Acyl iodides in organic synthesis: XIII.* Reaction of acyl iodides with nitrogen-containing heteroaromatic compounds

Article abstract of DOI:10.1134/S1070428010120122

Reactions of acetyl iodide with pyridine at room temperature and with quinoline both at 20-25°C and on cooling to -50°C involve dehydrohalogenation of acetyl iodide with formation of ketene and pyridinium or quinolinium iodides. The reaction of acetyl iodide with pyridine at -5 to -50°C led to the formation of N-acetylpyridinium iodide. Benzoyl iodide reacted with both pyridine and quinoline at both -50°C and at 20-25°C to form stable N-benzoylpyridinium and N-benzoylquinolinium iodides. The reaction of pyrrole with acetyl iodide under analogous conditions was accompanied by polymerization. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010120122

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 12, pp. 1838–1842. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © M.G. Voronkov, A.V. Vlasov, N.N. Vlasova, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 12,
pp. 1827–1830.
Acyl Iodides in Organic Synthesis: XIII.* Reaction of Acyl
Iodides with Nitrogen-Containing Heteroaromatic Compounds
M. G. Voronkov, A. V. Vlasov, and N. N. Vlasova
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: Andreiwlasov@rambler.ru
Received June 2, 2008; revised November 27, 2010
Abstract—Reactions of acetyl iodide with pyridine at room temperature and with quinoline both at 20–25°C
and on cooling to –50°C involve dehydrohalogenation of acetyl iodide with formation of ketene and pyridinium
or quinolinium iodides. The reaction of acetyl iodide with pyridine at –5 to –50°C led to the formation of
N-acetylpyridinium iodide. Benzoyl iodide reacted with both pyridine and quinoline at both –50°C and at 20–
25°C to form stable N-benzoylpyridinium and N-benzoylquinolinium iodides. The reaction of pyrrole with
acetyl iodide under analogous conditions was accompanied by polymerization.
DOI: 10.1134/S1070428010120122
Published data on reactions of acyl iodides RCOI
(R = Me, Ph, etc.) with nitrogen-containing hetero-
cyclic compounds are very few in number. The synthe-
sis of 2-iodo- and 2,4-diiodopyridines by exchange
reaction of the corresponding chloro- and bromo-sub-
stituted pyridines with acetyl iodide (generated in situ
from acetyl chloride and sodium iodide) was reported.
The reaction involved intermediate formation of
1-acetyl-2-chloropyridinium iodide [2]. Likewise, ace-
tyl iodide reacted with 2-chloroquinoline to produce
2-iodoquinoline [2]. Attempts to replace in such a way
the chlorine atoms in 2,6-dichloropyridine by iodine
were unsuccessful, which was attributed to steric hin-
drances to the formation of intermediate 1-acetyl-2,6-
dichloropyridinium iodide [2]. The above scanty data
cannot represent the reactivity of acyl iodides toward
nitrogen-containing heteroaromatic compounds.
In continuation of our systematic studies on acyl
iodides as reagents and synthons in organic and
organometallic synthesis [2], in the present work we
examined reactions of acetyl and benzoyl iodides
(RCOI; R = Me, Ph) with pyridine (I), quinoline (II),
and pyrrole (III). The reactions were carried out using
equimolar amounts of the reactants both at room (20–
25°C) and reduced temperature (down to –50°C).
the formation of quaternary ammonium salts, and the
second is dehydrochlorination of MeCOCl with forma-
tion of ketene [3]. A number of attempts to obtain
products of the reaction of acetyl chloride with pyri-
dine were unsuccessful [4, 5]. N-Acetylpyridinium
chloride was synthesized by direct reaction of acetyl
chloride with pyridine in toluene, and the product was
used as analytical reagent for the determination of
alcohols and phenols [6]. By contrast, N-benzoylpyri-
dinium chloride was readily obtained by reaction of
pyridine (I) with benzoyl chloride and used as reagent
for the synthesis of benzoic anhydride as early as in the
end of the XIXth century [3].
