Facile and direct synthesis of symmetrical acid anhydrides using a newly prepared powerful and efficient mixed reagent

Article abstract of DOI:10.1515/chempap-2015-0042

An efficient mixed reagent for direct synthesis of symmetrical carboxylic anhydrides from carboxylic acids has been prepared. Carboxylic acids are converted to anhydrides using triphenylphosphine/ trichloroisocyanuric acid under mild reaction conditions at room temperature. Short reaction time, excellent yields of products, low cost, availability of reagents, simple experimental procedure, and easy work-up of the products are the main advantages of the presented method.

Full text of DOI:10.1515/chempap-2015-0042

Chemical Papers 69 (3) 479–485 (2015)
DOI: 10.1515/chempap-2015-0042
ORIGINAL PAPER
Facile and direct synthesis of symmetrical acid anhydrides using
a newly prepared powerful and efficient mixed reagent
Hamed Rouhi-Saadabad, Batool Akhlaghinia*
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran
Received 31 March 2014; Revised 16 July 2014; Accepted 7 August 2014
An efficient mixed reagent for direct synthesis of symmetrical carboxylic anhydrides from car-
boxylic acids has been prepared. Carboxylic acids are converted to anhydrides using triphenylphos-
phine/trichloroisocyanuric acid under mild reaction conditions at room temperature. Short reaction
time, excellent yields of products, low cost, availability of reagents, simple experimental procedure,
and easy work-up of the products are the main advantages of the presented method.
c
ꢀ 2014 Institute of Chemistry, Slovak Academy of Sciences
Keywords: trichloroisocyanuric acid, triphenylphosphine, carboxylic acid, carboxylic anhydride,
functional group transformation
Introduction
1968; Jorba et al., 1990; Katritzky et al., 1992; Ke-
shavamurthy et al., 1982; Kim et al., 2003; Kita et
al., 1984, 1986; Mestres & Palomo, 1981; Newman &
Louge, 1971; Rinderknecht & Ma, 1964; Rinderknecht
& Guttenstein, 1967; Kocz et al., 1994; Sandler &
Karo, 1972), new and more convenient methods for
the synthesis of this class of compounds still pro-
ceeds. Carboxylic anhydrides are usually prepared
through a reaction of carboxylic acids with acylat-
ing or dehydrating coupling agents, such as acid chlo-
rides (Rambacher & Mäke, 1968), anhydrides (Sandler
& Karo, 1972), mixed carboxylic–sulfonic anhydrides
(Karimi Zarchi et al., 2010; Kazemi et al., 2004),
triphenylphosphine (PPh3)/trichloroacetonitrile (Kim
& Jang, 2001), thionyl chloride (Fife & Zhang, 1986;
Adduci & Ramirez, 1970; Kazemi & Kiasat, 2003;
Kazemi et al., 2007), phosgene (Rinderknecht & Ma,
1964; Rinderknecht & Guttenstein, 1967; Kocz et al.,
1994), phosphorus pentoxide (Burton & Kaye, 1989;
Mestres & Palomo, 1981), isocyanate (Keshavamurthy
et al., 1982), 1,3-dicyclohexylcarbodiimide (Chen &
Benoiton, 1979; Hata et al., 1968), ketene (Kita et
al., 1986), ethoxyacetylene (Tamura et al., 1987b;
Bryson & Roth, 1986; Edman & Simmons, 1968;
Eglinton et al., 1954; Kita et al., 1984, 1986; Mestres
Among the most important classes of reagents, car-
boxylic anhydrides are useful compounds either as
acylating agents or as intermediates in organic syn-
thesis due to the high electrophilic character of their
carbonyl groups (Ogliaruso & Wolfe, 1991; Mariella &
Brown, 1971; Shambhu & Digenis, 1974; Tamura et
al., 1987a, 1987b; Holzapfel & Pettit, 1985; Fukuoka
et al., 1987; Bryson & Roth, 1986). They are preferred
reactive acid derivatives for the preparation of amides,
esters, and peptides (Ogliaruso & Wolfe, 1991; Tar-
bel, 1969; Meienhofer & Gross, 1979). Mixed anhy-
drides are not suitable for many transacylation ap-
plications because the attack at the other acyl group
leads to the formation of by-products; therefore, the
availability of symmetrical anhydrides is very impor-
tant in such reactions (Fife & Zhang, 1986). Although
many reagents for the synthesis of carboxylic acid an-
hydrides have been developed (Tamura et al., 1987b;
Bryson & Roth, 1986; Fife & Zhang, 1986; Adduci
& Ramirez, 1970; Kazemi & Kiasat, 2003; Kazemi
et al., 2007; Blankemeyer-Menge et al., 1990; Bur-
ton & Kaye, 1989; Chen & Benoiton, 1979; Edman
& Simmons, 1968; Eglinton et al., 1954; Hata et al.,
*Corresponding author, e-mail: akhlaghinia@um.ac.ir
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H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015)
& Palomo, 1981; Newman & Louge, 1971), sulfated
zirconia (Hu et al., 2011), triazine reagents (Kamin´ski
et al., 2004), 4,5-dichloro-2-[(4-nitrophenyl)sulphonyl]
pyridazin-3(2H )-one (Kim et al., 2003) as well as
the reaction of carboxylate salts with powerful acy-
lating agents, such as acid chlorides (Rambacher &
Mäke, 1968; Hajipour & Mazloumi, 2002), or acid an-
hydrides (Sandler & Karo, 1972). Anhydrides have
been also prepared by the dehydration of carboxylic
acids (Wallace & Copenhaver, 1941; Rammler &
Khorana, 1963; Liesen & Sukenik, 1987) or from
acid chlorides (Serieys et al., 2008; Kim & Jang,
2009).
