Acyl iodides in organic synthesis. Reactions of acetyl iodide with urea, thiourea, and their N,N′-disubstituted derivatives

Article abstract of DOI:10.1134/S1070428009040022

Acetyl iodide reacted with urea and its derivatives to give the corresponding N-substituted products. The reactions of acetyl iodide with thiourea, N,N′-dimethylthiourea, imidazolidine-2-thione, and hexahydropyrimidine-2-thione resulted in the formation o

Full text of DOI:10.1134/S1070428009040022

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 486–490. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © M.G. Voronkov, N.N. Vlasova, O.Yu. Grigor’eva, L.I. Belousova, A.V. Vlasov, 2009, published in Zhurnal Organicheskoi Khimii,
2009, Vol. 45, No. 4, pp. 501–505.
Acyl Iodides in Organic Synthesis.
Reactions of Acetyl Iodide with Urea, Thiourea,
and Their N,N′-Disubstituted Derivatives
M. G. Voronkov, N. N. Vlasova, O. Yu. Grigor’eva, L. I. Belousova, and A. V. Vlasov
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: grigoreva_o@irioch.irk.ru
Received May 8, 2008
Abstract—Acetyl iodide reacted with urea and its derivatives to give the corresponding N-substituted prod-
ucts. The reactions of acetyl iodide with thiourea, N,N′-dimethylthiourea, imidazolidine-2-thione, and hexa-
hydropyrimidine-2-thione resulted in the formation of S- or N-acetyl derivatives, depending on the temperature
and structure of the sulfur functionality (thione or thiol). By contrast, in the reaction of acetyl iodide with
N,N′-bis(3-triethoxysilylpropyl)thiourea one ethoxy group on the silicon atom was replaced by iodine with
formation of N-{3-[(diethoxy)iodosilyl]propyl}-N′-[3-(triethoxysilyl)propyl]thiourea. The latter decomposed on
heating to give 3-triethoxysilylpropyl isothiocyanate and silicon-containing polymer with the composition
C45H97IN6O14.5S3Si6.
DOI: 10.1134/S1070428009040022
It is known that acyl chlorides react with urea and
its derivatives to give the corresponding N-acyl-substi-
tuted ureas (ureides) [1]. Reactions of acyl chlorides
with thiourea and its derivatives lead to the formation
of S- or N-acyl-substituted products, depending on the
temperature. S-Acyl derivatives are formed at lower
temperature, and they usually undergo thermal rear-
rangement into N-acyl isomers (acylation products of
thiourea at elevated temperature) [2].
products were the corresponding N-acetyl derivatives I
and II (yield 85 and 65%, respectively; Scheme 1).
Scheme 1.
X
O
X
O
+
–HI
H2N
NH2
Me
I
H2N
N
H
Me
I, II
I, X = O; II, X = S.
While continuing our systematic studies on the use
of the simplest acyl iodides RCOI (R = Me, Ph) as
synthons and reagents in organic and organometallic
synthesis [3], we were the first to examine reactions of
acetyl iodide with urea, thiourea, and some their
N,N′-disubstituted derivatives such as imidazolidin-
2-one, hexahydropyrimidin-2-one, N,N′-dimethylthio-
urea, imidazolidine-2-thione, 3,4,5,6-tetrahydropyrim-
idine-2-thiol, and N,N′-bis(3-triethoxysilylpropyl)-
thiourea.
Exothermic character of the reaction is responsible
for the formation from thiourea of compound II rather
than of the corresponding isothiuronium salt [4]. When
the reaction was performed on cooling (–5 to 0°C), the
expected S-acetyl derivative, S-acetylisothiuronium
iodide (III), was obtained (Scheme 2).
Scheme 2.
S
O
NH2
O
–5 to 0°C
–HI
+
I–
We found that acetyl iodide reacted with urea and
thiourea at a molar ratio of 1:1 in a way similar to acyl
chloride but, unlike the latter, in the absence of a cata-
lyst (sulfuric acid) [1]. The reactions at room tempera-
ture were accompanied by heat evolution, and the
H2N
NH2
Me
I
H2N
S
Me
III
Isothiuronium salt, namely S-acetyl-N,N′-dimethyl-
isothiuronium iodide (IV), was isolated as the only
486

ACYL IODIDES IN ORGANIC SYNTHESIS.
