 5,5¤-dimethyl-3,3¤-azoisoxazole
(
2e) as well as 4,4¤-azopyridine (2c) could be employed
providing comparable isolated yields (Table 2).
As shown in Table 2, under refluxing CH CN, a variety of
3
primary aromatic amines were efficiently transformed into
amides 3a­3h, 3m, and 3n and the yields ranged from 66 to
The results of this study are also summarized in Table 3.
Crucially, treatment of a binary mixture of aniline and
benzylamine under the optimized amidation conditions gave
benzanilide (3b) as a single product, with none of the N-
benzylbenzamide (3o) detectable in either the crude or purified
products (76% yield for 2d and 80% for 2e, Table 3, Entry 2).
Reaction of benzoic acid with binary mixture including
primary aromatic amine such as aniline and secondary aliphatic
amines such as N-methyl-N-cyclohexylamine in the presence of
azo compounds 2d and 2e showed complete selectivity for the
aromatic amine over the secondary aliphatic amine, giving
benzanilide (3b) in a yield of 82% and 77%, in the case of 2d
and 2e respectively (Table 3, Entry 3). Reaction of the mixture
of aniline and N-methylaniline under the above reaction
9
3%. Both azo compounds 2d and 2e were applied for
thioamide formation from aliphatic and aromatic thiocar-
boxylic acids. (Table 2, Entries 11 and 12). The process of
amidation takes place as azopyridines, except that a longer
reaction time was required (Table 2, Entries 1 and 2 compared
to Table 1, Entries 1 and 2). The reaction tolerates electron-rich
and electron-poor substituents in both acid and amines. The
reaction of the aromatic and aliphatic carboxylic acids with
electron-rich and -poor substituents on the aromatic amine such
as ­OMe, ­Cl, and ­NO produced the corresponding amides
2
with acceptable yields (Table 2). However, the use of aniline
bearing an electron-withdrawing group such as the nitro

N. Iranpoor et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
927
Table 2. Conversion of Various Primary Aromatic Amines to Corresponding Amides Using 2d and 2e under Mitsunobu
a)
Conditions
2
d
2e
Yield/%c)
Entry
1
Acid
Amine
Productb)
Time/h
Yield/%c)
Time/h
O
COOH
H N
2
N
H
9
73
10.5
71
80
85
H C
3
H C
3
3
a
O
COOH
H N
2
N
2
3
7.5
5
75
88
8
5
H
3
b
O
COOH
H N
2
N
H
O2N
O N
2
3
c
OMe
O
O
H2N
COOH
4
5
6
7
N
H
7
7.5
5
93
77
84
87
70
8
9
90
79
89
90
66
OMe
OMe
3
3
d
e
COOH
COOH
COOH
H2N
N
H
OMe
O
H N
2
N
4.5
6.5
12
H
H C
CH3
3
3
f
Cl
O
H2N
N
H
6.5
11
Cl
3
g
NO2
O
O
S
H N
COOH
COOH
2
8
9
N
H
NO2
3
h
NH2
O
N
5
90
90
85
82
6
91
86
83
82
H
3
m
n
NH2
O
10
N
H
6.5
6
7.5
6.5
7.5
OH
3
S
COSH
H2N
11
N
H
3
q
O
H2N
12
N
H
6
SH
3
r
a) The molar ratio of the reactants for RCO2H/ArNH2/PPh3/azo in refluxing CH3CN is 1.2/1.0/1.3/1.3. b) The products
were identified by their spectral data. c) Isolated yield.

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Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
Amidation and Mono-N-Benzylation of Amines
O
NH2
O
HN
Ph
2
d or 2e, PPh3
R
RNHR'
+
+
N
Ph
PhCO H, CH CN, reflux
2
3
R'
3
b
100:0
3k,l,o,p
R = PhCH ,n-Octyl, Cyclohexyl, Ph
2
R' = H, Me
Scheme 3.
Table 3. Selective Conversion of Various Amines with
Benzoic Acid in Binary Mixtures to Corresponding
Amides Using 2d and 2e under Mitsunobu Conditions
Table 4. Azo Reagent Optimization for N-Benzylation of
Aniline
a)
H
2
d
2e
NH2
N
Conversion
HO
Azo, PPh3
Entry Binary mixture
Time Yield Time Yield
b)
+
/%
CH CN, reflux
3
c)
c)
/
h
/%
/h /%
8.5 82
80
n
PhNH2
1
o
o
o
o
4
a
3b 100
CH3(CH2)6CH2NH2 3p 0
8.5 79
7.5 76
n
n
n
Azo
Yield of 4a/%a)
Time/h
PhNH2
3b 100
3o 0
3b 100
3l 0
3b 100
3k 0
2
3
4
8
2
c
80
71
68
7
11
12
PhCH2NH2
PhNH2
Cyclohex-NH-Me
PhNH2
2
d
8
7
82
86
8.5 77
7.5 83
2
e
a) Isolated yield.