We found that the reaction of acetyl iodide with
pyridine (I) at 20°C was accompanied by considerable
evolution of heat (the temperature rose from 20–24 to
125°C). By analogy with acetyl chloride, the process
occurred as dehydrohalogenation of acetyl iodide with
formation of ketene and pyridine hydroiodide (IV)
(Scheme 1), the latter being isolated as a solid insol-
Scheme 1.
O
+
I–
+
[H2C=C=O]
Me
I
N
N
H
I
IV
It is known that acetyl chloride reacts with tertiary
amines along two pathways. The first of these leads to
O
MeOH
[H2C=C=O]
* For communication XII, see [1].
Me
OMe
1838

ACYL IODIDES IN ORGANIC SYNTHESIS: XIII.
1839
Scheme 4.
uble in organic solvents. Ketene was identified as
methyl acetate.
O
S
OAc
S
V
+
I
+
I–
The IR spectrum of hydroiodide IV lacked absorp-
tion band typical of C=O stretching vibrations, and
absorption bands due to vibrations of the pyridine ring
were displaced toward higher frequencies (1640–
1480 cm–1 against 1590–1430 cm–1 in the IR spectrum
of initial pyridine).
Me
Me
Me
Me
A
I
S
I
AcO–
A
S
Me
–AcOH
Me
Me
B
We succeeded in synthesizing previously unknown
N-acetylpyridinium iodide (V) by reaction of acetyl
iodide with pyridine (I) at –10 to –5°C under solvent-
free conditions or in hexane at –50°C; the yields of V
were 89 and 84%, respectively (Scheme 2).
B
+
HI
S
[H2C=CH–SH]
CH3CH=S
S
25°C) to give stable N-benzoylpyridinium iodide (VI)
(Scheme 5). The reaction of pyridine with benzoyl
chloride follows a similar pattern [3].
Scheme 2.
O
–10 to –5°C
+
I–
Me
I
Scheme 5.
N
N
Ac
O
+
I–
I
V
Ph
I
N
N
N-Acetylpyridinium iodide (V) was isolated as
a yellow crystalline substance which was insoluble in
most organic solvents. Compound V at room tempera-
ture slowly decomposed into ketene and pyridine
hydroiodide (IV). Iodide V characteristically displayed
in the IR spectrum an absorption band at 1700 cm–1
due to stretching vibrations of the carbonyl group.
N-Acetylpyridinium iodide (V) vigorously reacted
with alcohols (methanol and ethanol) to give pyridine,
methyl or ethyl acetate, and HI (Scheme 3).
COPh
I
VI
We failed to obtain N-acetylquinolinium iodide by
reaction of acetyl iodide with quinoline (II). The latter
is less basic than pyridine, and in all cases (both at
room and at reduced temperature) the reaction of com-
pound II with acetyl iodide involved elimination of HI
with formation of ketene and quinoline hydroiodide
(VII) (Scheme 6), a yellow amorphous hygroscopic
substance insoluble in organic solvents. The reaction at
room temperature was accompanied by heat evolution
but was not so exothermic as with pyridine (the mix-
ture warmed up to 50–55°C). In the IR spectrum of
hydroiodide VII we observed no carbonyl absorption
band in the region of 1700 cm–1, but absorption bands
corresponding to stretching vibrations of the quinoline
ring changed their position relative to those typical of
initial quinoline (1620, 1580, 1540, and 1470 cm–1
Scheme 3.
I–
+
ROH
+ AcOR + HI
N
N
Ac
V
R = Me, Et.
Iodide V readily reacted with dimethyl sulfoxide.
The products were pyridine, acetic acid, and thioacet-
aldehyde (Scheme 4). This process may be regarded as
a version of Pummerer rearrangement [7]. Intermediate
methyl iodomethyl sulfide B loses HI, yielding thiirane
[8, 9], and the latter undergoes isomerization to thio-
acetaldehyde [9].
Scheme 6.
O
+
Me
I–
I
N
II
+
[H2C=C=O]
Elimination of hydrogen iodide from benzoyl
iodide is improbable; therefore, it reacted with pyridine
(I) both at –10 to –5°C and at room temperature (20–
N
H
VII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

VORONKOV et al.