487
product in the reaction of acetyl iodide with N,N′-di-
methylthiourea (Scheme 3).
The same compound was obtained in 88% yield in
the reaction of imidazolidine-2-thione with 2 equiv of
acetyl iodide under analogous conditions.
Scheme 3.
Treatment of imidazolidine-2-thione with 2 equiv
of acetyl iodide at 50–60°C resulted in the formation
of a mixture of two products, one of which was iso-
meric to VII. It was assigned the structure of imid-
azolidine-2-thione hydroiodide (VIII). The second
product was 1,3-diacetylimidazolidine-2-thione dihy-
droiodide (IX) (Scheme 7).
S
O
+
Me
Me
Me
N
N
H
Me
S
I
H
NH
O
I–
Me
N
H
Me
IV
Scheme 7.
Exothermic reactions of acetyl iodide with imid-
azolidin-2-one at ratios of 1:1 and 2:1 afforded crys-
talline 1-acetylimidazolidin-2-one hydroiodide (V) and
1,3-diacetylimidazolidin-2-one dihydroiodide (VI), re-
spectively (Schemes 4, 5).
O
HN
NH
HN
NH2
+
2
I–
Me
I
S
S
VIII
H
H
Scheme 4.
N
N
Me
Me
+
2I–
O
H
O
O
O
S
HN
NH
HN
N
Me
+
I–
IX
Me
I
O
O
V
The reactions of acetyl iodide with hexahydro-
pyrimidin-2-one and 3,4,5,6-tetrahydropyrimidine-2-
thione at a molar ratio of 2:1 gave the corresponding
1,3-diacetylpyrimidine dihydroiodides X and XI
(Schemes 8, 9). Dihydroiodide XI was formed as the
Scheme 5.
O
HN
NH
+
2
Me
I
O
Scheme 8.
H
H
O
Me
N
N
Me
2I–
O
HN
NH
+
2
O
O
Me
I
VI
O
Unlike imidazolidin-2-one, the reactions of acetyl
iodide with imidazolidine-2-thione were not accom-
panied by heat evolution, indicating lower reactivity of
the thiourea derivative as compared to its oxygen-con-
taining analog. When the reaction of acetyl iodide with
imidazolidine-2-thione was carried out in diethyl ether,
the product was 2-sulfanyl-4,5-dihydro-1H-imidazole
hydroiodide (VII, yield 86%; Scheme 6). This is the
first example of dehydroiodination of acetyl iodide by
the action of a base containing a thioxo group.
H
H
2I–
Me
Me
N
N
O
O
O
X
Scheme 9.
O
HN
NH
+
2
Me
I
S
Scheme 6.
H
O
HN
NH
HN
NH
+
I–
2I–
Me
Me
N
N
Me
I
S
SH
VII
O
SH
O
XI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

VORONKOV et al.
Scheme 10.
MeCOI
488
S
S
EtO
(EtO)3Si
N
N
H
Si(OEt)3
Si
I
N
H
N
Si(OEt)3
–EtOAc
H
H
EtO
XII
EtO
EtO
Si
I
NH2
+
+
(EtO)3Si
(EtO)3Si
NCS
XIII
XV
XIV
XVI
EtO
EtO
Si
I
NCS
NH2
(EtO)3Si
NCS
(EtO)3Si
SCN
Scheme 11.
S
S
EtO
Si
OEt
O
n XII
(EtO)3Si
N
N
Si
N
H
N
–nEtI
H
H
H
OEt OEt
n
XVII
only product in the reactions performed both at 50–
60°C under solvent-free conditions and in diethyl ether
at 20–24°C. The observed difference in the reactivity
of cyclic thiourea derivatives is likely to be determined
by the nature of the sulfur functionality (C=S and
C–SH groups) [4].
XVI (Scheme 10) resulting from decomposition of
XII. This process involves cleavage of the C–O bond
in the SiOAlk moiety, which is typical of iodosilanes,
and formation of Si–O–Si bond [6, 7] and is respon-
sible for the appearance of ethyl iodide in the reaction
mixture.