PhNHMe
a) The molar ratio of Ph3P/2d or 2e/binary mixture/acid is
.3/1.3/1.2/1.0. b) Analysis by TLC. c) Isolated yield.
2c (1.3 equiv),
PPh (1.3 equiv)
1
ArNHR1
2
3
ArNR R2
1
+
R OH
CH CN, reflux
3
conditions in acetonitrile resulted in a complete conversion,
yielding 3b as a single product selectively (Table 3, Entry 4).
Despite versatility and significant improvements in the
Mitsunobu reaction, attempts to apply DEAD and its derivatives
to the alkylation of amines have not been satisfied by the low
acidity of amines. In the case of amines, the yields are higher
1.2 equiv
1.0 equiv
1
R = H, CH , COCH
3
3
2
R = ArCH
2
Scheme 4.
with lower pK of the amine component and due to the low
a
acidity; aliphatic amines are usually resistant toward N-alkyla-
tion. According to our knowledge, there are very few examples
in the literature where the Mitsunobu reaction has been used to
The obtained results are summarized in Table 5. As these
data indicate, N-alkylation of disparate anilines with benzyl
alcohols bearing electron-donating and electron-withdrawing
substituents at the aromatic ring proceeded to give benzyl-
anilines derivatives in good to excellent yields.
29
form alkylated amines. However, N­H acidic compounds,
such as sulfonamides,30 cyclic imides, and amides can be N-
alkylated satisfactorily under Mitsunobu reaction conditions.
To extend the applicability of our methodology and find out
the limitations encounter on using these novel azo compounds
31
32
Anilines and benzyl alcohols substituted with an ­OMe
group resulted in a nearly complete conversion during their
reactions, and the products 4h and 4i were obtained in 87% and
92% yields. Other primary, and secondary aliphatic and also
secondary benzylic alcohols, such as 1-octanol, 2-octanol, and
1-phenylethanol were not applicable to this reaction. In the case
of the less reactive (Table 5, Entries 5, 6, 11, and 14) and more
hindered ortho-substituted alcohols (Table 5, Entries 3 and 6),
the reaction did reach completion under the reaction conditions.
N-alkylation of secondary aromatic amine was also examined.
Reactions of N-methylaniline with benzyl alcohol proceeded
to give its corresponding tertiary amine 4o in moderate yield
(77%, Table 5, Entry 15). The reaction of acetanilide with
benzyl alcohol resulted in the formation of N-benzylacetanilide
in good yield (84%, Table 5, Entry 16). We briefly also
examined the reaction of imides and sulfonamides with benzyl
alcohol under these condition and we found that this method
2
c, 2d, and 2e, we sought conditions for performing N-
alkylation of various amines. As expected, our attempts to
alkylate aliphatic amines (e.g., n-butylamine) under the afore-
mentioned conditions were unsuccessful. The reason for this
observation is due to the fact that the Mitsunobu reactions
generally proceed best with acidic nucleophiles.33 However N-
alkylation of primary aromatic amines with benzyl alcohols
in the presence of 2c, 2d, and 2e proceeded to give the
corresponding N-benzylamines in good yields. The azo reagent
optimization when aniline and benzyl alcohol were used as the
starting material clearly indicated that 2c is a more suitable azo
reagent in terms of yield and reaction time (Table 4).
We found that this reaction has maximal yield when we use
the molar ratios of 1.0/1.2/1.3/1.3 for ROH/ArNHR/2c/PPh3
in refluxing CH CN (Scheme 4).
