Acyl iodides in organic synthesis: IV. Reaction of acetyl iodide with carboxylic acids

Article abstract of DOI:10.1023/B:RUJO.0000019730.43667.46

In contrast to acyl chlorides, reactions of acetyl iodide with monocarboxylic acids follow the exchange pattern to give the corresponding acyl iodides and acetic acid. The reaction attracts interest from the preparative viewpoint as a simple and convenient route to acyl iodides. Acetyl iodide reacts with phthalic acid, yielding acetic acid and phthalic anhydride, while the reaction of acetyl iodide with oxalic acid leads to formation of acetic acid, carbon(II) oxide, and molecular iodine.

Full text of DOI:10.1023/B:RUJO.0000019730.43667.46

Russian Journal of Organic Chemistry, Vol. 39, No. 12, 2003, pp. 1702 1705. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 12, 2003,
pp. 1774 1777.
Original Russian Text Copyright
2003 by Voronkov, Belousova, Trukhina, Vlasova.
Dedicated to Full Member of the Russian Academy of Sciences
B.A. Trofimov on the 65th Anniversary of His Birth
Acyl Iodides in Organic Synthesis: IV.* Reaction
of Acetyl Iodide with Carboxylic Acids
M. G. Voronkov, L. I. Belousova, A. A. Trukhina, and N. N. Vlasova
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: voronkov@irioch.irk.ru
Received May 6, 2003
Abstract In contrast to acyl chlorides, reactions of acetyl iodide with monocarboxylic acids follow the
exchange pattern to give the corresponding acyl iodides and acetic acid. The reaction attracts interest from
the preparative viewpoint as a simple and convenient route to acyl iodides. Acetyl iodide reacts with phthalic
acid, yielding acetic acid and phthalic anhydride, while the reaction of acetyl iodide with oxalic acid leads
to formation of acetic acid, carbon(II) oxide, and molecular iodine.
It was found previously that trialkyliodosilanes
readily cleave C O C, C O Si, and Si O Si
moieties in the absence of a catalyst [4 6]. In 1975,
the possibility of using trimethyliodosilane in organic
synthesis was demonstrated for the first time [5 9].
We have recently started a search for organic reagents
which can be regarded as synthetic equivalents of
trimethyliodosilane or alternative to it. Acyl iodides
RCOI turned out to be excellent iodinating, deoxy-
genating, and acylating agents capable of reacting
according to both homolytic and heterolytic patterns
and often yielding unexpected products [1 3, 10].
As compared to other acyl halides RCOX (X = F,
Cl, Br), acyl iodides remain poorly studied, presum-
ably because of their instability. For example, only
a few publications on acyl iodides were cited in the
monograph [11] dealing with acyl halides.
halides MeCOX, where X = F, Cl, Br: 110.0, 76.7,
and 62.0 kcal/mol, respectively [12]. Therefore, acyl
iodides readily dissociate with formation of radicals
(Scheme 1).
Scheme 1.
In particular, the energy of formation of acetyl
radical was estimated at 5.8 0.4 kcal/mol [13]. It is
ineresting that homolytic (thermal) decomposition of
trifluoroacetyl iodide [14] yields carbon(II) oxide and
trifluoroiodomethane (Scheme 2).
Scheme 2.
Unlike readily accessible acyl chlorides, some reac-
tions of which with aprotic compounds require severe
conditions and/or the presence of a catalyst (usually
Lewis acids), acyl iodides exhibit a high reactivity.
This is explained by strong polarization of the C I
bond which readily dissociates according to both
hetero- and homolytic mechanisms. The energy of
dissociation of the C I bond in acetyl iodide is
46.0 kcal/mol, i.e., it is considerably lower than the
energies of dissociation of the C X bonds in acetyl
____________
The above data suggest wide prospects in using
acyl iodides in organic and organometallic synthesis
[10]. We previously studied reactions of acyl iodides
with alcohols [1, 2] and acyclic and cyclic ethers [3].
In continuation of these studies, in the present work
we examined reactions of acetyl iodide with mono-
and dibasic saturated, unsaturated, and aromatic acids,
namely trifluoroacetic, trichloroacetic, butyric, iso-
butyric, acrylic, benzoic, oxalic, and phthalic.
*
For preceding communications, see [1 3].
1070-4280/03/3912-1702$25.00 2003 MAIK Nauka/Interperiodica

