The application of N,N′dibromo-N,N′-1,2-ethanediyl bis(P-toluenesulfonamide) as a powerful reagent for conversion of carboxylic acids into esters and amides with triphenylphosphine

Article abstract of DOI:10.1080/10426500490466292

In the presence of equivalent amounts of triphenylphenylphosphine and N,N′-dibromo-N,N′-1,2-ethanediylbis(p-toluenesulphonamide) ester and amide compounds can be generated in high yields from the corresponding carboxylic acid and alcohols or amines.

Full text of DOI:10.1080/10426500490466292

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Phosphorus, Sulfur, and Silicon and the Related
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THE APPLICATION OF N,N′DIBROMO-N,N′-1,2-
ETHANEDIYL BIS(P-TOLUENESULFONAMIDE) AS
A POWERFUL REAGENT FOR CONVERSION OF
CARBOXYLIC ACIDS INTO ESTERS AND AMIDES WITH
TRIPHENYLPHOSPHINE
Ardeshir Khazaei a , Shadpour Mallakpour b , Mohammad Ali Zolfigol a , Ramin Ghorbani-
Vaghei a & Eskandar Kolvari a
a Department of Chemistry, Faculty of Science , Hamedan, IR, Iran
b College of Chemistry, Isfahan University of Technolegy , Isfahan, IR, Iran
Published online: 16 Aug 2010.
To cite this article: Ardeshir Khazaei , Shadpour Mallakpour , Mohammad Ali Zolfigol , Ramin Ghorbani-Vaghei & Eskandar
Kolvari (2004) THE APPLICATION OF N,N′DIBROMO-N,N′-1,2-ETHANEDIYL BIS(P-TOLUENESULFONAMIDE) AS A POWERFUL
REAGENT FOR CONVERSION OF CARBOXYLIC ACIDS INTO ESTERS AND AMIDES WITH TRIPHENYLPHOSPHINE, Phosphorus, Sulfur,
and Silicon and the Related Elements, 179:9, 1715-1721, DOI: 10.1080/10426500490466292
To link to this article: http://dx.doi.org/10.1080/10426500490466292
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Phosphorus, Sulfur, and Silicon, 179:1715–1721, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490466292
THE APPLICATION OF
N,N ꢀDIBROMO-N,N ꢀ-1,2-ETHANEDIYL
BIS( P-TOLUENESULFONAMIDE) AS A POWERFUL
REAGENT FOR CONVERSION OF CARBOXYLIC
ACIDS INTO ESTERS AND AMIDES WITH
TRIPHENYLPHOSPHINE
Ardeshir Khazaei,a Shadpour Mallakpour,b Mohammad Ali
Zolfigol,a Ramin Ghorbani-Vaghei,a and Eskandar Kolvaria
Department of Chemistry, Faculty of Science, Bu-Ali Sina
University, Hamedan, IR, Iran;a and College of Chemistry,
Isfahan University of Technolegy, Isfahan, IR, Iranb
(Received November 25, 2003; accepted December 30, 2003)
In the presence of equivalent amounts of triphenylphenylphosphine
and N,Nꢁ-dibromo-N,Nꢁ-1,2-ethanediylbis(p-toluenesulphonamide) es-
ter and amide compounds can be generated in high yields from the
corresponding carboxylic acid and alcohols or amines.
Keywords: Acylation; alcohol; amide; amine; BNBTS; ester; Ph3P
The conversion of carboxylic acids to esters and amides are commonly
encountered reactions in organic chemistry.
A large number of ester-protecting groups have been described in
the literature.1 Although a variety of conditions for ester formation
have been developed,2 they are not always satisfactory in yield and/or
simplicity of operation. Most require either the presence of strong acids,
bases, or other catalysts, or the application of heat. Simple processes
that allow esterification under mild conditions are very desirable. These
procedures are of considerable interest, especially in the construction
of many peptides, macrolides,3 and natural products.
Several methods were reported for activation of carboxylic acids
and their conversion to esters and other derivatives. The most common
We are grateful to the Research Council of Isfahan University of Technology and the
Research Council of Bu-Ali Sina University for the financial support.
Address correspondence to Ardeshir Khazaei, Department of Chemistry, Faculty
of Science, Bu-Ali Sina University, P.O. Box: 65174-4119, Hamedan, Iran. E-mail:
khazaei 1326@yahoo.com
1715

1716
A. Khazaei et al.
FIGURE 1
are carbodiimides,4 N-acyl derivatives of imidazole,5 acylcarbonates,2f,6
(1,1ꢁ-carbonyldioxy)dibenzotriazoles,7 chlorotrimethylsilane,2a,8 seve-
ral oganophosphorus reagents,9 sulfonylchlorides,2e sulfuryl chloro-
floride,10 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline (EEDQ),11
pyridine-2-thiol esters,12 and alkylchloroformates.13
Amides can be generated from the corresponding carboxylic acids
and amines by a variety of methods. The reaction has been carried
out by a variety of methods such as anhydride, acid chloride, or
via in situ coupling agents such as dicyclohexylcarbodiimide,14 N,Nꢁ-
carbonyldiimidazole,15 benzotriazol-1-yldiethylphosphate(BDP),16 1,1ꢁ-
carbonylbis(3-methylimidazo-lium)triflate (CBMIT),17 Lawesson’s rea-
gent,18 Ti(OBu)4,19 Sn[N(TMS)2]2,20 2-ethoxy-1-(ethoxycarbonyl)-1,2-
dihydroquinoline (EEDQ),21 sulfonylchloride,22 and N,N-bis[2-oxo-3-
oxazolidinyl]phosphorodiamidic chloride.23
Extending our work on the use of N-halosulfonamides24 in organic
synthesis, we now report a convenient method for the conversion of car-
boxylic acids into esters and amides using a new, cheap, and easily made
reagent, N,Nꢁ-dibromo-N,Nꢁ-1,2-ethanediyl bis(p-toluenesulfonamide),
or BNBTS (Figure 1).24a,b,c,d
The reaction of carboxylic acids with alcohols in the presence of
BNBTS and triphenylphosphine in CH2Cl2 afforded esters without side
products (Scheme 1). The method has the advantage in terms of yields,
simplicity of the reaction conditions for the conversion, short reaction
time and no side products.
SCHEME 1
The reaction of carboxylic acids with amines in the presence of
BNBTS and triphenylphosphine in CH2Cl2 afforded amides without