Experimental
General
The products were purified by column chromatog-
raphy. Purity of the products was determined by TLC
on silica gel polygram STL G/UV 254 plates (60
mesh; Merck, Germany). Melting points of the prod-
ucts were determined using an Electrothermal Type
9100 melting point apparatus (UK). FT-IR spectra
were recorded on an Avatar 370 FT-IR Thermo Nico-
let spectrometer (USA). NMR spectra for 13C NMR
1
and H NMR were provided by Brucker Avance (Ger-
However, many of these methods have major or
minor disadvantages, and the development of a new
and efficient method for the synthesis of symmetrical
anhydrides is of current interest.
many) 100 MHz and 400 MHz instruments in CDCl3
and using TMS as an internal standard. Chemical
shift is given in δ relative to TMS. Mass spectra were
recorded with a CH7A Varianmat Bremem instrument
(Germany) at 70 eV; in m/z (rel. %). Silica gel in the
size of 40–73 m that used for column chromatography
was purchased from Merck. All products are known
compounds and they were characterized by IR spec-
tral data and a comparison of their melting points
with those of authentic samples. Also, structures of
Trichloroisocyanuric acid (TCCA) in combination
with PPh3 has found widespread use in synthetic or-
ganic chemistry (Sugimoto et al., 2012; Sugimoto &
Tanji, 2005; Hiegel et al., 1999). In continuation of
our search new methods of functional group trans-
formations (Iranpoor et al., 2004a, 2004b, 2004c,
2005; Akhlaghinia, 2004, 2005a, 2005b; Akhlagh-
inia & Pourali, 2004; Akhlaghinia & Samiei, 2009;
Akhlaghinia & Rouhi-Sadabad 2013; Rouhi-Sadabad
& Akhlaghinia, 2014; Kiani et al., 2014), a direct,
mild and efficient procedure for the synthesis of var-
ious symmetrical acid anhydrides from carboxylic
acids using the prepared mixed reagent is reported
here.
1
some selected products were further confirmed by H
NMR and 13C NMR spectroscopy and by mass spec-
trometry.
General procedure for potassium carboxylate
(II) preparation
Potassium hydroxide (112.2 mg, 2 mmol) was
Table 1. Spectral data of selected prepared compounds
Compound
Spectral data
—
—
IIIa
IIIb
IIIc
IR, ν˜/cm−1: 3011 (CH-arom), 2843 (CH-aliph), 1789 and 1711 (C O), 1607 (C C)
—
—
1H NMR (400 MHz, CDCl3), δ: 8.13 (d, 4H, J = 8.0 Hz, H-arom), 7.01 (d, 4H, J = 8.0 Hz, H-arom), 3.93 (s, 6H,
2 × OCH3)
13C NMR (100 MHz, CDCl3), δ: 164.6, 162.3, 132.9, 121.3, 114.2, 55.6
IR, ν˜/cm−1: 3023 (CH-arom), 2859 (CH-aliph), 1782 and 1713 (C O), 1608 (C C)
—
—
—
—
1H NMR (100 MHz, CDCl3), δ: 7.75 (s, 4H, H-arom ), 7.26 (s, 2H, H-arom), 2.40 (s, 12H, 4 × CH3)
MS, m/z (Ir/%): 282 (5) (M+) 149 (10) (M+ – (Me)2PhCO), 133 (100) ((Me)2PhCO), 105 (88) ((Me)2PhCO), 91
(30) (PhCH2)
IR, ν˜/cm−1: 3059 (CH-arom), 2912 (CH-aliph), 1774 and 1713 (C O), 1609 (C C)
—
—
—
—
1H NMR (400 MHz, CDCl3), δ: 8.07 (d, 4H, J = 8.0 Hz, H-arom), 7.34 (d, 4H, J = 8.0 Hz, H-arom), 2.48 (s, 6H,
2 × CH3)
13C NMR (100 MHz, CDCl3), δ: 162.6, 145.6, 130.7, 129.6, 126.2, 21.9
—
—
IIId
IIIk
IIIo
IR, ν˜/cm−1: 3064 (CH-arom), 1785 and 1724 (C O), 1598 (C C)
—
—
1H NMR (400 MHz, CDCl3), δ: 8.19 (dt, 4H, J = 8.4 Hz, J = 1.6 Hz, H-arom), 7.71 (tt, 2H, J = 5.6 Hz, J = 1.6 Hz,
H-arom), 7.56 (td, 4H, J = 7.2 Hz, J = 1.6 Hz, H-arom)
IR, ν˜/cm−1: 3023 (CH-arom), 2933 (CH-aliph), 1801 and 1736 (C O), 1699 (C C)
—
—
—
—
1
—
—
H NMR (400 MHz, CDCl3), δ: 7.38–7.20 (m, 20H, H-arom), 5.07 (s, 2H, 2 × (Ph)2CH—C O)
13C NMR (100 MHz, CDCl3), δ: 167.6, 136.9, 128.8, 128.7, 127.7, 57.9
IR, ν˜/cm−1: 3066 and 3023 (CH-arom), 1768 and 1701 (C O), 1631 (C
C
), 1450 (C Carom)
—
—
—
—
—
—
vinyl
1
—
H NMR (100 MHz, CDCl3), δ: 7.75 (d, 2H, J = 16.0 Hz, PhCH ), 7.68–7.31 (m, 10H, H-arom), 6.52 (d, 2H, J =
—
—
16.0 Hz, PhCH
)
—
MS, m/z (Ir/%): 278 (40) (M+) 149 (23) (M+ – PhCH CHCO), 130 (100) (PhCH CHCO), 103 (95) (PhCH CH),
—
—
—
—
—
—
91 (75) (PhCH2), 77 (95) (Ph)
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481
Table 2. Conversion of benzoic acid to benzoic anhydride using the PPh3/TCCA/PhCOOK system under different reaction
conditions
Entry
Solvent
PPh3/TCCA/PhCOOH/PhCOOK mole ratio
Time/h
Yielda/%
1
2
3
4
5
6
7
8
9
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
THF
1 : 1 : 1 : 1
1 : 1 : 1 : 1.5
1 : 1 : 1 : 2
5
3
2
2
2
2
5
4
75
80
85
85
85
80
75
70
90
95
90
85
1 : 1 : 1 : 2.5
1 : 0.3 : 1 : 2.5
1 : 0.3 : 1 : 2
1 : 0.3 : 1 : 1
1 : 0.3 : 0.5 : 1
1 : 0.3 : 0.5 : 2
1 : 0.3 : 0.5 : 2
1 : 0.3 : 0.5 : 2
1 : 0.3 : 0.5 : 2
50b
50b
1
10
11
12
EtOAc
70b
a) Yields refer to the isolated products; b) in min.