ACYL IODIDES IN ORGANIC SYNTHESIS: IV.
1703
Aliphatic acyl chlorides react with carboxylic acids
with liberation of hydrogen chloride both in the
absence and in the presence of catalysts; these reac-
tions usually lead to formation of the corresponding
anhydrides [15] (Scheme 3).
Oxalic acid reacted with acetyl iodide to give acetic
acid, carbon(II) oxide, and molecular iodine, indicat-
ing the occurrence of exchange process. A probable
intermediate, oxalyl iodide, is extremely unstable. It
rapidly decomposes according to Scheme 6.
Scheme 3.
Scheme 6.
Exchange reaction between aliphatic acyl chlorides
and carboxylic acids is an extremely rare case. In
particular, such reaction is typical of oxalyl chloride
[15] (Scheme 4).
Phthalic acid reacts with acetyl iodide in a different
way. The products are phthalic anhydride, acetic acid,
and hydrogen iodide. This means that the exchange
process involves only one carboxylic group. Initially
formed o-iodoformylbenzoic acid undergoes intra-
molecular dehydroiodination, yielding phthalic an-
hydride (Scheme 7).
Scheme 4.
Scheme 7.
We have found no published data on reactions of
acyl iodides with carboxylic acids. Using acetyl iodide
as an example, we were the first to reveal that, unlike
acyl chlorides, acyl iodides react with monocarboxylic
acids (trifluoroacetic, trichloroacetic, butyric, iso-
butyric, acrylic, and benzoic) following exclusively
the exchange pattern (Scheme 5).
Scheme 5.
Comparison of the dissociation constants of the
examined acids (see table) shows that weak acids with
pKa values within the range from 4 to 5 react with
acetyl iodide most readily. Stronger acids, such as
trifluoro- and trichloroacetic, react with acetyl iodide
at a lower rate. This may be due to considerable elec-
tron-acceptor effect of the CX3 group (X = Cl, F),
which increases the acidity and reduces the nucleo-
philicity of the C O group. Correspondingly, (C O)
values in the IR spectra of acids RCOOH where R =
I, R = Pr; II, R = i-Pr; III, R = CH2 CH; IV, R = Ph;
V, R = CF3; VI, R = CCl3.
These reactions occur without a solvent in the
absence of an HI acceptor. In all cases, except for
trihaloacetic acids, the process is accompanied by heat
evolution which is especially strong in the reaction
with acrylic acid. The reactions of acetyl iodide with
alkanoic acids I and II and acrylic acid (III) are
almost irreversible, for the initial acetyl iodide is
more reactive than the resulting higher acyl iodides.
The reaction of acetyl iodide with benzoic acid is
reversible, so that a mixture of the initial reactants,
acetic acid, and benzoyl iodide is obtained. The reac-
tions with trifluoroacetic and trichloroacetic acids are
also reversible. In the latter cases, the equilibrium
can be displaced toward the direct reaction by removal
from the reaction mixture of the product with a lower
boiling point, trifluoroacetyl iodide or acetic acid,
respectively.
1
Me, CCl3, CF3 are 1760, 1780, and 1800 cm , re-
spectively. This series indicates increase in the C O
bond order and reduction of the electrophilicity of the
carbonyl carbon atom. Presumably, a large difference
between pK1 and pK2 of phthalic acid (2.95 and 5.41,
respectively) is responsible for its specific reaction
with acetyl iodide. Insofar as the rates of the reaction
of the latter with two carboxylic groups of phthalic
acid are different, intramolecular dehydroiodination
of labile intermediate monoiodide is faster than forma-
tion of the diodide.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