On the other hand, polymer XVII contained 9–10%
of iodine, while no 3-triethoxysilylpropylamine (XV)
was detected among decomposition products of com-
pound XII. Presumably, the reason is that amine XV
reacts with ethyl iodide to give quaternary ammonium
salt (EtO)3Si(CH2)3N+H2Et·I– (XVIII) which is also
involved in condensation processes.
The reaction of acetyl iodide with N,N′-bis(3-tri-
ethoxysilylpropyl)thiourea followed a quite different
path. By analogy with the reaction of MeCOI with
alkyl(alkoxy)silanes, studied by us previously [5], in
the first step one ethoxy group on the silicon atom is
replaced by iodine with formation of N-{3-[diethoxy-
(iodo)silyl]propyl}-N′-[3-(triethoxysilyl)propyl]thio-
urea (XII) and ethyl acetate (Scheme 10). Upon at-
tempted vacuum distillation compound XII underwent
partial decomposition to produce 3-triethoxysilyl-
propyl isothiocyanate (XIII) which, according to the
IR data, contained an impurity of isomeric 3-trieth-
oxysilylpropyl thiocyanate and was converted into
rubber-like organosilicon polymer of the composition
C45H97IN6O14.5S3Si6 (XVII) (Scheme 11). Polymer
XVII is insoluble, but it swells in organic solvents. Its
IR spectrum indicated the presence of S=C=N,
S–C≡N, and Si–O–Si fragments. Ethyl acetate and
ethyl iodide were detected in the reaction mixture by
gas chromatography–mass spectrometry. Obviously,
polymer XVII is formed via polymerization of iodide
XII, as well as via condensation of iodides XIV and
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer from samples prepared as thin films. Gas
chromatographic–mass spectrometric analysis was
performed on an HP-5890 gas chromatograph coupled
with an HP 5971A mass-selective detector (electron
impact, 70 eV; Ultra-2 column, stationary phase 5% of
phenylmethylsilicone; injector temperature 250°C,
oven temperature programming from 70 to 280°C at
a rate of 20 deg/min).
Acetyl iodide was prepared by reaction of anhy-
drous sodium iodide with acetyl chloride according to
the procedure described in [8].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

ACYL IODIDES IN ORGANIC SYNTHESIS.
489
Reaction of acetyl iodide with urea. Acetyl
iodide, 8.5 g (50 mmol), was slowly added to 3.0 g
(50 mmol) of urea. The mixture warmed up, and
evolution of hydrogen iodide was observed. The mix-
ture was kept for 2 h at 55–60°C, and the precipitate
was filtered off, recrystallized from ethanol, and sub-
limed under reduced pressure. We thus isolated 9.8 g
(85%) of N-acetylurea (I) with mp 175–177°C; pub-
lished data [9]: mp 218–219°C [9]. Found, %: C 35.06;
H 6.29; N 27.12. C3H6N2O2. Calculated, %: C 35.29;
H 5.88; N 27.45.
published data [9]: mp 165–166°C. IR spectrum, ν,
cm–1: 1700 (C=O); 1600, 1540 (δNH); 1240 (C–N);
1040 (C=S). Found, %: C 30.24; H 5.09; N 22.99;
S 25.22. C3H6IN2OS. Calculated, %: C 30.50; H 5.08;
N 23.72; S 27.11.
b. Acetyl iodide, 8.5 g (50 mmol), was added on
cooling to 3.8 g (50 mmol) of thiourea, and the mixture
was kept for 3 h at –5 to 0°C. The precipitate was
washed with diethyl ether. Yield of S-acetylisothiuro-
nium iodide (III) 11.3 g (91%), mp 84–85°C. IR spec-
trum, ν, cm–1: 1700 (C=O); 1600 (δ NH); 1580
(δ+NH3). Found, %: C 14.59; H 2.83; I 51.20; N 11.21;
S 13.40. C3H7IN2OS. Calculated, %: C 14.63; H 2.80;
I 51.62; N 11.38; S 13.00.