added to a solution of carboxylic acid (2 mmol) in
distilled water. The solution was stirred at room tem-
perature for 30 min. Evaporation of the solvent gave
crystals of potassium carboxylate salt.
General procedure for benzoic anhydride (IIId)
preparation
Fig. 1. Direct synthesis of symmetric anhydrides (III) from
carboxylic acids (I); i) PPh3, TCCA, CH2Cl2, 0◦C→
r.t.; for substituent specification see Table 3.
To a cold solution of TCCA (77.4 mg, 0.3 mmol)
in CH2Cl2 (3–5 mL), PPh3 (262.3 mg, 1 mmol) was
added at 0–5◦C under stirring. A white suspension was
formed to which benzoic acid (121.3 mg, 1 mmol) was
added and the stirring continued for 15 min at room
temperature. Potassium benzoate (322.2 mg, 2 mmol)
was added and the stirring was continued for further
50 min at room temperature. After the completion of
the reaction (monitored by TLC), the mixture was
washed with cold distilled water (2 × 10 mL). The
organic layer was dried with anhydrous Na2SO4, and
passed through a short silica-gel column using hex-
ane/ethyl acetate (ϕr = 10 : 1) as the eluent. IIId was
obtained in a 95 % yield (214.7 mg) after the solvent
was removed under reduced pressure. Selected spec-
tral data of six representative products are given in
Table 1.
8). Applying the 1 : 0.3 : 0.5 : 2 mole ratio of
PPh3/TCCA/RCO2H/RCOOK in CH3CN gave the
same result as in CH2Cl2 (Table 2, Entry 9). The
selected solvent for this transformation was CH2Cl2
which is less expensive than CH3CN. These re-
actions revealed that even simple stirring of this
PPh3/TCCA/PhCOOH/PhCOOK system in CH2Cl2
at room temperature affects the formation of ben-
zoic anhydride in a 95 % isolated yield within 50 min
(Table 2, Entry 10). However, the same reaction in
tetrahydrofuran (THF) and ethyl acetate (EtOAc) af-
forded benzoic anhydride in a 85–90 % yield in longer
reaction time (Table 2, Entries 11 and 12).
The present method can be generally applied
for a range of structurally diverse carboxylic acids.
Aliphatic and aromatic carboxylic acids can be thus
converted into their corresponding anhydrides in high
isolated yields. The scope and generality of this pro-
cess is illustrated using several examples and the re-
sults are summarized in Table 3.
Structure of the products was determined from
their spectral data (IR, 1H NMR, and 13C NMR),
and by its direct comparison with authentic samples.
The 13C NMR signal at around δ 160 was assigned
to the carbonyl carbon of anhydride. Two strong and
sharp absorption bands at 1808–1763 cm−1 and at
1737–1701 cm−1 in the FT-IR spectra were assigned
Results and discussion
Direct preparation of carboxylic anhydrides from
carboxylic acids is still in great demand. In this pa-
per, an efficient and convenient method for the prepa-
ration of symmetrical carboxylic anhydrides from the
corresponding carboxylic acids using a PPh3/TCCA
mixed reagent in the presence of RCOOK is presented.
General reaction is outlined in Fig. 1.
Several controlled reactions were carried out to es-
tablish the optimal reaction conditions. The influence
of different molar ratios of PPh3/TCCA/PhCOOH/
PhCOOK in CH3CN was studied: the 1 : 0.3 : 0.5 : 2
mole ratio provided the shortest reaction time and
the highest yields obtained (Table 2, Entries 1–
—
to the asymmetric and symmetric C O stretching vi-
—
brations, respectively.
