A convenient method for synthesis of symmetrical acid anhydrides from carboxylic acids with trichloroacetonitrile and triphenylphosphine

Article abstract of DOI:10.1081/SCC-100000529

Various carboxylic acids are converted into the corresponding carboxylic acid anhydrides treated with trichloroacetonitrile and triphenylphosphine in the presence of triethylamine at room temperature.

Full text of DOI:10.1081/SCC-100000529

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A CONVENIENT METHOD FOR SYNTHESIS OF
SYMMETRICAL ACID ANHYDRIDES FROM CARBOXYLIC
ACIDS WITH TRICHLOROACETONITRILE AND
TRIPHENYLPHOSPHINE
Joonggon Kim a & Doo Ok Jang b
a Hanwha Group Research & Engineering Center , Taejon, 305-345, Korea
b Department of Chemistry , Yonsei University , Wonju, 220-710, Korea
Published online: 09 Nov 2006.
To cite this article: Joonggon Kim & Doo Ok Jang (2001) A CONVENIENT METHOD FOR SYNTHESIS OF SYMMETRICAL
ACID ANHYDRIDES FROM CARBOXYLIC ACIDS WITH TRICHLOROACETONITRILE AND TRIPHENYLPHOSPHINE, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:3, 395-399, DOI:
10.1081/SCC-100000529
To link to this article: http://dx.doi.org/10.1081/SCC-100000529
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SYNTHETIC COMMUNICATIONS, 31(3), 395–399 (2001)
A CONVENIENT METHOD FOR
SYNTHESIS OF SYMMETRICAL ACID
ANHYDRIDES FROM CARBOXYLIC ACIDS
WITH TRICHLOROACETONITRILE AND
TRIPHENYLPHOSPHINE
Joonggon Kim1,∗ and Doo Ok Jang2
1Hanwha Group Research & Engineering Center,
Taejon 305-345, Korea
2Department of Chemistry, Yonsei University,
Wonju 220-710, Korea
ABSTRACT
Various carboxylic acids are converted into the correspond-
ing carboxylic acid anhydrides treated with trichloroacetonitrile
and triphenylphosphine in the presence of triethylamine at room
temperature.
Carboxylic acid anhydrides are used as reactive intermediates for preparing
many other functional groups in organic synthesis, due to their enhanced elec-
trophilic character of the carbonyl groups (1–8). Especially, the availability of sym-
metrical acid anhydrides is quite important for many transacylation applications
(9) because their acylation precludes the formation of by-products due to attack
at the second acyl carbonyl group of mixed anhydrides. Acid anhydrides are
∗Corresponding author.
395
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

ORDER
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396
KIM AND JANG
O
C
O
C
O
C
Ph3P / CCl3CN
Et3N, RT
R
O
R
R
OH
Scheme 1.
usually prepared by reacting carboxylate salts with powerful acylating agents,
such as acid chlorides (10), or acid anhydrides (11), or reacting carboxylic acids
with dehydrative coupling agents such as thionyl chloride (9,12), phosgene (13–
15), phosphorous pentoxide (16,17), isocyanate (18), dicyclohexylcarbodiimide
(19,20), or ethoxyacetylene (7,8,21–25). However, the methods have some draw-
backs that limit their applications: instability, high cost, toxicity, high reaction
temperature, and incompatibility with many other functional groups. We herein
report that a mild and efficient procedure for synthesis of symmetrical acid anhy-
drides from carboxylic acids with trichloroacetonitrile (TCA) and triphenylphos-
phine (TPP) (Sch. 1). According to our previous knowledge (26), it is believed
that carboxylic acid chloride, prepared in situ from carboxylic acid with combi-
nation of trichloroacetonitrile (TCA) and triphenylphosphine (TPP), undergoes
reaction with triethylammonium salt of a carboxylic acid to afford corresponding
carboxylic acid anhydride.
In the absence of triethylamine, benzoyl chloride was obtained quantita-
tively within 1 h, when benzoic acid was treated with TCA (1.3 equiv.) and
TPP (1.3 equiv.) in CH2Cl2 at room temperature (26). However, the same re-
action of benzoic acid with TCA (0.65 equiv.) and TPP (0.65 equiv.) in CH2Cl2
Table 1. Formation of Benzoic Anhydride from Benzoic Acida
Entry CCl3CN (equiv.) PPh3 (equiv.) Solvent Time (h) Yield of Anhydride (%)
1
2
0.65
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.65
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
Toluene
CH3CN
EtOAc
4
1
1
1
1
1
1
1
1
78
92
88
88
92
91
90
92
87
3b
4c
5d
6
7
8
9
aTriethylamine (1.0 equiv.) was used as a base.
b0.5 equiv. of triethylamine was used.
cAt 0◦C.
d 4-(Dimethylamino) pyridine (1.0 equiv.) was used instead of triethylamine.