Acylation and Amidation
1717
SCHEME 2
side products (Scheme 2). The method has the advantage in terms of
yields, simplicity of the reaction conditions for the conversion, short
reaction time, and no side products.
The recovered starting material (1) was rebrominated and also used
many times without reducing the yield. We believe that the reaction
is initiated via direct nucleophilic attack of triphenylphosphine at the
N-bromosulfonamide, as indicated in Scheme 3, and then reaction with
alcohol or amine affords the corresponding ester or amide in high yields.
SCHEME 3
The results of conversion of carboxylic acids into esters are presented
in Table I. The results of conversion of carboxylic acids into amides are
presented in Table II.
CONCLUSION
The advantages of BNBTS are as following:
1. The preparation of BNBTS is easy and simple.24c
2. This compound is stable for a long time under atmospheric condition
and it is a solid.

1718
A. Khazaei et al.
TABLE I Conversion of Carboxylic Acids to Esters at Room Temperature
Entry
Acid
Alcohol
Estera
Yield (%)
1
2
3
4
5
6
7
8
9
Acetic acid
Acetic acid
Hexanoic acid n-Propanol
Isoamyl alcohol
Hexanol
3-Methyl butyl ethanoate
n-Hexyl ethanoate
Propyl hexanote
Methyl hexanoate
Methyl benzoate
Benzyl formate
88
92
89
91
93
89
91
90
83
85
Hexanoic acid Methanol
Benzoic acid
Formic acid
Formic acid
Acetic acid
Benzoic acid
Maleic acid
Methanol
Benzyl alcohol
n-Propanol
n-Propanol
Propyl formate
n-Propyl acetate
2-Methyl-2-butanol 2-Methyl-2-butyl benzoateb
10
Phenol
Diphenyl maleateb
aProducts were characterized by their physical constants, comparision with authentic
samples, IR, and NMR spectra.
bProduct were not isolated, yields were obtained by 31PNMR (by calculation of the
ratio by of Ph3PO to Ph3P integration).
3. After reaction of BNBTS with substrate, the sulphonamide (1) is re-
covered and can be reused many times without decreasing the yield.
4. The isolation of products with this reagent is simple.
5. Using an excess amount of the reagent does not cause any problem
in the reaction condition.
6. The reactivity of BNBTS is high and reactions with substrate were
done at 0◦C to room temperature.
EXPERIMENTAL
Infrared (IR) and Nuclear magnetic resonance (NMR) spectra were
recorded using a Shimadzu 435-U-04 spectrophotometer and a 90 MHz
Jeol FT-NMR spectrophotometer, respectively. NMR chemical shifts
were measured relative to TMS (int; 1H).
General Procedure for the Conversion of Carboxylic
Acids to Esters
Triphenylphosphine and carboxylic acid (10 mmol of each) were dis-
solved in dichloromethane (15 ml), and then BNBTS (2.63 g) added in
small portion while the mixture was vigorously stirred.
The stirring was continued for a few minutes. The reaction mixture
was thereafter set aside at room temperature while a new solution of
alcohol (10 mmol) and pyridine (15 mmol) was being prepared; there-
after alcohol was added dropwise to the solution with vigorous stirring
and stirring was continued for a few minutes. The reaction mixture

Acylation and Amidation
1719
TABLE II Conversion of Carboxylic Acids to Amides
Entry
1
Acid
Amine
Amide
Yield (%)
90a
2
3
91b
93
4
5
92
90
6
94
7
8
84
92
Only a and b were isolated by column chromatography; the others were identified by
TLC, and their yields were obtained by 31PNMR, by integration of Ph3PO relative to
Ph3P.
was filtered and the solid (triphenylphosphine oxide, sulfonamide, and
pyridin hydrobromide) was removed, and the ester was purified by
distillation.
General Procedure for Conversion of Carboxylic
Acids to Amides
Triphenylphosphine and carboxylic acid (10 mmol) were dissolved in
dichloromethane (15 ml), and then BNBTS (2.63 g, 5 mmol) added in
small portion while the mixture was vigorously stirred. The stirring
was continued for a few minutes. The reaction mixture was thereafter
set aside at room temperature while a new solution of amine (10 mmol)
and pyridine (15 mmol) was being prepared, then the amine solution

1720
A. Khazaei et al.
was added dropwise to the solution with vigorous stirring and stirring
was continued for a few minutes. The reaction mixture was concen-
trated by evaporation of the solvent. The concentrated solution was
chromatographed through a column of silica gel with a 7:1 ratio of
petroleum benezene (40–60) to aceton as eluent. Evaporation of the
solvent gave the pure amide.
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