Acyl iodides in organic synthesis. Reactions with morpholine, piperidine, and N-hydrocarbylpiperidines

Article abstract of DOI:10.1134/S1070428010060047

Acyl iodides RCOI (R = Me, Ph) reacted with morpholine and piperidine to give the corresponding N-acyl derivatives and morpholine or piperidine hydroiodides. Reactions of acyl iodides with N-methyl- and N-ethylpiperidines involved cleavage of the exocyclic R-N bond with formation of N-acylpiperidine and alkyl iodide and were accompanied (to insignificant extent) by cleavage of the endocyclic N-C bond, leading to N-alkyl-N-(5-iodopentyl)acylamides. In the reaction of acetyl iodide with N-phenylpiperidine, the main process was cleavage of just endocyclic N-C bond to produce N-(5-iodopentyl)-N-phenylacetamide and its dehydroiodination product, N-(pent-4-en-1-yl)-N-phenylacetamide. Analogous reaction with benzoyl iodide afforded N-(5-iodopentyl)-N-phenylbenzamide in a poor yield.

Full text of DOI:10.1134/S1070428010060047

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 6, pp. 794–797. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © M.G. Voronkov, I.P. Tsyrendorzhieva, V.I. Rakhlin, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 6,
pp. 804–807.
Acyl Iodides in Organic Synthesis. Reactions with Morpholine,
Piperidine, and N-Hydrocarbylpiperidines
M. G. Voronkov, I. P. Tsyrendorzhieva, and V. I. Rakhlin
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: vir@irioch.irk.ru
Received November 19, 2008
Abstract—Acyl iodides RCOI (R = Me, Ph) reacted with morpholine and piperidine to give the corresponding
N-acyl derivatives and morpholine or piperidine hydroiodides. Reactions of acyl iodides with N-methyl- and
N-ethylpiperidines involved cleavage of the exocyclic R–N bond with formation of N-acylpiperidine and alkyl
iodide and were accompanied (to insignificant extent) by cleavage of the endocyclic N–C bond, leading to
N-alkyl-N-(5-iodopentyl)acylamides. In the reaction of acetyl iodide with N-phenylpiperidine, the main process
was cleavage of just endocyclic N–C bond to produce N-(5-iodopentyl)-N-phenylacetamide and its dehydro-
iodination product, N-(pent-4-en-1-yl)-N-phenylacetamide. Analogous reaction with benzoyl iodide afforded
N-(5-iodopentyl)-N-phenylbenzamide in a poor yield.
DOI: 10.1134/S1070428010060047
We previously showed [1] that acyl iodides react
with excess primary and secondary amines in a way
similar to acyl chlorides (but considerably more read-
ily) to give the corresponding carboxylic acid amides
and initial amine hydroiodides. In contrast, reactions of
acyl iodides with tertiary amines occur under mild con-
ditions in the absence of a catalyst via cleavage of N–C
bond in the amine and formation of the corresponding
N,N-disubstituted carboxylic acid amides and alkyl
iodides (Scheme 1).
Acetyl and benzoyl iodides RCOI (R = Me, Ph)
reacted with 2 equiv of morpholine or piperidine in
methylene chloride at room temperature to give the
corresponding N-acylated amines and amine hydro-
iodides (Scheme 2); analogous products were formed
in the reactions with acyclic secondary amines. It
should be noted that, unlike ethers [2], the C–O–C
fragment in morpholine molecule remained intact
under the given conditions.
Scheme 2.
Scheme 1.
O
NH
O
R3
N
O
+
2
+
R2I
X
+
R
I
R1
I
R2
R4
R1
NR3R4
O
R1 = Me, Ph; R2 = R3 = R4 = Et, Bu, CH2=CHCH2; R2 =
PhCH2 , R3 = R4 = Me; R2 = R3 = Et, R4 = Ph.
N
R
NH2
+
I–
X
X
The N–C bond in tertiary amines is cleaved by acyl
iodides most readily if one of the substituents on the
nitrogen atom is a benzyl, allyl, or alkyl group. No
cleavage of N–CPh bond was observed under these
conditions. With a view to elucidate factors responsible
for cleavage of the endocyclic N–C bond in cyclic
aliphatic amines and extend the synthetic potential of
acyl iodides, we examined their reactions with mor-
pholine, piperidine, and N-substituted piperidines.
R = Me, Ph; X = CH2, O.
The reactions of acyl iodides with N-methyl- and
N-ethylpiperidines at a molar ratio of 1:2 in methylene
chloride at room temperature involved mainly cleavage
of the exocyclic N–C bond, which is typical of their
reactions with other tertiary amines [1] (Scheme 3).
The reactions with N-methylpiperidine were accom-
794