3

N. Iranpoor et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
929
Table 5. Benzylamines Synthesized via Mitsunobu Reaction Using azpy 2ca)
Entry
Alcohol
Amine
Productb)
Time/h
Yield/%c)
H
N
NH2
HO
1
2
7
80
4
4
a
OMe
H
N
NH2
HO
6
83
OMe
b
c
H
NH2
NH2
NH2
HO
MeO
N
3
4
6.5
7.5
81
75
OMe
4
HO
H
N
OMe
NO2
OMe
4
4
d
H
N
HO
5
6
7
8
8.5
9
68
64
75
87
NO2
e
f
H
NH2
HO
O2N
N
NO2
4
Cl
H
NH2
HO
N
7.5
6
Cl
4
g
H
N
NH2
HO
MeO
MeO
MeO
MeO
Cl
MeO
4
h
i
OMe
NH2
H
HO
N
9
0
5.5
®
7
92
®
73
75
OMe
MeO
4
H
N
NH2
1
HO
MeO
4
j
NO2
NH2
H
HO
N
11
NO2
MeO
4
k
H
N
NH2
HO
12
7.5
Cl
4
l
Continued on next page:

9
30
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
Continued:
Amidation and Mono-N-Benzylation of Amines
Entry
Alcohol
Amine
Productb)
Time/h
Yield/%c)
OMe
NO2
NH2
H
N
HO
HO
1
3
6.5
78
Cl
Cl
OMe
Cl
Cl
4
m
NH2
H
N
1
1
4
5
8
6
74
77
NO2
4
n
o
H
N
N
HO
CH3
4
H
N
CH3
HO
HO
1
1
6
7
N
CH3
6.5
84
90
O
O
O
4
p
O
NH
N
6
O
4
O
q
NO2
NO2
HO
HO
1
1
8
9
SO NHCH Ph
6
6
81
5
2
2
SO NH
2
2
4
r
H C
SO NH2
H C
SO NHCH Ph
2 2
3
2
3
a) The molar ratio of the reactants for ROH/ArNHR/azpy/PPh3 in refluxing CH3CN is 1/1.2/1.2/1.2. b) The
products were identified by their spectral data. c) Isolated yield.
can also be used for N-alkylation of imides and benzene
sulfonamides having electron-withdrawing substitutents. In the
case of phthalimide, the desired monoalkylated product, N-
benzylphthalimide (4q), was isolated in excellent yield (90%,
Table 5, Entry 17). 2-Nitrobenzenesulfonamide also took part
in the reaction to afford the corresponding N-benzyl-2-
nitrobenzenesulfonamide (4r) in good yield, while 4-methyl-
benzenesulfonamide remained almost intact (Table 5, Entries
product was obtained just in low yield of 10% as well as the
mono-alkylated product (69%) indicating the high selectivity
of the method for mono-alkylation reaction. A plausible
mechanism that might explain these results is depicted in
Scheme 5. Isolation of Ph PO and hydrazopyridine supports
3
the suggested mechanism.
Conclusion
1
8 and 19). Aliphatic amines were also tested for N-alkylation
In summary, we have developed novel azo reagents 2c for
the efficient and robust amidation of carboxylic acids with
different aromatic and aliphatic amines and 2d and 2e for the
highly selective amidation of only primary aromatic amines.
Selective N-benzylation of primary and secondary aromatic
amines can also be achieved with all three heteroaryl azo
compounds 2c­2e using a Mitsunobu protocol. Apart from
easy synthesis, stability and ease of handling of these azo
compounds instead of DEAD, a clear advantage gained is
that the side product hydrazine can be removed easily and
reoxidized to the original azo. The excellent selectivity
obtained in amidation reaction based on the different reactivity
of these azo compounds and also their uses for the selective
mono-N-benzylation of amines can be regarded as useful
achievements in the Mitsunobu reaction.
but our attempts at their alkylation under the aforementioned
conditions were unsuccessful. This observation is conformable
to the prior studies on N-alkylation of amines under condition
of Mitsunobu reaction.2
9a,29b
To gain further insight about the reactivity of azo pyridine
c, an experiment was performed under intentionally harsh
2
conditions. A mixture of primary aliphatic amine such as n-
butylamine and n-butyllithium was treated with benzyl alcohol,
in the presence of azpy 2c and PPh and the reaction was
allowed to proceed overnight in refluxing acetonitrile in order
to purposely perform the alkylation of inactive n-butylamine.
Regretfully, no product was detected. When the reaction of
aniline with benzyl alcohol was performed using an excess
amount of benzyl alcohol (2.0 equiv) for 10 h, the di-alkylated
3

N. Iranpoor et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
931
N
N N
PPh3
N
N
N N
PPh3
N
N
N N
PPh3
N
2c
O
HXCAr
R'OH
X = O, S
H
H
N
N N
N
N
N N
N
Ph P
Ph P
3
3
X
O
RNHR'
R'
ArNHR
O
Ar
R = H, Alkyl
R' = ArCH
2
R =Alkyl, Aryl
R'=H, Alkyl
-
OPPh3
-
XPPh3
ArCONRR'+ hydrazopyridine
hydrazopyridine + ArNRR'
PhI(OAc)2
2c
Scheme 5.
solution under vacuum, azopyridine 2a was precipitated as orange
crystals (127 mg, 69%).
Experimental
Solvents were dried and purified by standard procedures.