1840
against 1600, 1590, 1570, and 1490 cm–1 in the
EXPERIMENTAL
spectrum of II).
The IR spectra were recorded from thin films on
As might be expected, benzoyl iodide reacted with
quinoline both at room and reduced temperature to
give N-benzoylquinolinium iodide (VIII) (Scheme 7).
1
13
a UR-20 spectrometer. The H and C NMR spectra
were measured on a Bruker DPX-400 spectrometer
(400 MHz for 1H) from solutions in CDCl3 using tetra-
methylsilane or hexamethyldisiloxane as internal refer-
ence. Chromatographic analysis was performed on
an HP-5890 instrument equipped with a thermal con-
ductivity detector and an Ultra-2 column, 2 m×4 mm;
injector temperature 250°C, oven temperature pro-
gramming from 70 to 280°C; carrier gas helium.
Scheme 7.
O
+
Ph
I–
I
N
II
Initial acyl iodides were prepared by reaction of the
corresponding acyl chlorides with anhydrous sodium
iodide according to the procedure described in [11].
+
[H2C=C=O]
N
COPh
VIII
Reaction of acetyl iodide with pyridine. a. Pyri-
dine, 7.9 g (0.1 mol), was added dropwise at room
temperature (22–24°C) to 17.0 g (0.1 mol) of acetyl
iodide. The mixture spontaneously warmed up to
125°C, and evolution of ketene (a greenish gas) was
observed; the latter was trapped with methanol. The
resulting methyl acetate was identified by GLC using
an authentic sample. When the reaction was complete,
the crystals were filtered off, washed with chloroform,
and evacuated under a residual pressure of 2–5 mm to
remove traces of the solvent. We isolated 16.0 g (78%)
of pyridine hydroiodide (IV). IR spectrum, ν, cm–1:
3080–3050 (C–H); 1640, 1600, 1520, 1470 (pyridine
ring); 1220, 1150, 990, 730, 670 (δCH). Found, %:
C 27.57; H 2.81; I 64.27; N 6.46. C5H6IN. Calculated,
%: C 28.98; H 2.89; I 61.36; N 6.76.
The reaction of pyrrole III with acetyl iodide both
at 20–25°C and at –10 to –5°C in the absence of
solvent resulted in polymerization of the heterocyclic
substrate (Scheme 8), as in its reactions with other
acidic reagents [10]. The resulting polymers were
black powder-like substances with an approximate
composition of [C4H5NI]n (IX). We presumed that
these reactions involved hydroiodination of pyrrole,
followed by polymerization of the hydroiodide thus
formed.
Scheme 8.
n
+
n AcI
[C4H4NH·HI]n
N
H
b. Pyridine, 7.9 g (0.1 mol), was added to 17.0 g
(0.1 mol) of acetyl iodide cooled to –10 to –5°C (using
a dry ice–acetone bath). The mixture spontaneously
warmed up to 5–10°C. The solid product was washed
with chloroform and evacuated at 20–30 mm to
remove traces of the solvent. We isolated 19.2 g of
N-acetylpyridinium iodide (V) as a yellowish amor-
phous solid with mp 170–180°C. IR spectrum, ν, cm–1:
1700 (C=O); 1610, 1590, 1520, 1470 (pyridine ring);
1140, 1010, 730, 670 (δ CH). Found, %: C 31.54;
H 2.78; I 54.22; N 5.92. C7H8INO. Calculated, %:
C 33.73; H 3.21; I 51.00; N 5.62.
III
IX
Benzoyl iodide reacted with pyrrole very vigorous-
ly both at room temperature and on cooling to –10 to
–5°C; the reaction mixtures spontaneously warmed up
to 70–115°C. In all cases, the products were black
powder-like polymers which were insoluble in water
and organic solvents. Their elemental composition was
estimated at C9–11H8–10NI1–1.5, which corresponds to
polymerization of initially formed N-benzoylpyrrolium
iodide C4H4N+HCOC6H5I–. This process is likely to be
accompanied by iodination of pyrrole, and the iodina-
tion products also undergo polymerization. The contri-
bution of the iodination process is larger in the reaction
carried out at room temperature. The elemental com-
position of the polymer obtained from pyrrole and ben-
zoyl iodide at –10°C almost coincided with that of
N-benzoylpyrrole hydroiodide, C4H4N+HCOC6H5 I–.
c. A solution of 8.5 g (0.05 mol) of acetyl iodide in
10 ml of hexane was cooled to –60 to –50°C, and 3.9 g
(0.05 mol) of pyridine was added. Removal of the sol-
vent from the reaction mixture gave 10.5 g (84%) of
N-acetyl-pyridinium iodide (V).