ACYL IODIDES IN ORGANIC SYNTHESIS.
795
Scheme 3.
the reaction with benzoyl iodide was low, presumably
due to steric effect of two phenyl groups, and no
dehydroiodination was observed.
R'
O
N
+
2
R
I
Our results (Schemes 3–5) are very consistent with
those reported previously for reactions acyl iodides
with tertiary amines [1]. In both cases, quaternary am-
monium salt is formed as intermediate via addition of
acyl iodide at the nitrogen atom of N-hydrocarbyl-
piperidine. When R = Alk, the adduct decomposes with
cleavage of the exocyclic C–N bond and formation of
alkyl iodide which then reacts with excess N-alkyl-
piperidine. If R = Ph, cleavage of the endocyclic N–C
bond gives rise to 5-iodopentyl group on the nitrogen
atom, which undergoes dehydroiodination (R = Me).
O
R'
R'
N
R
N
+
I–
R = Me, Ph; R′ = Me, Et.
panied to an insignificant extent by cleavage of the
endocyclic N–C bond, leading to N-alkyl-N-(5-iodo-
pentyl) amides (yield 1.7 and 3.4% for R = Me and Ph,
respectively; Scheme 4). No analogous side process
was observed with N-ethylpiperidine.
EXPERIMENTAL
Scheme 4.
The NMR spectra were recorded on a Bruker
DPX-400 spectrometer at 400.13 MHz for H and
R'
1
O
N
100.58 MHz for 13C using CDCl3 as solvent and tetra-
methylsilane or cyclohexane as reference. The reaction
mixtures and products were analyzed by GLC on
a Tsvet-500 chromatograph equipped with a thermal
conductivity detector and a glass column, 3 m×4 mm,
packed with 10% of PSM-1000 on Inerton Super
(0.125–0.150 mm); carrier gas helium. The mass spec-
tra were obtained on a Shimadzu GCMS-QP5050A
(SPB-5ms capillary column, 60 m× 250 μm, film
thickness 0.25 μm; quadrupole mass analyzer, electron
impact, 70 eV, ion source temperature 230°C, a.m.u.
range 34–650) or LKB-2091 GC–MS instrument
(SE-54 capillary column, 38 m; ion source temperature
240°C, electron impact, 60 eV).
+
R
I
O
R
N
I
R'
Taking into account that no cleavage of N–CPh bond
occurs in reactions of acyl iodides with N,N-disub-
stituted anilines [1], we examined their reactions with
N-phenylpiperidine at a molar ratio of 1:1 in benzene
at 80°C. As might be expected, the products were the
corresponding N-(5-iodopentyl)-N-phenyl-substituted
amides which were formed as a result of cleavage of
the endocyclic N–C bond (Scheme 5). The yield was
12% (calculated on the reacted N-phenylpiperidine) for
R = Me. N-(5-Iodopentyl)-N-phenylacetamide under-
went dehydroiodination to (N-pent-4-en-1-yl)-N-phen-
ylacetamide whose yield reached 81% (on the reacted
N-phenylpiperidine). The yield of analogous product in
Initial acetyl and benzoyl iodides were synthesized
by reaction of the corresponding acyl chlorides with
anhydrous sodium iodide [3].
Reaction of acetyl iodide with morpholine.
Acetyl iodide, 0.85 g (5 mmol), was added dropwise
under stirring to a solution of 0.87 g (10 mmol) of
morpholine in 6 ml of methylene chloride. The mixture
was stirred for 9 h at room temperature, and the
precipitate was filtered off, washed with methylene
chloride, and dried under reduced pressure. Yield of
morpholine hydroiodide 0.51 g (47%). Found, %:
C 21.05; H 5.23; I 62.1; N 6.72. C4H9INO. Calculated,
%: C 22.43; H 4.21; I 59.35; N 6.54. M 214. The
filtrate was evaporated to isolate 0.52 g of a mixture
containing (according to the GC–MS data) 73% of
unreacted morpholine [mass spectrum, m/z (Irel, %): 87
(70), 71 (20), 58 (45), 43 (50)] and 27% of N-acetyl-
Scheme 5.
Ph
O
N
+
R
I
O
O
R
N
I
Ph
CH2
R
N
–HI
1
Ph
morpholine (yield 22%). H NMR spectrum, δ, ppm:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