Melting points were determined in open capillary tubes in a Buchi
Typical Procedure for the Conversion of Benzoic Acid to
Benzanilide. To a stirred solution of 4,4¤-azopyridine (1.3 mmol,
0.239 g) and PPh3 (1.3 mmol, 0.338 g) in 3 mL of CH3CN was
added benzoic acid (1 mmol, 0.12 g) and aniline (1.2 mmol,
0.11 mL) successively. The reaction mixture was refluxed and
completion of the reaction was monitored by TLC for the
consumption of benzoic acid. After completion of the reaction,
the reaction mixture was filtered to remove the precipitated
hydrazopyridine. The residue was washed with 4% aq. HCl to
remove the excess aniline and dried with anhydrous Na2SO4.
Evaporation of the solvent followed by column chromatography of
the crude mixture on silica gel using n-hexane and ethyl acetate
(3:1) as eluent gave benzanilide (3b) in good yield (0.17 g, 86%).
5
30 circulating oil apparatus and are not corrected. FT-IR spectra
were run on a Shimadzu FTIR-8300 spectrophotometer. NMR
1
spectra were recorded on a Bruker Avance DPX-250 ( H NMR
2
50 MHz, 13C NMR 62.9 MHz) spectrometer in CDCl3 or DMSO-
d6 solvents using TMS as an internal standard.
Determination of the purity of the products and the reaction
monitoring were carried out on silica gel 254 analytical sheets or
by GLC on a Shimadzu model GC-10A instrument. Column
chromatography was carried out on silica gel 60 Merck (230­270).
All compounds had been reported previously, and their identities
were confirmed by comparison of their physical and spectroscopic
data with those of known compounds. Characterization data for the
compounds 3a­3d, 3f­3h, 3j, 3k, 3o, 3p, 4a­4e, 4g, 4h, 4l, 4o, and
34a,34e
¹1
Mp 163 °C, mp 160­161 °C, Lit;
IR (neat, cm ): 3344, 3050,
1
2918, 1654, 1597. H NMR (250 MHz, CDCl3): ¤ 8.08­7.15 (m,
11H). 13C NMR (62.9 MHz, CDCl3): ¤ 165.8, 137.9, 133.6, 131.8,
128.8, 128.4, 127.0, 124.61, 120.3. Anal. Calcd for C13H11NO: C,
79.16; H, 5.62; N, 7.10%. Found: C, 79.10; H, 5.70; N, 7.13%.
4-Methyl-N-phenylbenzamide (3a): Mp 147 °C, mp 145 °C,
Lit.34h IR (KBr, cm ): 3345, 3061, 1650. 1H NMR (250 MHz,
CDCl3): ¤ 7.90 (br s, 1H, NH), 7.68 (d, 2H, J = 8.0 Hz), 7.59 (d,
2H, J = 7.6 Hz), 7.42 (t, 2H, J = 7.8 Hz), 7.25 (d, 2H, J = 8.2 Hz),
7.23 (t, 1H, J = 7.4 Hz), 2.38 (s, 3H). 13C NMR (62.9 MHz,
CDCl3): ¤ 167.2, 142.5, 138.3, 137.8, 131.6, 129.5, 129.1, 128.4,
124.6, 119.8, 21.3. Anal. Calcd for C14H13NO: C, 79.59; H, 6.20;
N, 6.63%. Found: C, 79.52; H, 6.25; N, 6.62%.
4
q are shown below.
General Procedure for Synthesis of Azo Compounds. Azo
compounds 2a­2e were prepared by oxidative coupling of amino-
pyridine by sodium hypochlorite solution. A 100-mL aliquot of a
cold solution of aminopyridine (2.5 g) in water (aminobenzothia-
zole and aminooxazole were dissolved in THF) was added
dropwise to 200 mL of a 6­14% NaOCl solution. The mixture
was stirred at 0 °C as a precipitate formed. Filtration was
performed a few minutes after the end of addition, and participates
were collected and were used in our reactions without any
purification.
¹1
Oxidation of Hydrazopyridine to Azopyridine by Iodoben-
zene Diacetate PhI(OAc)2. Iodosobenzene diacetate (0.322 g,
4-Nitro-N-phenylbenzamide (3c): Mp 211­213 °C, mp 211­
212 °C, Lit.3 IR (KBr, cm ): 3344, 3059, 1646. H NMR (250
MHz, DMSO-d6): ¤ 10.54 (br s, 1H, NH), 8.36 (d, 2H, J = 8.8 Hz),
8.16 (d, 2H, J = 8.8 Hz), 7.76 (d, 2H, J = 8.3 Hz), 7.36 (m, 2H),
7.15­7.10 (m, 1H). 13C NMR (62.9 MHz, DMSO-d6): ¤ 164.2,
157.5, 134.1, 133.8, 129.2, 128.7, 124.1, 123.5, 120.4. Anal. Calcd
for C13H10N2O3: C, 64.46; H, 4.16; N, 11.56%. Found: C, 64.51;
H, 4.15; N, 11.50%.