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H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015)
Table 3. Synthesis of carboxylic acid anhydrides from carboxylic acids using the PPh3/TCCA/RCOOK system
Isolated Reported
Entry Compound Carboxylic acid
Time/min yield/% M.p./◦C M.p./◦C References
1
2
3
4
5
6
7
8
9
10
11
12
13
14
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
IIIk
IIIl
IIIm
IIIn
4-MeOC6H4COOH
3,5-Me2C6H3COOH
4-MeC6H4COOH
PhCOOH
4-BrC6H4COOH
4-ClC6H4COOH
3,4-Cl2C6H3COOH
4-NO2C6H4COOH
3-NO2C6H4COOH
PhCH2COOH
40
35
40
50
65
97
98
90
95
93
94
95
96
92
96
97
97
95
95
89–91
88–93
Park et al. (2005)
131–133 132–133 Tachibana et al. (2006)
78–79
41–43
78–80
42–44
Hu et al. (1997)
Park et al. (2005)
219–220 218–220 Hu et al. (1997)
191–193 192–193 Park et al. (2005)
146–148 147–149 Rosowsky et al. (1998)
173–176 172–176 Hu et al. (1997)
160–162 161–163 Hu et al. (1997)
71–72
96–98
77–78
69–71
20–22
90
100
120
120
80
85
75
72–72.5 Jenkins and Cohen (1975)
(Ph)2CHCOOH
4-MeOPhCH2COOH
CH3(CH2)15CH2COOH
97–98
76–78
70–72
22
Brady and O’Neal (1967)
Roof et al. (1976)
Hu et al. (1997)
75
90
—
—
CH3(CH2)7CH
Sonntag et al. (1954)
CH(CH2)6CH2COOH
—
15
16
17
18
19
20
IIIo
IIIp
IIIq
IIIra
IIIs
IIIt
(E)-PhCH CHCOOH
90
120
180
60
120
120
95
98
97
95
92
97
134–136 135–137 Hu et al. (1997)
—
—
4-ClPhCH CHCOOH
185–187
204–206
187
206
Exner and Jehlicka (1970)
Hurd and Thomas (1933)
—
—
—
3-NO2PhCH CHCOOH
phtalic acid
pyridine-4-carboxylic acid
thiophene-3-carboxylic acid
130–132 131–132 Kimura et al. (2012)
101–103 102–104 Funasaka and Mukaiyama (2008)
48–50
50–52
Funasaka and Mukaiyama (2008)
a) Reaction was carried out in the presence of triethylamine.
Fig. 2. Proposed mechanism for direct synthesis of anhydrides (III) from carboxylic acids.
In order to gain deeper insight into the general ap-
plicability of this method, optimized conditions were
applied in the reaction of different classes of carboxylic
acids with this mixed reagent system. The results re-
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H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015)
483
vealed that the reaction can be employed for a wide
range of carboxylic acids. Aromatic carboxylic acids
with electron donating substituents were successfully
converted into their corresponding carboxylic anhy-
drides in a short time and with high yields (Table 3,
Entries 1–4), whereas the reaction of aromatic car-
boxylic acids with electron withdrawing groups, cin-
namic acids, and hetero aromatic acids required longer
reaction time to reach such excellent yields due to very
poor nucleophilicity of the corresponding carboxylate
ions (Table 3, Entries 5–9 and 15–17 and 19–20). On
basis of the mechanism proposed in our previous re-
search (Akhlaghinia & Rouhi-Saadabad, 2013) (Fig. 2)
and results obtained from Table 3, nucleophilic attack
of the carboxylate ion on V yielding triphenylphos-
phine oxide and the corresponding carboxylic anhy-
drides is the rate determining step. The stronger the
nucleophiles are, the faster is the product formation.
The FT-IR spectrum of [1,3,5]triazine-2,4,6-triol (VI )
which is in equilibrium with [1,3,5]triazinane-2,4,6-
trione (VII ) showed two very strong and sharp bands
at 3200 cm−1 ascribed to the OH and NH and at
the synthesis of symmetrical acid anhydrides using
the PPh3/TCCA/RCO2H/RCOOK system with ex-
cellent yields and high product purity has been de-
scribed. This procedure has the following advantages:
(i) direct conversion of acids to anhydrides in a short
reaction time at room temperature; (ii) mild reaction
conditions; (iii) safety of the process, low cost, and
availability of reagents; (iv) simple experimental pro-
cedure and; (v) easy work-up of the products.
Acknowledgements. The authors gratefully acknowledge the
partial support of this study by the Ferdowsi University of
Mashhad Research Council (Grant no. p/3/19312).
Supplementary data
Supplementary data associated with this article
can be found in the online version of this paper (DOI:
10.1515/chempap-2015-0042).
References
Adduci, J. M., & Ramirez, R. S. (1970). Anhydride formation
with thionyl chloride. Organic Preparations and Procedures
International, 2, 321–325. DOI: 10.1080/00304947009458638.
Akhlaghinia, B. (2004). Efficient conversion of tetrahydropy-
ranyl (THP) ethers to their corresponding cyanides with
triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone/
n-Bu4NCN. Phosphorus, Sulfur, and Silicon and the Related
Elements, 179, 1783–1786. DOI: 10.1080/10426500490466463.
Akhlaghinia, B., & Pourali, A. R. (2004). Novel and highly se-
lective conversion of alcohols and thiols to alkyl nitrites with
triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone/
Bu4NNO2 system. Synthesis, 2004, 1747–1749. DOI: 10.1055
/s-2004-829122.
Akhlaghinia, B. (2005a). Triphenylphosphine/2,3-dichloro-5,6-
dicyanobenzoquinone in the presence of n-Bu4NN3 is a useful
system for efficient conversion of tetrahydropyranyl (THP)
ethers to their corresponding alkyl azides. Phosphorus, Sul-
fur, and Silicon and the Related Elements, 180, 1601–1604.