VORONKOV et al.
796
2.07 s (3H, CH3), 3.25 m (4H, CH2O), 3.54 m (4H,
CH2N). 13C NMR spectrum, δC, ppm: 21.42 (CH3),
43.25 and 41.50 (CH2N), 65.62 (CH2O), 167.97 (C=O).
Mass spectrum, m/z (Irel, %): 129 (8) [M]+, 114 (20), 86
(70), 71 (20), 58 (45), 43 (50).
under stirring to a solution of 1.3 g (11.5 mmol) of
N-ethylpiperidine in 5 ml of methylene chloride. The
mixture was stirred for 6 h at room temperature, the
solvent was distilled off, and distillation of the residue
gave 0.49 g (72%) of N-acetylpiperidine and 0.8 g
(61%) of initial N-ethylpiperidine, bp 131°C, nD20
=
Reaction of benzoyl iodide with morpholine.
Benzoyl iodide, 1.16 g (5 mmol), was added dropwise
under stirring to a solution of 0.87 g (12 mmol) of
morpholine in 6 ml of methylene chloride. The mixture
was stirred for 6 h at room temperature, and the pre-
cipitate was filtered off, washed with methylene chlo-
ride, and dried under reduced pressure. Yield of mor-
pholine hydroiodide 0.46 g (43%). Found, %: C 23.56;
H 5.34; I 62.67; N 6.92. C8H12IN. Calculated, %:
C 22.34; H 4.65; I 59.07; N 6.51. M 214. The filtrate
was evaporated to isolate 0.68 g (71%) of N-benzoyl-
morpholine, mp 74°C; published data [4]: mp 74–
1
1.4440. H NMR spectrum, δ, ppm: 1.06 t (CH2CH3),
1.39 m (6H, CH2), 2.26 m (4H, CH2N), 2.36 q
(CH2CH3). Mass spectrum, m/z (Irel, %): 113 (25)
[M]+, 98 (100), 84 (10), 70 (7), 56 (10), 42 (30), 28
(10), 15 (3).
Reaction of acetyl iodide with N-methylpiperi-
dine. Acetyl iodide, 1.0 g (6 mmol), was added drop-
wise under stirring to a solution of 1.18 g (12 mmol) of
N-methylpiperidine in 5 ml of methylene chloride. The
mixture was stirred for 6 h at room temperature, the
solvent was distilled off, and distillation of the residue
gave 0.48 g (65%) of N-acetylpiperidine and 0.51 g
1
75°C. H NMR spectrum, δ, ppm: 3.28–3.77 m (8H,
CH2), 7.25–7.34 m (5H, Ph). 13C NMR spectrum, δC,
ppm: 42.42 and 47.26 (CH2N), 66.52 (CH2O), 127.07–
135.56 (Ph), 169.23 (C=O). Mass spectrum, m/z
(Irel, %): 191 (8) [M]+, 114 (25), 105 (78), 86 (65), 77
(65), 56 (15).
(43%) of initial N-methylpiperidine, bp 107°C, nD20
=
1.4355. 1H NMR spectrum, δ, ppm: 1.39 m (6H, CH2),
2.62 s (3H, CH3), 2.86 m (4H, CH2N). Mass spectrum,
m/z (Irel, %): 98 (10) [M – H]+, 84 (25), 70 (20), 58
(15), 42 (20), 28 (10), 15 (3). According to the GC–MS
data, the residue (1.12 g) contained 2.42% of N-(5-
iodopentyl)-N-methylacetamide. Yield 0.028 g (2%).
Mass spectrum, m/z (Irel, %): 252 (5) [M – Me]+, 211
(20), 197 (3), 126 (100), 72 (3), 56 (4), 43 (45).
Reaction of acetyl iodide with piperidine. Acetyl
iodide, 2.55 g (15 mmol), was added dropwise under
stirring to a solution of 1.3 g (15 mmol) of piperidine
in 6 ml of methylene chloride. The mixture was stirred
for 9 h at room temperature, the solvent was distilled
off, and the residue was distilled under reduced pres-
sure to isolate 0.3 g (16%) of N-acetylpiperidine,
bp 73°C (3 mm); published data [5]: bp 226°C.
1H NMR spectrum, δ, ppm: 1.68 m (2H, CH2), 2.09 s
(3H, CH3CO), 3.26 m (2H, CH2N). 13C NMR spec-
trum, δC, ppm: 21.41 (CH3CO), 25.01 (CH2), 26.2
(CH2), 47.26 (CH2N), 168.6 (C=O). Mass spectrum,
m/z (Irel, %): 127 (80) [M]+, 112 (20), 99 (10), 84
(100), 70 (40), 56 (45), 43 (50), 15 (2).
Reaction of benzoyl iodide with N-methylpiper-
idine. Benzoyl iodide, 0.78 g (34 mmol), was added
dropwise under stirring to a solution of 1.11 g
(11 mmol) of N-methylpiperidine in 5 ml of methylene
chloride. The mixture was stirred for 6 h at room tem-
perature, and the precipitate was filtered off, washed,
and dried under reduced pressure. Yield of N,N-di-
methylpiperidinium iodide 0.4 g (50%). Found, %:
C 35.07; H 6.93; I 53.94; N 6.12. C8H12IN. Calculated,
%: C 34.87; H 6.69; I 52.7; N 5.81. M 241. The solvent
was distilled off from the filtrate, and the residue was
distilled to isolate 0.53 g (84%) of N-benzoylpiperi-
dine. According to the GC–MS data, the residue
(1.25 g) contained 3.31% of N-(5-iodopentyl)-N-meth-
ylbenzamide. Yield 0.04 g (3%). Mass spectrum, m/z
(Irel, %): 238 (18), 223 (3), 204 (20), 197 (3), 148 (30),
134 (10), 119 (3), 105 (100), 77 (31), 51 (6).
Reaction of benzoyl iodide with piperidine. Ben-
zoyl iodide, 1.16 g (5 mmol), was added dropwise
under stirring to a solution of 1.0 g (12 mmol) of
piperidine in 6 ml of methylene chloride. The mixture
was stirred for 6 h at room temperature, the solvent
was distilled off, and the residue was distilled under
reduced pressure to isolate 0.8 g (85%) of N-benzoyl-
piperidine, bp 138°C (3 mm); published data [5]:
Reaction of acetyl iodide with N-phenylpiperi-
dine. Acetyl iodide, 1.86 g (11 mmol), was added
dropwise under stirring to a solution of 1.76 g
(11 mmol) of N-phenylpiperidine in 7 ml of benzene.
The mixture was stirred for 3 h at 80°C, and the sol-
vent was distilled off to isolate 1.6 g (91%) of un-
1
bp 180°C (15 mm). H NMR spectrum, δ, ppm: 3.28–
3.77 m (8H, CH2), 7.34–7.45 m (5H, Ph). Mass spec-
trum, m/z (Irel, %): 189 (33) [M]+, 188 (90) [M – H]+,
105 (80), 84 (10), 77 (35), 51 (15).
Reaction of acetyl iodide with N-ethylpiperidine.
Acetyl iodide, 0.90 g (5.3 mmol), was added dropwise
1
reacted N-phenylpiperidine. H NMR spectrum, δ,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