4i
¹1
1
1
.0 mmol) was added in one portion to a stirred solution of
pyridinehydrazine (0.186 g, 1.0 mmol) in 7 mL of DMSO and the
reaction mixture was stirred at room temperature for 6 h. H2O
(
20 mL) was then added and the reaction solution was extracted
with EtOAc (3 © 20 mL). The organic extracts were combined
together and dried over anhydrous MgSO4. Upon concentrating the

9
32
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
Amidation and Mono-N-Benzylation of Amines
N-(4-Methoxyphenyl)benzamide (3d): Mp 154 °C, mp 156­
in 3 mL of acetonitrile, was added benzyl alcohol (1 mmol,
0.1 mL). Aniline (1.2 mmol, 0.11 mL) was then added to the
reaction mixture. The reaction mixture was refluxed for 7 h. The
reaction mixture was then filtered to remove some of the produced
hydrazopyridine. The solvent was then evaporated and the residue
was chromatographed on a silica gel column using n-hexane
and ethyl acetate (4:1) as eluent. N-Phenylbenzylamine (4a) was
57 °C, Lit.3 IR (neat, cm¹1): 3335, 3054, 1645. H NMR
4c
1
1
(
250 MHz, CDCl3): ¤ 7.77 (d, 2H, J = 8.1 Hz), 7.64 (br s, 1H,
NH), 7.61­7.39 (m, 5H), 6.78 (d, 2H, J = 8.5 Hz), 3.85 (s, 3H).
C NMR (62.9 MHz, CDCl3): ¤ 165.7, 155.9, 137.1, 132.3, 131.2,
28.9, 127.5, 122.0, 121.7, 114.9, 114.2, 55.4. Anal. Calcd for
C14H13NO2: C, 73.99; H, 5.77; N, 6.16%. Found: C, 73.97; H,
13
1
34a,34k
5
1
.80; N, 6.13%.
obtained in 80% yield (0.146 g). Mp 37 °C, Lit.,
mp 37.5 °C;
¹1
1
N-(2-Methylphenyl)benzamide (3f): Mp 144 °C, mp 142­
IR (KBr, cm ): 3403, 1325. H NMR (250 MHz, CDCl3): ¤ 7.43­
7.22 (complex, 8H), 6.79­6.68 (complex, 3H), 4.38 (s, 2H).
43 °C, Lit.3 IR (KBr, cm ): 3325, 3050, 1648. H NMR (250
4d
¹1
1
13
MHz, CDCl3): ¤ 7.81­7.78 (m, 3H), 7.65 (br s, 1H, NH), 7.47­
C NMR (62.9 MHz, CDCl3): ¤ 148.2, 139.5, 129.3, 128.4, 127.6,
7
.40 (m, 3H), 7.17­7.13 (m, 2H), 7.06­7.03 (m, 1H), 2.24 (s, 3H).
C NMR (62.9 MHz, CDCl3): ¤ 165.4, 135.8, 135.1, 134.0, 131.8,
30.6, 129.1, 128.8, 127.1, 126.9, 125.4, 123.2, 122.5, 17.8. Anal.
127.3, 117.6, 112.9, 48.4. Anal. Calcd for C13H13N: C, 85.21; H,
1
3
7.15; N, 7.64%. Found: C, 85.16; H, 7.20; N, 7.64%.
4-Methoxy-N-phenylbenzylamine (4b):3
4j
1H NMR (250
1
Calcd for C14H13NO: C, 79.59; H, 6.20; N, 6.63%. Found: C,
MHz, CDCl3): ¤ 7.31 (d, 2H, J = 7.5 Hz), 7.13­6.51 (m, 7H), 4.39
(s, 2H), 3.91 (br s, 1H, NH), 3.74 (s, 3H). 13C NMR (62.9 MHz,
CDCl3): ¤ 157.8, 149.1, 131.8, 129.9, 129.6, 128.3, 118.6, 115.5,
114.1, 113.0, 56.1, 49.7. Anal. Calcd for C14H15NO: C, 78.84; H,
7
9.60; H, 6.21; N, 6.60%.
N-(4-Chlorophenyl)benzamide (3g): Mp 187 °C, mp 188­
4e
¹1
1
1
90 °C, Lit.3 IR (KBr, cm ): 3341, 3052, 1652. H NMR (250
MHz, CDCl3): ¤ 7.76 (d, 2H, J = 7.0 Hz), 7.70 (s, 1H), 7.65­7.52
7.09; N, 6.57%. Found: C, 78.81; H, 7.07; N, 6.59%.