DOI: 10.1080/104265090884292.
1749 cm−1 ascribed to the C O stretching vibrations,
—
—
respectively.
Also, the reaction with aliphatic acids provides
high yields of their corresponding carboxylic acid an-
hydrides in a short reaction time (Table 3, Entries
10–14).
Dicarboxylic acids, such as phthalic acid, in the
presence of PPh3/TCCA, triethylamine, and in the
absence of potassium carboxylate are cleanly, eas-
ily, and efficiently converted into their corresponding
cyclic anhydrides in high isolated yields (Table 3, En-
try 18). The same conditions were also applicable only
for monocarboxylic acids with electron donor groups
due to the high nucleophilicity of their carboxylate
ions.
To further study the proposed mechanism, and to
find the influence of PPh3, the reaction was carried out
in the absence of PPh3. Neither carboxylic anhydride
as the product nor acyl chloride as the by-product was
obtained. The fact that no reaction occurs without
PPh3 suggests that TCCA acts as a carboxyl group
activator only in the presence of PPh3.
Akhlaghinia, B. (2005b).
A new and convenient method
of generating alkyl isocyanates from alcohols, thiols and
trimethylsilyl ethers using triphenylphosphine/2,3-dichloro-
5,6-dicyanobenzoquinone/Bu4 NOCN. Synthesis, 2005, 1955–
1958. DOI: 10.1055/s-2005-869906.
Akhlaghinia, B., & Samiei, S. (2009). Triphenylphosphine/2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ)/[n-Bu4N]OCN as
a useful system for the efficient conversion of tetrahydropy-
ranyl (THP) ethers to the corresponding alkyl isocyanates.
Phosphorus, Sulfur, and Silicon and the Related Elements,
184, 2525–2529. DOI: 10.1080/10426500802508212.
Akhlaghinia, B., & Rouhi-Saadabad, H. (2013). Direct and
facile synthesis of acyl azides from carboxylic acids using the
trichloroisocyanuric acid–triphenylphosphine system. Cana-
dian Journal of Chemistry, 91, 181–185. DOI: 10.1139/cjc-
2011-0493.
Blankemeyer-Menge, B., Nimtz, M., & Frank, R. (1990). An
efficient method for anchoring fmoc-anino acids to hydroxyl-
functionalised solid supports. Tetrahedron Letters, 31, 1701–
1704. DOI: 10.1016/s0040-4039(00)88858-9.
Also, the reaction was carried out in the absence
of potassium carboxylate ions to find any carboxylic
acid chlorides species formed as intermediates or by-
products of carboxylic acids transformation to their
corresponding anhydrides. It is noteworthy that no
evidence of the formation of carboxylic acid chlorides
was observed. As the temperature was retained be-
◦
tween 0–5 C, before the addition of potassium car-
boxylate, any interaction between V and chloride ions
was prevented.
Conclusions
Brady, W. T., & O’Neal, H. R. (1967). Further studies on the
mechanism of diphenylketene cycloaddition. Journal of Or-
ganic Chemistry, 32, 2704–2702. DOI: 10.1021/jo01284a013.
In conclusion, a useful and practical method for
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484
H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015)
Bryson, T. A., & Roth, G. A., (1986). Synthetic studies di-
rected at the B/C ring systems of CC-1065; preparation of
substituted cyclopropyl indolenones. Tetrahedron Letters, 27,
3689–3692. DOI: 10.1016/s0040-4039(00)83854-x.
Burton, S. G., & Kaye, P. T. (1989). A convenient preparation
of carboxylic acid anhydrides using a “supported” phospho-
rus pentoxide reagent. Synthetic Communications, 19, 3331–
3335. DOI: 10.1080/00397918908052736.
Chen, F. M. F., & Benoiton, N. L. (1979). A general method
for formylating sensitive amino acid esters. Synthesis, 1979,
709–710. DOI: 10.1055/s-1979-28805.
Edman, J. R., & Simmons, H. E. (1968). Bicyclo[2.2.1]hepta-
2,5-diene-2,3-dicarboxylic anhydride. Journal of Organic
Chemistry, 33, 3808–3816. DOI: 10.1021/jo01274a028.
Eglinton, G., & Jones, E. R. H., Shaw, B. L., & Whiting, M. C.
(1954). Researches on acetylenic compounds. Part XLIII. A
new method for the preparation of alkoxyacetylenes Journal
of the Chemical Society, 1954, 1860–1865.
Exner, O., & Jehlicka, E. (1970). Dipole moments and confor-
mation of carboxylic acid anhydrides. Collection of Czecho-
slovak Chemical Communications, 35, 1514–1521. DOI:
10.1135/cccc19701514.
Fife, W. K., & Zhang, Z. D. (1986). Phase managed organic
synthesis 3. Symmetrical anhydrides from carboxylic acids
via polymer assisted reaction. Tetrahedron Letters, 27, 4937–
4940. DOI: 10.1016/s0040-4039(00)85101-1.
Fukuoka, S., Takimoto, S., Katsuki, T., & Yamaguchi, M.
(1987). Activation of mixed carboxylic α-bromotoluoyl an-
hydrides by silver tetraflouroborate. Synthesis of ester
and thiol esters. Tetrahedron Letters, 28, 4711–4712. DOI:
10.1016/s0040-4039(00)96605-x.
Funasaka, S., & Mukaiyama, T. (2008). A versatile, practical,
and inexpensive reagent, pyridine-3-carboxylic anhydride (3-
PCA), for condensation reactions. Bulletin of the Chemical
Society of Japan, 81, 148–159. DOI: 10.1246/bcsj.81.148.