Reaction of acetyl iodide with imidazolidin-
2-one. a. Acetyl iodide, 4.25 g (25 mmol), was added
to 2.15 g (25 mmol) of imidazolidin-2-one. The mix-
ture warmed up to 50–60°C and was left to stand for
24 h at room temperature. The resulting crystalline
material was kept for 1 h under reduced pressure (2–
3 mm) to remove volatile impurities. The residue was
6.1 g (95%) of 1-acetylimidazolidin-2-one hydroiodide
(V), mp 75–76°C. IR spectrum, ν, cm–1: 1750
(1-C=O), 1650 (C2=O), 600 (I–). Found, %: C 24.51;
H 3.54; I 42.56. C5H9IN2O2. Calculated, %: C 23.46;
H 3.54; I 49.56.
Reaction of acetyl iodide with N,N′-dimethyl-
thiourea. Acetyl iodide, 8.5 g (50 mmol), was added
to 5.2 g (50 mmol) of N,N′-dimethylthiourea, and the
mixture was kept for 5.5 h at room temperature.
Recrystallization from ethanol gave 9.3 g (68%) of
S-acetyl-N,N′-dimethylisothiuronium iodide (IV) as
brown crystals with mp 105°C. IR spectrum, ν, cm–1:
3370 (NH); 1630 (C=N); 1515 (δ+NH); 1490 (δNH);
1230, 1180 (C–N). Found, %: C 21.38; H 2.99;
I 56.58; N 8.66; S 10.75. C5H11IN2OS. Calculated, %:
C 21.89; H 4.01; I 46.35; N 10.21; S 11.68.
b. Imidazolidin-2-one, 4.3 g (50 mmol), was mixed
with acetyl iodide, 17.0 g (100 mmol), and the mixture
sharply warmed up to 60–65°C. It was left to stand for
24 h and was then evacuated at a residual pressure of
1–2 mm to obtain 20.0 g (94%) of 1,3-diacetylimidaz-
olidin-2-one dihydroiodide (VI) as black crystals with
mp 104–105°C. IR spectrum, ν, cm–1: 1750 (1-C=O,
3-C=O), 1680 (C2=O), 600 (I–). Found, %: C 20.09;
H 2.84; I 57.88; N 7.37. C7H12I2N2O3. Calculated, %:
C 19.74; H 2.84; I 59.58; N 6.58.
Reaction of acetyl iodide with imidazolidine-2-
thione. a. Acetyl iodide, 8.5 g (50 mmol), was added
under stirring to a mixture of 5.1 g (50 mmol) of
imidazolidine-2-thione and 10 ml of diethyl ether, and
the mixture was heated for 6 h under reflux. The pre-
cipitate was filtered off, washed with diethyl ether, and
kept for 1 h under reduced pressure (3 mm) to remove
traces of the solvent. Yield of 4,5-dihydroimidazole-
2-thiol hydroiodide (VII) 11.7 g (86%), mp 72–73°C.
IR spectrum, ν, cm–1: 3330 (CH), 1690 (C=N), 1460
(δNH). Found, %: C 15.55; H 2.95; I 55.07; N 11.86;
S 13.11. C3H7IN2S. Calculated, %: C 15.65; H 3.04;
I 55.21; N 12.17; S 13.91.
Reaction of acetyl iodide with hexahydropyrim-
idin-2-one. A mixture of 2.5 g (25 mmol) of hexahy-
dropyrimidin-2-one and 8.5 g (50 mmol) of acetyl
iodide was heated for 1 h at 50–60°C. The resulting
thick black undistillable material was kept at a residual
pressure of 1–2 mm at room temperature to remove
volatile impurities. We thus obtained 11.0 g (100%) of
tarry 1,3-diacetylhexahydropyrimidin-2-one dihydro-
iodide (X). IR spectrum, ν, cm–1: 1740 (1-C=O,
3-C=O), 1620 (C2=O), 580 (I–). Found, %: C 22.67;
H 4.00; I 57.35; N 7.89. C8H14I2N2O3. Calculated, %:
C 21.84; H 3.21; I 57.68; N 6.38.
b. Under analogous conditions, the reaction of
2.55 g (25 mmol) of imidazolidine-2-thione with 8.5 g
(50 mmol) of acetyl iodide gave 9.8 g (88%) of com-
pound VII, mp 72–74°C. IR spectrum, ν, cm–1: 3330
(CH), 1690 (C=N), 1460 (δNH). Found, %: C 15.38;
H 3.41; I 57.09; N 12.02; S 13.30. C3H7IN2S. Calculat-
ed, %: C 15.65; H 3.04; I 55.21; N 12.17; S 13.91.