2-Methoxy-N-phenylbenzylamine (4c):
MHz, CDCl3): ¤ 7.24­7.02 (m, 4H), 6.79­6.53 (m, 5H), 4.40 (s,
2H), 4.05 (br s, 1H, NH), 3.80 (s, 3H). 13C NMR (62.9 MHz,
CDCl3): ¤ 159.1, 146.7, 130.1, 129.6, 128.7, 127.9, 121.4, 118.5,
112.9, 110.8, 57.3, 45.4. Anal. Calcd for C14H15NO: C, 78.84; H,
1
3
34k
1H NMR (250
(
¤
m, 5H), 7.44 (d, 2H, J = 8.7 Hz). C NMR (62.9 MHz, CDCl3):
163.9, 137.3, 132.2, 128.9, 127.6, 126.7, 126.1, 121.6, 120.8.
Anal. Calcd for C13H10ClNO: C, 67.39; H, 4.35; N, 6.05%. Found:
C, 67.44; H, 4.28; N, 6.06%.
N-(4-Nitrophenyl)benzamide (3h):
Mp 197 °C, mp 198­
4f
¹1
1
1
99 °C, Lit.3 IR (KBr, cm ): 3347, 3044, 1655. H NMR (250
7.09; N, 6.57%. Found: C, 78.85; H, 7.09; N, 6.60%.
3-Methoxy-N-phenylbenzylamine (4d):3
4j
1H NMR (250
MHz, DMSO-d6): ¤ 9.95 (br s, 1H, NH), 8.18­7.83 (d, 2H, J = 7.2
1
3
Hz), 7.76­7.69 (m, 3H), 7.55­7.39 (m, 4H). C NMR (62.9 MHz,
DMSO-d6): ¤ 164.0, 143.1, 141.4, 131.6, 129.2, 128.6, 128.1,
MHz, CDCl3): ¤ 7.29­6.72 (m, 9H), 4.37 (s, 2H), 4.11 (br s, 1H,
NH), 3.84 (s, 3H). 13C NMR (62.9 MHz, CDCl3): ¤ 159.7, 146.8,
140.4, 130.2, 129.6, 129.1, 118.8, 118.0, 112.9, 112.4, 112.0, 56.7,
49.3. Anal. Calcd for C14H15NO: C, 78.84; H, 7.09; N, 6.57%.
1
1
23.3, 120.0. Anal. Calcd for C13H10N2O3: C, 64.46; H, 4.16; N,
1.56%. Found: C, 64.50; H, 4.14; N, 11.53%.
N-Methyl-N-phenylbenzamide (3j): Mp 104­106 °C, mp
Found: C, 78.88; H, 7.12; N, 6.56%.
03­104 °C, Lit.34g IR (KBr, cm ): 3049, 1642. H NMR (250
¹1
1
4-Nitro-N-phenylbenzylamine (4e):
34k
IR (neat, cm¹1): 3412.
1
1
MHz, CDCl3): ¤ 7.65 (d, 2H, J = 7.1 Hz), 7.47­7.14 (m, 3H),
H NMR (250 MHz, CDCl3): ¤ 8.18­8.13 (m, 2H), 7.71­7.56
1
3
6
1
.93­6.71 (m, 5H), 3.52 (s, 3H). C NMR (62.9 MHz, CDCl3): ¤
(m, 2H), 7.37­7.23 (m, 2H), 6.84­6.68 (m, 3H), 4.38 (s, 2H), 4.11
(br s, 1H, NH). 13C NMR (62.9 MHz, CDCl3): ¤ 146.4, 144.9,
143.7, 130.5, 128.4, 124.5, 117.7, 113.5, 48.9. Anal. Calcd for
C13H12N2O2: C, 68.41; H, 5.30; N, 12.27%. Found: C, 68.44; H,
5.36; N, 12.24%.
68.3, 142.7, 136.4, 129.1, 129.0, 128.7, 127.5, 126.7, 126.0, 39.6.
Anal. Calcd for C14H13NO: C, 79.59; H, 6.20; N, 6.63%. Found:
C, 79.54; H, 6.23; N, 6.59%.
N-Methyl-4-nitro-N-phenylbenzamide (3k): Mp 109­111,
3
4h
IR (KBr, cm¹1): 3055, 1646. 1H NMR
4-Chloro-N-phenylbenzylamine (4g):34l 1H NMR (250 MHz,
CDCl3): ¤ 7.12­6.61 (m, 9H), 4.29 (s, 2H), 3.92 (br s, 1H, NH).
mp 106­107 °C, Lit.