Hajipour, A. R., & Mazloumi, G. (2002). An efficient and sim-
ple procedure for preparation of esters and anhydrides from
acid chlorides in the presence of 1,4-diazabicyclo[2.2.2]octane
(dabco) under solvent-free conditions. Synthetic Communi-
cations, 32, 23–30. DOI: 10.1081/scc-120001504.
trimethylsilyl ethers, and carboxylates to thiocyanates with
triphenylphosphine/diethylazodicarboxylate/NH4 SCN. Syn-
thesis, 2004, 92–96. DOI: 10.1055/s-2003-44369.
Iranpoor, N., Firouzabadi, H., Akhlaghinia, B., & Nowrouzi,
N. (2004b). Conversion of alcohols, thiols, and trimethysi-
lyl ethers to alkyl cyanides using triphenylphosphine/2,3-
dichloro-5,6-dicyanobenzoquinone/n-Bu4 NCN. Journal of
Organic Chemistry, 69, 2562–2564. DOI: 10.1021/jo035238v.
Iranpoor, N., Firouzabadi, H., Akhlaghinia, B., & Nowrouzi,
N. (2004c). A novel and highly selective conversion of alco-
hols, thiols, and silyl ethers to azides using the triphenylphos-
phine/2,3-dichloro-5,6-dicyanobenzoquinone(DDQ)/n-
Bu4NN3 system. Tetrahedron Letters, 45, 3291–3294. DOI:
10.1016/j.tetlet.2004.02.141.
Iranpoor, N., Firouzabadi, H., Azadi, R., & Akhlaghinia, B.
(2005). Highly selective conversion of 1◦ and 2◦ tetrahy-
dropyranyl ethers to thiocyanates and 3◦ ones to isoth-
iocyanates using triphenylphosphine/diethyl azodicarboxy-
late/NH4SCN. Journal of Sulfur Chemistry, 26, 133–137.
DOI: 10.1080/17415990500135228.
Jenkins, J. A., & Cohen, J. (1975). Deuterium isotope effects
and the influence of solvent in the redox and rearrange-
ment reactions of 2-picoline N-oxide and phenylacetic an-
hydride. Journal of Organic Chemistry, 40, 3566–3571. DOI:
10.1021/jo00912a021.
Jorba, X., Albericio, F., Grandas, A., Bannwarth, W., & Giralt,
E. (1990). Arenesulphonyltriazolides as condensing reagents
in solid phasepeptide synthesis. Tetrahedron Letters, 31,
1915–1918. DOI: 10.1016/s0040-4039(90)80004-6.
Kamin´ski, Z. J., Kolesin´ska, B., & Marcinkowska, M. (2004).
Mild and efficient synthesis of carboxylic acid anhydrides
from carboxylic acids and triazine coupling reagents. Syn-
thetic Communications, 34, 3349–3358. DOI: 10.1081/scc-
200030581.
Karimi Zarchi, M. A., Mirjalili, B. F., Shamsi Kahrizsangi, Z., &
Tayefi, M. (2010). A mild, clean, and simple synthesis of sym-
metrical carboxylic anhydrides from carboxylic acids using
a polymer supported tosyl chloride. Journal of the Iranian
Chemical Society, 7, 455–460. DOI: 10.1007/bf03246032.
Katritzky, A. R., Shobana, N., Pernak, J., Afridi, A. S., & Fan,
W. Q. (1992). Sulfonyl derivatives of benzotriazole: Part 1. A
novel approach to the activation of carboxylic acids. Tetrahe-
dron, 48, 7817–7822. DOI: 10.1016/s0040-4020(01)80459-2.
Kazemi, F., & Kiasat, A. R. (2003). Dabco/SOCl2, mild,
and convenient reagent for the preparation of symmetri-
cal carboxylic acid anhydrides. Phosphorus, Sulfur, and
Silicon and the Related Elements, 178, 2287–2291. DOI:
10.1080/713744563.
Hata, T., Tajima, K., & Mukaiyama, T. (1968). A convenient
method for the preparation of acid anhydrides from metallic
carboxylates. Bulletin of the Chemical Society of Japan, 41,
2746–2747. DOI: 10.1246/bcsj.41.2746.
Hiegel, G. A., Ramirez, J., & Barr, R. K. (1999). Chlorine sub-
stitution reactions using trichloroisocyanuric acid with triph-
enylphosphin. Synthetic Communications, 29, 1415–1419.
DOI: 10.1080/00397919908086119.
Holzapfel, C. W.,
&
Pettit, G. R. (1985). Antineoplastic
Kazemi, F., Sharghi, H., & Naseri, M. A. (2004). A cheap, sim-
ple and efficient method for the preparation of symmetri-
cal carboxylic acid anhydrides. Synthesis, 2, 205–207. DOI:
10.1055/s-2003-44381.
Kazemi, F., Kiasat, A. R., & Mombaini, B. (2007). Simple
preparation of symmetrical carboxylic acid anhydrides by
means of Na2CO3/SOCl2. Synthetic Communications, 37,
3219–3223. DOI: 10.1080/00397910701547904.
Keshavamurthy, K. S., Vankar, Y. D., & Dhar, D. N. (1982).
Preparation of acid anhydrides, amides, and esters using
chlorosulfonyl isocyanate as a dehydrating agent. Synthesis,
1982, 506–508. DOI: 10.1055/s-1982-29859.