Reaction of N-acetylpyridinium iodide (V) with
dimethyl sulfoxide. N-Acetylpyridinium iodide (V),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

ACYL IODIDES IN ORGANIC SYNTHESIS: XIII.
1841
7.0 g (0.03 mol) was mixed with 2.2 g (0.03 mol) of
dimethyl sulfoxide, and the mixture spontaneously
warmed up to 65°C. Distillation under atmospheric
pressure gave volatile thioacetaldehyde, bp 34–36°C;
published data [12]: bp 36.9°C. IR spectrum:
1590, 1510, 1470, 1430 (aromatic rings); 1220, 1100,
1000, 900, 700, 670 (δ CH). Found, %: C 45.77;
H 3.11; I 41.28; N 4.56. C12H10INO. Calculated, %:
C 46.30; H 3.22; I 40.84; N 4.50.
Reaction of benzoyl iodide with quinoline.
Quinoline, 3.87 g (0.03 mol), was added dropwise to
6.96 g (0.03 mol) of benzoyl iodide cooled to –10°C.
The temperature of the reaction mixture did not
change. The resulting solid was washed with chloro-
form and evacuated at 20–30 mm without heating. We
isolated 8.8 g (81%) of N-benzoylquinolinium iodide
(VIII) as an amorphous substance with mp 200°C,
which was insoluble in organic solvents. IR spectrum,
ν, cm–1: 1710 (C=O); 1620, 1580, 1540, 1440, 1400
(aromatic rings); 1200, 1160, 1020, 1000, 980, 800,
690 (δ CH). Found, %: C 52.29; H 3.52; I 39.28;
N 4.16. C16H12INO. Calculated, %: C 53.18; H 3.32;
I 35.18; N 3.88.
Reaction of benzoyl iodide with pyrrole. a. Ben-
zoyl iodide, 4.15 g (0.018 mol), was added dropwise at
room temperature to 1.20 g (0.018 mol) of pyrrole, and
the mixture warmed up from 20 to 70°C. The resulting
polymeric solid was washed with chloroform and
evacuated to remove residual solvent. Found, %:
C 43.16; H 2.80, I 47.10; N 5.08. C11H10INO. Calculat-
ed, %: C 44.12; H 3.34; I 42.47; N 4.68.
1
ν 1000 cm–1 (C=S). H NMR spectrum, δ, ppm: 1.96–
1.98 d (3H, CH3), 8.5–8.9 (1H, CH=S). 13C NMR
spectrum, δC, ppm: 16.5–16.9 (CH3), 149.5 (CH=S).
The residue obtained after separation of thioacetalde-
hyde contained pyridine and acetic acid which were
identified by GLC using authentic samples.
Reaction of acetyl iodide with quinoline. a. Quin-
oline, 3.23 g (0.025 mol), was added dropwise at room
temperature to 4.25 g (0.025 mol) of acetyl iodide. The
mixture spontaneously warmed up to 50°C, and a dark
red crystalline solid separated. The precipitate was
washed with chloroform and evacuated at 20–30 mm
without heating to remove residual chloroform. We
isolated 5.1 g (80%) of quinoline hydroiodide (VII) as
a dark yellow amorphous solid insoluble in organic
solvents. IR spectrum, ν, cm–1: 1620, 1580, 1540, 1470
(quinoline ring); 1200, 1110, 790, 730 (δCH). Found,
%: H 2.62; I 49.73; N 4.26. C9H8IN. Calculated, %:
H 3.11; I 49.39; N 5.44.
b. The same amounts of the reactants were mixed
at –10°C. Yield of VII 5.3 g (83%).