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CARBOXYLIC ACID ANHYDRIDES
397
in the presence of triethylamine (1.0 equiv.) offered benzoic anhydride in 78%
along with unreacted benzoic acid, even after longer reaction time was allowed
(Table 1, Entry 1). Several controlled reactions were carried out in order to es-
tablish the optimal reaction conditions. The reaction with TCA (1.0 equiv.) and
TPP (1.0 equiv.) in the presence of TEA (1.0 equiv.) gave the highest yield of
anhydride (Entry 2). The reaction also could be carried out with 0.5 equiv. of TEA,
or at ice-water temperature, although the yield of the anhydride was somewhat
Table 2. Synthesis of Various Acid Anhydrides from Carboxylic Acids with TCA
(1.0 equiv.) and TPP (1.0 equiv.) in the Presence of TEA (1.0 equiv.) at Room
Temperature
Entry
Acid
Solventa
Time (h)
Yield of Anhydride (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
p-tButyl benzoic
p-Chloro benzoic
p-Methoxy benzoic
p-Nitro benzoic
Acetylsalicylic
Phthalic
2-Furoic
2-Thiophenecarboxylic
n-Octanoic
Palmitic
Succinic
3-Methylcrotonic
trans-Cinnamic
Phenylacetic
CH2Cl2
CH3CN
EtOAc
THF
THF
THF
1
2
2
2
2
2
2
2
4
4
3
4
2
2
2
93b
89
87
80
71c
84
80
82
77
78
79
75
83
80
76d
THF
CH2Cl2
CH2Cl2
CH2Cl2
THF
CH2Cl2
CH2Cl2
CH2Cl2
THF
3-Thienylacetic
aThese solvents were chosen depending on the solubility of the carboxylic acids.
b p-tButyl benzoic acid anhydride: 1H NMR (300 MHz, CDCl3) δ 1.37 (18H, s), 7.53
(4H, d, J = 8.1 Hz), 8.08 (4H, d, J = 8.7 Hz); 13C NMR (75 MHz, CDCl3) δ 158.7,
130.8, 130.7, 126.4, 126.1, 35.5, 31.3; Anal. calcd for C22H26O3: C, 78.07; H, 7.74; O,
14.18. Found: C, 78.3; H, 7.85.
cAcetylsalicylic acid anhydride: 1H NMR (300 MHz, CDCl3) δ 2.31 (6H, s), 7.20 (2H,
d, J = 8.7 Hz), 7.38 (2H, dd, J = 7.7 Hz, J = 8 Hz), 7.68 (2H, dd, J = 7.8 Hz,
J = 8.6 Hz), 8.08 (2H, d, J = 7.8 Hz); 13C NMR (75 MHz, CDCl3) δ 169.7, 159.6,
152.1, 133.8, 132.5, 126.5, 124.7, 122.0, 21.1; Anal. calcd for C18H14O7: C, 63.16; H,
4.12; O, 32.72. Found: C, 63.4; H, 4.23.
1
d 3-Thienylacetic acid anhydride: H NMR (300 MHz, CDCl3) δ 3.76 (4H, s), 6.92
(2H, dd, J = 1.4 Hz, J = 4.9 Hz), 7.07 (2H, d, J = 0.9 Hz), 7.29 (2H, dd, J = 3 Hz,
J = 4.9 Hz); 13C NMR (75 MHz, CDCl3) δ 170. 0, 133.8, 128.7, 126.2, 123.3, 38.6,
35.8; Anal. calcd for C12H10O3S2: C, 54.11; H, 3.78; O, 18.02; S, 24.06. Found: C,
54.0; H, 3.85; S, 24.2.

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KIM AND JANG
decreased (Entries 3 and 4). No significant difference in the yield of the anhy-
dride was observed when 4-(dimethylamino) pyridine (DMAP) was used as a base
instead of TEA (Entry 5). The reaction was carried out well in various common
organic solvents, such as tetrahydrofuran, toluene, acetonitrile, or ethyl acetate
used in organic synthesis (Entries 6–9).
EXPERIMENTAL
Typical Procedure. To a mixture of benzoic acid (244 mg, 2.0 mmol)
and triethylamine (0.28 mL, 2.0 mmol) in dry CH2Cl2 (2 mL) under argon were
added successively trichloroacetonitrile (288 mg, 2.0 mmol) and triphenylphos-
phine (524 mg, 2.0 mmol) dropwise at room temperature. The reaction mixture
was allowed to react for 1 h. The mixture was then diluted with CH2Cl2 (4 mL) and
washed with water (3 mL). The organic layer was dried over anhydrous MgSO4.
After filtration and removal of the solvent, the residue was separated with col-
umn chromatography on silica gel (hexanes/EtOAc 4:1) to give benzoic anhydride
(416 mg, 92%).
The reaction was applied for the transformation of various carboxylic acids
into the corresponding acid anhydrides under the reaction conditions. The results
are summarized in Table 2. The reaction was applicable to the conversion of
both electron-rich and electron-deficient carboxylic acids into the corresponding
anhydrides. Comparing to alkyl carboxylic acids, aryl acids gave higher yields of
the anhydrides.
The process outlined here provides several advantages over existing reac-
tions. For instance, the method does not use highly toxic reagents such as phosgene
or carbodiimides, and can be accomplished in one pot under neutral and mild re-
action conditions.
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Received in Japan January 24, 2000

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