Kiani, A., Akhlaghinia, B., Rouhi-Saadabad, H., & Bakavoli,
M. (2014). Direct synthesis of sulfonyl azides from sul-
fonic acids. Journal of Sulfur Chemistry, 35, 119–127. DOI:
10.1080/17415993.2013.801476.
agents. Part 108. Structural biochemistry. Part 23. Syn-
thesis of the dolastatin thiazole amino acid component
(gln)Thz. Journal of Organic Chemistry, 50, 2323–2327.
DOI: 10.1021/jo00213a024.
Hu, Y. L., Wang, J. X.,
& Li, S. H. (1997). Synthe-
sis of anhydrides fom acyl chlorides under ultrasound
condition. Synthetic Communications, 27, 243–248. DOI:
10.1080/00397919708005024.
Hu, Y. L., Zhao, X. E., & Lu, M. (2011). Efficient and conve-
nient synthesis of symmetrical carboxylic anhydrides from
carboxylic acids with sulfated zirconia by phase transfer
catalysis. Bulletin of the Chemical Society of Ethiopia, 25,
255–262. DOI: 10.4314/bcse.v25i2.65900.
Hurd, C. D., & Thomas, C. L. (1933). The interaction of ketene
with aromatic aldehydes and its bearing on the Perkin re-
action. Journal of the American Chemical Society, 55, 275–
283. DOI: 10.1021/ja01328a033.
Iranpoor, N., Firouzabadi, H., Akhlaghinia, B., & Azadi, R.
(2004a). Conversion of alcohols, thiols, carboxylic acids,
Kim, J. G., & Jang, D. O. (2001). A convenient method for syn-
thesis of symmetrical acid anhydrides from carboxylic acids
with trichloroacetonitrile and triphenylphosphine. Synthetic
Communications, 31, 395–399. DOI: 10.1081/scc-100000529.
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H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015)
485
Kim, J. J., Park, Y. D., Lee, W. S., Cho, S. D., & Yoon,
Y. J. (2003). Facile synthesis of carboxylic anhydrides us-
ing 4,5-dichloro-2-[(4-nitrophenyl)sulfonyl]pyridazin-3(2H )-
one. Synthesis, 10, 1517–1520. DOI: 10.1055/s-2003-40512.
Kim, J. G., & Jang, D. O. (2009). Synthesis of symmetrical car-
boxylic acid anhydrides from acyl chlorides in the presence of
in metal and DMF. Bulletin of the Korean Chemical Society,
30, 27–28. DOI: 10.5012/bkcs.2009.30.1.027.
Kimura, Y., Matsuura, D., Hanawa, T., & Kobayashi, Y. (2012).
New preparation method for Vilsmeier reagent and related
imidoyl chlorides. Tetrahedron Letters, 53, 1116–1118. DOI:
10.1016/j.tetlet.2011.12.087.
Roof, A. A. M., van-Woerden, H. F., & Cerfontain, H. (1976).
The photochemistry of α-aryl carboxylic anhydrides—II:
Photolysis of some substituted phenylacetic anhydrides
Tetrahedron, 32, 2967–2971. DOI: 10.1016/0040-4020(76)
80154-8.
Rosowsky, A., Bader, H., Cucchi, C. A., Moran, R. G., Kohler,
W., & Freisheim, J. H. (1988). Methotrexate analogs. 33.
N.delta.-acyl-N.alpha.-(4-amino-4-deoxypteroyl)-L-ornithine
derivatives. Synthesis and in vitro antitumor activity. Jour-
nal of Medicinal Chemistry, 31, 1332–1337. DOI: 10.1021/
jm00402a013.
Rouhi-Saadabad, H., & Akhlaghinia, B. (2014). Direct, rapid
and convenient synthesis of esters and thioesters using
PPh3/N-chlorobenzotriazole system. Journal of the Brazil-
ian Chemical Society, 25, 253–263. DOI: 10.5935/0103-
5053.20130291.
Kita, Y., Akai, S., Yoshigi, M., Nakajima, Y., Yasuda, H.,
& Tamura, Y. (1984). A mild and facile synthesis of car-
boxylic anhydrides. Tetrahedron Letters, 25, 6027–6030. DOI:
10.1016/s0040-4039(01)81751-2.
Kita, Y., Akai, S., Ajimura, N., Yoshigi, M., Tsugoshi, T., Ya-
suda, H., & Tamura, Y. (1986). Facile and efficient synthe-
ses of carboxylic anhydrides and amides using (trimethylsi-
lyl)ethoxyacetylene. Journal of Organic Chemistry, 51,
4150–5158. DOI: 10.1021/jo00372a010.
Kocz, R., Roestamadi, J., & Mobashery, S. (1994). A convenient
triphosgene-mediated synthesis of symmetric carboxylic acid
anhydrides. Journal of Organic Chemistry, 59, 2913–2914.
DOI: 10.1021/jo00089a046.
Sandler, S. R., & Karo, W. (1972). Organic functional group
preparations. Waltham, MA, USA: Academic Press.
Serieys, A., Botuha, C., Chemla, F., Ferreira, F., & Pérez-Luna,
A. (2008). Zinc(0)/dimethylformamide-mediated synthesis
of symmetrical carboxylic anhydrides from acid chlorides.
Tetrahedron Letters, 49, 5322–5323. DOI: 10.1016/j.tetlet.
2008.06.073.