b. Benzoyl iodide, 5.8 g (0.025 mol), was added to
1.68 g (0.025 mol) of pyrrole cooled to –10°C, and the
mixture warmed up to 115°C. The precipitate was dis-
solved in chloroform and the product was precipitated
with diethyl ether. The black powder-like solid was
evacuated to remove traces of diethyl ether. We isolat-
ed 4.4 g (60%) of a polymer with an approximate
composition of C11H10INO. Found, %: C 43.70;
H 3.10; I 43.49; N 5.10. C11H10INO. Calculated, %:
C 44.12; H 3.34; I 42.47; N 4.68.
Reaction of acetyl iodide with pyrrole. a. Acetyl
iodide, 6.8 g (0.04 mol), was added dropwise at room
temperature to 2.68 g (0.04 mol) of pyrrole, and the
mixture spontaneously warmed up from 24 to 51°C.
The product was a black powder insoluble in water and
organic solvents. Found, %: C 22.86; H 3.10; I 66.30;
N 6.74. C4H5IN. Calculated, %: C 24.74; H 2.57;
I 65.46; N 7.21.
b. Acetyl iodide, 6.8 g (0.04 mol), was added drop-
wise to 2.68 g (0.04 mol) of pyrrole cooled to –10°C,
and the mixture warmed up to 10°C. The resulting dark
red polymeric substance did not melt and was insol-
uble in hexane, diethyl ether, and chloroform. Found,
%: C 23.70; H 2.76; I 66.73. C4N6IN. Calculated, %:
C 24.74; H 2.57; I 65.46.
REFERENCES
1. Voronkov, M.G., Vlasova, N.N., Belousova, L.I., Grigor’-
eva, O.Yu., Tsyrendorzhieva, I.P., and Rakhlin, V.I., Russ.
J. Org. Chem., 2008, vol. 44, p. 1585.
2. Voronkov, M.G., Vlasova, N.N., and Trukhina, A.A.,
Sovremennyi organicheskii sintez (Modern Organic Syn-
thesis), Moscow: Khimiya, 2003, p. 9.
3. Sonntag, N.O.V., Chem. Rev., 1953, vol. 52, p. 237.
4. Dehn, W.M., J. Am. Chem. Soc., 1912, vol. 34, p. 1399.
5. Freudenberg, K. and Peters, D., Ber., 1919, vol. 52,
Reaction of benzoyl iodide with pyridine. Ben-
zoyl iodide, 23.2 g (0.1 mol), was added dropwise to
7.91 g (0.1 mol) of pyridine cooled to –10°C. The mix-
ture warmed up to 4°C, and the resulting solid was
washed with chloroform and evacuated to remove resi-
dual solvent. We isolated 26.5 g (85%) of N-benzoyl-
pyridinium iodide (VI) as an amorphous solid which
decomposed on heating and was insoluble in organic
solvents. IR spectrum, ν, cm–1: 1750 (C=O); 1600,
p. 1463.
6. Thompson, Q.E., J. Am. Chem. Soc., 1951, vol. 73,
p. 5841.
7. Boyle, R.E., J. Org. Chem., 1966, vol. 31, p. 3880.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

VORONKOV et al.
1842
8. Fokin, N.V. and Kolomiets, A.F., Tiirany (Thiiranes),
10. Ivanskii, V.I., Khimiya geterotsiklicheskikh soedinenii
(Chemistry of Heterocyclic Compounds), Moscow:
Vysshaya Shkola, 1978.
11. Teobald, D.W. and Smith, J.C., Chem. Ind., 1958,
vol. 32, p. 1007.
12. Reid, E.E., Organic Chemistry of Bivalent Sulfur, New
Moscow: Nauka, 1978.
9. Barret, J.K., Comprehensive Organic Chemistry,
Barton, D. and Ollis, W.D., Eds., Oxford: Pergamon,
1979, vol. 3. Translated under the title Obshchaya
organicheskaya khimiya, Moscow: Khimiya, 1985,
vol. 5, p. 163.
York: Chemical, 1960, vol. 5, chap. 2.
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