Reaction of acetyl iodide with thiourea. a. Acetyl
iodide, 8.5 g (50 mmol), was added to 3.8 g (50 mmol)
of thiourea, and the mixture was kept for 3 h at 50–
60°C. Recrystallization of the precipitate from ethanol
gave 7.8 g (64%) of N-acetylthiourea (II), mp 167°C;
c. Acetyl iodide, 8.5 g (50 mmol), was added under
stirring to 2.55 g (25 mmol) of imidazolidine-2-thione,
and the mixture was kept for 5.5 h at 55–60°C. When
the reaction was complete, crystal deposited on the
walls of the flask were collected and washed with
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

VORONKOV et al.
490
diethyl ether. Yield of imidazolidine-2-thione hydro-
iodide (VIII) 2.1 g (19%), mp 115–118°C. IR spec-
trum, ν, cm–1: 3330 (CH); 2650 (+NH), 1690 (C=N+),
1438 (δNH), 1300 (C–N), 1200 (C=S). Found, %:
C 16.40; H 3.19; I 56.32; N 11.64; S 12.80. C3H7IN2S.
Calculated, %: C 15.65; H 3.04; I 55.21; N 12.17;
S 13.91. The precipitate was washed with diethyl ether
and evacuated to remove traces of diethyl ether and
volatile impurities. Yield of 1,3-diacetylimidazolidine-
2-thione dihydroiodide (IX) 8.7 g (78%), mp 129–
130°C. Found, %: C 18.27; H 2.09; I 52.68; N 6.65;
S 7.76. C5H9I2N2O2S. Calculated, %: C 19.00; H 2.71;
I 57.46; N 7.24; S 7.24.
129°C (2 mm), nD20 = 1.4679. IR spectrum, ν, cm–1:
2970–2880 (CH), 2160–2070 (SC≡N, N=C=S), 1070
(SiOC). Found, %: C 45.18; H 7.58; N 5.11; S 11.72;
Si 8.43. C10H21NO3SSi. Calculated, %: C 45.62;
H 7.98; N 5.32; S 12.16; Si 10.64; and 4.7 g (56%) of
organosilicon polimer XVII. IR spectrum, ν, cm–1:
2180–2050 (N=S=C, SC≡N), 1100–1020 (SiOSi).
Found, %: C 40.13; H 6.76; I 9.40; N 7.23; S 7.94;
Si 13.79. C45H97IN6O14.5S3Si6. Calculated, %: C 40.17;
H 7.21; I 9.44; N 6.25; S 7.14; Si 12.54. According to
the GC–MS data, volatile fraction, 2.0 g (24%), con-
tained ethyl acetate and ethyl iodide. Mass spectrum,
m/z (Irel, %): 156 (38) [M1]+, 127 (31), 88 (21) [M2]+,
43 (10).
Reaction of acetyl iodide with 3,4,5,6-tetrahydro-
pyrimidine-2-thione. a. Acetyl iodide, 8.5 g
(50 mmol), was added to 2.9 g (25 mmol) of 3,4,5,6-
tetrahydropyrimidine-2-thione. The mixture slightly
warmed up and was kept for 5 h at 50–60°C. The crys-
talline product was washed with diethyl ether and
evacuated at a residual pressure of 2–3 mm to remove
traces of diethyl ether and volatile impurities. Yield of
1,3-diacetyl-3,4,5,6-tetrahydropyrimidine-2-thiol dihy-
droiodide (XI) 10.9 g (96%). Brown crystals, mp 115–
117°C. IR spectrum, ν, cm–1: 3220 (CH); 2970 (+NH),
2629 (SH), 1744 (C=O), 1652 (C=N+), 1570 (δNH+).
Found, %: C 20.37; H 3.19; I 57.74; N 6.24; S 7.28.
C8H14I2N2O2S. Calculated, %: C 21.05; H 3.07;
I 55.70; N 6.14; S 7.01.
This study was performed under financial support
by the Council for Grants at the President of the
Russian Federation, Program for Support of Leading
Scientific Schools (project no. NSh-255.2008.3).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009