Shambhu, M. B., & Digenis, G. A. (1974). Insoluble resins with
mixed carbonic-carboxylic anhydride functions. Preparation
and applications as mild selective acylating reagents. Journal
of the Chemical Society, Chemical Communications, 1974,
619–620. DOI: 10.1039/c39740000619.
Liesen, G. P., & Sukenik, C. N. (1987). Activated anhydrides of
tartaric and malic acids. Journal of Organic Chemistry, 52,
455–457. DOI: 10.1021/jo00379a030.
Mariella, R. P., & Brown, K. H. (1971). A novel SN1 dis-
placement: The reaction of tertiary amines with acetic anhy-
dride. Canadian Journal of Chemistry, 49, 3348–3351. DOI:
10.1139/v71-557.
Sonntag, N. O. V., Trowbridge, J. R., & Krems, I. J. (1954).
Reactions of fatty acid chlorides. I. Preparation of fatty acid
anhydrides. Journal of the American Oil Chemists’ Society,
31, 151–157. DOI: 10.1007/bf02545703.
Meienhofer, J., & Gross, E. (1979). The peptides: Analysis, syn-
thesis and biology. Waltham, MA, USA: Academic Press.
Mestres, R., & Palomo, C. (1981). Phosphorus in organic chem-
istry; I. Mild and convenient reagents for the preparation
of symmetrical carboxylic acid anhydrides. Synthesis, 1981,
218–220. DOI: 10.1055/s-1981-29391.
Sugimoto, O., & Tanji, K. I. (2005). An improved method for
chlorination of nitrogen-containing π-deficient heteroaromat-
ics using triphenylphosphine and trichloroisocyanuric acid.
Heterocycles, 65, 181–185. DOI: 10.3987/com-04-10245.
Sugimoto, O., Harada, Y., & Tanji, K. I. (2012). Phosphonium
chloride as a non-volatile chlorinating reagent: preparation
and reaction in no solvent or ionic liquid. Heterocycles, 86,
1583–1590. DOI: 10.3987/com-12-s(n)105.
Tachibana, Y., Kawasaki, H., Kihara, N., & Takata, T. (2006).
Sequential O- and N-acylation protocol for high-yield prepa-
ration and modification of rotaxanes: Synthesis, functional-
ization, structure, and intercomponent interaction of rotax-
anes. Journal of Organic Chemistry, 71, 5093–5104. DOI:
10.1021/jo0601563.
Tamura, Y., Kirihara, M., Sasho, M., Akai, S., Sekihachi, J.,
Okunaka, R., & Kita, Y. (1987a). Total synthesis of a D-
ring indole analogue of daunomycin. Journal of the Chemical
Society, Chemical Communications, 1987, 1474–1476. DOI:
10.1039/c39870001474.
Tamura, Y., Kirihara, M., Sekihachi, J. I., Okunaka, R.,
Mohri, S. I., Tsugoshi, T., Akai, S., Sasho, M., & Kita, Y.
(1987b). A new synthetic strategy for heteroanthracyclines:
Total synthesis of D-ring thiophene analogs of daunomycin.
Tetrahedron Letters, 28, 3971–3974. DOI: 10.1016/s0040-
4039(00)96434-7.
Newman, M. S., & Louge, M. W. (1971). Synthesis of 6,6ꢀ-
diethynyldiphenic anhydride. Journal of Organic Chemistry,
36, 1398–1401. DOI: 10.1021/jo00809a018.
Ogliaruso, M. A., & Wolfe, J. F. (1991). Synthesis of carboxylic
acids, esters and their derivatives. New York, NY, USA: Wi-
ley.
Park, Y. D., Kim, J. J., Kim, H. K., Cho, S. D., Kang,
Y. J., Park, K. H., Lee, S. G., & Yoon, Y. J. (2005).
ZnCl2-mediated synthesis of carboxylic anhydrides using 2-
acyl-4,5-dichloropyridazin-3(2H )-ones. Synthetic Communi-
cations, 35, 371–378. DOI: 10.1081/scc-200048939.
Rambacher, P., & Mäke, S. (1968). Simplified process for prepa-
ration of anhydrides of aromatic acids. Angewandte Chemie
International Edition, 7, 465. DOI: 10.1002/anie.196804651.
Rammler, D. H.,
& Khorana, H. G. (1963). Studies on
polynucleotides. XX.1 Amino acid acceptor ribonucleic acids
(1). The synthesis and properties of 2ꢀꢀ (or 3ꢀꢀ)-O-(DL-
phenylalanyl)-adenosine, 2ꢀꢀ (or 3ꢀꢀ)-O-(DL-phenylalanyl)-
uridine and related compounds. Journal of the American
Chemical Society, 85, 1997–2002. DOI: 10.1021/ja00896a020.
Rinderknecht, H., & Ma, V. (1964). Eine einfache neue Synthese
fu¨r Säureanhydride. Helvetica Chimica Acta, 47, 162–165.
DOI: 10.1002/hlca.19640470121. (in German)
Tarbel, D. S. (1969). Carboxylic carbonic anhydrides and re-
lated compounds. Accounts of Chemical Research, 2, 296–
300. DOI: 10.1021/ar50022a002.
Wallace, J. M., Jr., & Copenhaver, J. E. (1941). Anhydrides
of the normal aliphatic saturated monobasic acids. Jour-
nal of the American Chemical Society, 63, 699–700. DOI:
10.1021/ja01848a017.
Rinderknecht, H., & Guteinstein, M. (1967). Nicotinic anhy-
dride. Organic Syntheses, 47, 89. DOI: 10.15227/orgsyn.047.
0089.
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