(
(
250 MHz, CDCl3): ¤ 8.33­8.01 (m, 4H), 6.82­6.63 (m, 5H), 3.46
s, 3H). 13C NMR (62.9 MHz, CDCl3): ¤ 165.7, 150.6, 144.3,
13
C NMR (62.9 MHz, CDCl3): ¤ 148.6, 139.1, 133.4, 129.8, 128.3,
1
41.3, 132.6, 130.8, 130.2, 128.7, 124.5, 37.8. Anal. Calcd for
128.0, 119.2, 114.5, 48.3. Anal. Calcd for C13H12ClN: C, 71.72; H,
C14H12N2O3: C, 65.62; H, 4.72; N, 10.93%. Found: C, 65.62; H,
5.56; N, 6.43%. Found: C, 71.68; H, 5.60; N, 6.40%.
N-(4-Methoxyphenyl)benzylamine (4h):3
4j
1H NMR (250
4
.69; N, 10.98%.
N-Benzylbenzamide (3o): Mp 104­106 °C, mp 103­104 °C,
MHz, CDCl3): ¤ 7.17 (d, 2H, J = 7.3 Hz), 7.08­7.06 (m, 3H), 6.48
(d, 2H, J = 8.0 Hz), 6.34 (d, 2H, J = 7.9 Hz), 4.39 (s, 2H), 4.11
(br s, 1H, NH), 3.76 (s, 3H). 13C NMR (62.9 MHz, CDCl3): ¤
153.5, 141.2, 140.7, 127.8, 127.6, 127.0, 117.1, 115.3, 50.1. Anal.
Calcd for C14H15NO: C, 78.84; H, 7.09; N, 6.57%. Found: C,
78.83; H, 7.11; N, 6.52%.
Lit.34b IR (KBr, cm ): 3318, 1634. H NMR (250 MHz, CDCl3): ¤
7
4
1
¹1
1
.70 (d, 2H, J = 8.4 Hz), 7.40­7.21 (m, 8H), 6.53 (br s, 1H, NH),
1
3
.54 (d, 2H, J = 5.7 Hz). C NMR (62.9 MHz, CDCl3): ¤ 167.4,
38.2, 134.4, 131.5, 128.8, 128.6, 127.9, 127.6, 127.0, 44.1. Anal.
Calcd for C14H13NO: C, 79.59; H, 6.20; N, 6.63%. Found: C,
9.65; H, 6.21; N, 6.60%.
N-Octylbenzamide (3p): IR (neat, cm¹1): 3313, 3041, 1635.
H NMR (250 MHz, CDCl3): ¤ 7.68 (d, 2H, J = 8.2 Hz), 7.41­7.30
m, 3H), 6.16 (br s, 1H, NH), 3.36 (t, 2H, J = 8.3 Hz), 1.59­1.39
m, 2H), 1.25­1.09 (m, 10H), 0.84 (t, 3H, J = 6.9 Hz). 13C NMR
62.9 MHz, CDCl3): ¤ 167.3, 134.9, 131.8, 131.24, 128.5, 127.9,
26.8, 40.1, 31.8, 29.7, 29.3, 29.2, 27.0, 22.6, 14.1. Anal. Calcd
for C15H23NO: C, 77.21; H, 9.93; N, 6.00%. Found: C, 77.19; H,
7
N-(4-Chlorophenyl)benzylamine (4l):34j 1H NMR (250 MHz,
CDCl3): ¤ 7.14 (d, 2H, J = 7.2 Hz), 7.05­7.02 (m, 5H), 6.44 (d,
1
13
2H, J = 7.1 Hz), 4.37 (s, 2H), 4.08 (br s, 1H, NH). C NMR (62.9
(
(
(
MHz, CDCl3): ¤ 150.2, 141.4, 128.7, 127.3, 127.0, 125.3, 119.5,
49.2. Anal. Calcd for C13H12ClN: C, 71.72; H, 5.56; N, 6.43%.
Found: C, 71.76; H, 5.51; N, 6.45%.
3
4m
IR (neat, cm¹1):
1
N-Methyl-N-phenylbenzylamine (4o):
1
1349. H NMR (250 MHz, CDCl3): ¤ 7.27­7.02 (m, 7H), 6.86­
6.71 (m, 3H), 4.33 (s, 2H), 3.11 (s, 3H). 13C NMR (62.9 MHz,
CDCl3): ¤ 149.4, 135.9, 129.7, 128.7, 126.0, 125.2, 117.4, 112.6,
59.3, 38.1. Anal. Calcd for C14H15N: C, 85.24; H, 7.66; N, 7.10%.