ACYL IODIDES IN ORGANIC SYNTHESIS.
797
ppm: 1.61–1.63 m (6H, CH2), 3.17–3.20 m (4H,
CH2N), 6.84–6.96 m and 7.25–7.27 m (5H, Ph). Mass
spectrum, m/z (Irel, %): 161 (70) [M]+, 160 (100) [M –
H]+, 146 (5), 132 (15), 120 (20), 105 (35), 91 (10), 77
(45), 51 (20). According to the GC–MS data, the resi-
due (1.25 g) contained 3.2% of N-(5-iodopentyl)-N-
phenylacetamide, yield 0.04 g (12%, calculated on the
reacted N-phenylpiperidine) {mass spectrum, m/z
(Irel, %): 331 (10) [M]+, 316 (3), 288 (5), 238 (5), 204
(15), 197 (5), 134 (31), 119 (13), 91 (20), 77 (45),
51 (6), 43 (18)}, and 14.4% of N-(pent-4-en-1-yl)-N-
phenylacetamide, yield 0.18 g (81%, calculated on the
reacted N-phenylpiperidine) {mass spectrum, m/z
(Irel, %): 203 (20) [M]+, 188 (13), 160 (100), 126 (20),
112 (80), 83 (10), 77 (30), 56 (60), 43 (45), 14 (25)}.
1.07 g (55%) of unreacted N-phenylpiperidine. Ac-
cording to the GC–MS data, the residue (1.25 g)
contained 11.3% of N-(5-iodopentyl)-N-phenylbenza-
mide. Mass spectrum, m/z (Irel, %): 393 (8) [M]+, 331
(4), 288 (3), 266 (5), 211(5), 197 (20), 180 (2), 169 (5),
155 (3), 132 (3), 105 (100), 77 (31), 51 (6).
This study was performed under financial support
by the Council for Grants at the President of the
Russian Federation (project no. NSh-255.2008.3).
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