1704
VORONKOV et al.
Yields and physical constants of acyl iodides obtained by reaction of carboxylic acids RCOOH with acetyl iodide and
pKa values of the initial acids
R
Yield, %
Reaction time, h
bp C (p, mm)
n2D0
pKa (RCOOH)
Pr
79
89
86
78
9
5
5
3
5
8
8
42 43 (11)
42 45 (20)
135 140
4.81 [16]
4.86 [17]
4.26
i-Pr
CH2 CHa
1.3720
1.4200
1.637
Ph
115 118 (15)
23
4.18 [16]
0.23 [14]
0.70 [18]
CF3
CCl3
86
55 60 (2 3)
1.4470
a
Found I, %: 69.98. C3H3IO. Calculated I, %: 69.78.
We previously showed that reactions of acyl
also identified by GLC using authentic samples.
Acryloyl iodide was previously unknown.
iodides with acidic alcohols (pKa
11) occur with
liberation of HI and that alcohols with pKa 18 give
rise to the corresponding iodides RI [1]. By analogy
with weakly acidic alcohols, we presume that the reac-
tion of acetyl iodide with carboxylic acids involves
intermediate formation of acyloxonium iodide whose
subsequent transformation follows SN2 pattern, as
shown in Scheme 8.
The reaction of acetyl iodide, as well of its analogs,
with carboxylic acids may be recommended as
a simple and convenient preparative route to acyl
iodides. The procedure is advantageous, for it requires
no prelimiarily conversion of carboxylic acids into
acyl chlorides and subsequent treatment of the latter
with sodium iodide.
EXPERIMENTAL
Scheme 8.
Initial acetyl iodide was prepared by the known
procedure, i.e., by reaction of acetyl chloride with
anhydrous sodium iodide [19]. Chromatographic
analysis was performed on an LKhM-8M instrument
equipped with a thermal conductivity detector; carrier
gas helium; 2-m 4-mm column; temperature prog-
ramming mode.
Alternatively, four-membered activated complex A
can be formed as intermediate (Scheme 9).
General procedure for the synthesis of acyl
iodides. An equimolar mixture of the corresponding
monocarboxylic acid and acetyl iodide was heated at
the boiling point until the reaction was complete
(according to GLC). The resulting acetic acid and acyl
iodide were separated by fractional distillation. High-
boiling acyl iodides were distilled under reduced
pressure. A typical example is given below.
Scheme 9.
Isobutyryl iodide. A mixture of 8.5 g (0.05 mol)
of acetyl iodide and 4.4 g (0.05 mol) of isobutyric
acid was heated for 5 h at the boiling point. Distilla-
tion of the mixture gave 2.5 g (83%) of acetic acid,
bp 117 118 C [20] (identified by GLC), and 8.8 g
(89%) of isobutyryl iodide, bp 42 45 C (20 mm) [17].
The yields of acyl iodides prepared by reactions
of monocarboxylic acids with acetyl iodide and their
physical constants (boiling points and refractive
indices) are listed in table. The physical constants
were consistent with published data; the products were
Reaction of acetyl iodide with oxalic acid.
A mixture of 15 g (0.08 mol) of acetyl iodide and
4 g (0.04 mol) of oxalic acid was heated at 60 65 C
until carbon(II) oxide no longer evolved. Distillation
gave 4.9 g (92%) of acetic acid (GLC).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 12 2003

ACYL IODIDES IN ORGANIC SYNTHESIS: IV.
1705
Reaction of acetyl iodide with phthalic acid.
A mixture of 17 g (0.1 mol) of acetyl iodide and
8.2 g (0.05 mol) of phthalic acid was heated for 5 h
at 60 65 C. Distillation gave 2.7 g (92%) of acetic
acid and 7.0 g (96%) of phthalic anhydride, mp 130
131 C [20].
8. Voronkov, M.G., Dubinskaya, E.I., and Pavlov, S.F.,
Abstracts of Papers, VIIth Int. Conf. of Organometal-
lic Chemistry, Venice, 1975, p. 155.
9. Voronkov, M.G. and Dubinskaya, E.I., J. Organomet.
Chem., 1991, vol. 410, p. 1.
10. Voronkov, M.G., Vlasova, N.N., and Trukhina, A.A.,
Sovremennyi organicheskii sintez (Contemporary
Organic Synthesis), Moscow Ufa: Khimiya Reaktiv,
2003, p. 9.
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