Found: C, 85.19; H, 7.65; N, 7.16%.
9
.89; N, 6.05%.
Typical Procedure for the Conversion of Aniline to N-
Phenylbenzylamine. To a flask containing a stirred mixture of
,4¤-azopyridine (1.3 mmol, 0.239 g) and PPh3 (1.3 mmol, 0.338 g)
4

N. Iranpoor et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 8 (2010)
933
N-Benzylphthalimide (4q): 1H NMR (250 MHz, CDCl3): ¤
Chem., Int. Ed. 2004, 43, 590. i) J.-L. Liang, X.-Q. Yu, C.-M. Che,
Chem. Commun. 2002, 124. j) S. I. Lee, S. U. Son, Y. K. Chung,
Chem. Commun. 2002, 1310.
10 F. Y. Rachinskii, T. G. Potapenko, O. D. Shapilov, V. T.
Osipyan, A. A. Krupenina, Zh. Prikl. Khim. (S.-Peterburg, Russ.
Fed.) 1968, 41, 1072.
11 a) M. B. Smith, J. March, March’s Advanced Organic
Chemistry, 6th ed., Wiley, New Jersy, 2007, p. 555. b) K. Mohri,
K. Suzuki, M. Usui, K. Isobe, Y. Tsuda, Chem. Pharm. Bull. 1995,
43, 159.
7
5
1
.75­7.72 (m, AA¤, 2H), 7.61­7.58 (m, XX¤, 2H), 7.36­7.16 (m,
H), 4.75 (s, 2H). 1 C NMR (62.9 MHz, CDCl3): ¤ 168.1, 136.4,
34.0, 132.1, 128.6, 127.6, 127.0, 123.3, 41.6. Anal. Calcd for
3
C15H11NO2: C, 75.94; H, 4.67; N, 5.90%. Found: C, 75.90; H,
4
.68; N, 5.92%.
N-Benzyl-2-nitrobenzenesulfonamide (4r):34n 1H NMR (250
MHz, CDCl3): ¤ 8.03 (dd, 1H, J = 7.8, 1.8 Hz), 7.83 (dd, 1H,
J = 7.9, 1.8 Hz), 7.75­7.60 (m, 2H), 7.25­7.01 (m, 5H), 5.66 (br s,
1
3
1
H, NH), 4.30 (s, 2H). C NMR (62.9 MHz, CDCl3): ¤ 147.5,
1
35.9, 134.2, 133.1, 132.6, 130.7, 129.1, 128.3, 127.7, 124.8, 47.6.
12 a) M. H. S. A. Hamid, J. M. J. Williams, Chem. Commun.
2007, 725. b) Y. Watanabe, Y. Morisaki, T. Kondo, T. Mitsudo, J.
Org. Chem. 1996, 61, 4214. c) C.-H. Jun, D.-C. Hwang, S.-J. Na,
Chem. Commun. 1998, 1405. d) G. Bitsi, E. Schleiffer, F. Antoni,
G. Jenner, J. Organomet. Chem. 1989, 373, 343.
13 a) R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit, N.
Tongpenyai, J. Chem. Soc., Chem. Commun. 1981, 611. b) T.
Rische, B. Kitsos-Rzychon, P. Eilbracht, Tetrahedron 1998, 54,
2723.
Anal. Calcd for C13H12N2O4S: C, 53.42; H, 4.14; N, 9.58; S,
1
0.97%. Found: C, 53.37; H, 4.16; N, 9.53; S, 11.01%.
2
8
4
,4¤-Azopyridine (2c):
Mp 106­107 °C (lit. Mp 107­
¹1
1
1
¤
08 °C). IR (KBr, cm ): 3028, 1585. H NMR (250 MHz, CDCl3):
7.7 (4H, m, AA¤XX¤), 8.7 (4H, m, AA¤XX¤). 13C NMR (62.9
MHz, CDCl3): ¤ 116.3, 151.5, 156.5. MS (m/z %): 184 (11.5), 106
14.6), 92 (6.9), 78 (39.0). Anal. Calcd for C10H8N4: C, 65.21; H,
(
4
.38; N, 30.42%. Found: C, 65.19; H, 4.43; N, 30.39%.
1
4
K. Fujita, Z. Li, N. Ozeki, R. Yamaguchi, Tetrahedron Lett.
The authors are grateful for the partial financial support from
2003, 44, 2687.
the Shiraz university research council.
15 M. S. R. Murty, B. Jyothirmai, P. R. Krishna, J. S. Yadav,
Synth. Commun. 2003, 33, 2483.
1
6
M. Kimura, M. Futamata, K. Shibata, Y. Tamaru, Chem.
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