Ritter reaction of organic nitriles with 1-bromo- and 1-hydroxyadamantanes catalyzed by manganese compounds and complexes

Article abstract of DOI:10.1134/S1070428011110042

Manganese compounds and complexes [MnCl₂, MnBr₂, Mn(OAc)₂, Mn(acac)₂, Mn(acac)₃, Mn ₂(CO)₁₀] catalyze Ritter reaction of organic nitriles with 1-bromo- and 1-hydroxyadamantanes. The reaction proceeds in water environment in the absence of acids at 100-130°C over 3-5 h and affords N-(adamantan-1-yl)amides in 75-100% yields.

Full text of DOI:10.1134/S1070428011110042

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1682−1685. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © R.I. Khusnutdinov, N.A. Shchadneva, Yu.Yu. Mayakova, L.F. Khisamova, U.M. Dzhemilev, 2011, published in Zhurnal Organicheskoi
Khimii, 2011, Vol. 47, No. 11, pp. 1650−1653
Ritter Reaction of Organic Nitriles
with 1-Bromo- and 1-Hydroxyadamantanes Catalyzed
by Manganese Compounds and Complexes
R. I. Khusnutdinov, N. A. Shchadneva, Yu. Yu. Mayakova,
L. F. Khisamova, and U. M. Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia
e-mail: ink@anrb.ru
Received February 8, 2011
Abstract—Manganese compounds and complexes [MnCl2, MnBr2, Mn(OAc)2, Mn(acac)2, Mn(acac)3, Mn2(CO)10]
catalyze Ritter reaction of organic nitriles with 1-bromo- and 1-hydroxyadamantanes. The reaction proceeds in
water environment in the absence of acids at 100–130°С over 3–5 h and affords N-(adamantan-1-yl)amides in
75–100% yields.
DOI: 10.1134/S1070428011110042
The transformations of adamantane and its derivatives
under the conditions of Ritter reaction have been fairly
wide studied since the arising N-(adamantan-1-yl)amides
are the nearest precursors of the biologically active
aminoadamantanes possessing antimicrobial and antivi-
ral activity and used in the treatment and prophylaxis of
severe diseases (influenza, herpes, pneumonia etc.) [1, 2].
1 h) at the complete conversion of 1-bromoadamantane
(I) the only reaction product was N-(adamantan-1-yl)
acetamide (IIа). Other nitriles also are actively in-
volved into the reaction: propanenitrile, benzonitrile,
4-methylbenzonitrile, acrylonitrile, malononitrile,
1,6-hexanedinitrile that under the given conditions in the
presence of Mn-containing catalysts furnish the corre-
sponding N-(adamantan-1-yl)amides IIb–IIg in 75–100%
yield. The nature and the structure of the organic nitrile do
not notably affect the selectivity and the yield of amides.
The laboratory and industrial synthesis of various
N-(adamantan-1-yl)amides using 1-bromoadamantane
(I) is most common; the generation from compound I of
adamantan-1-yl carbocation occurs under the action of
concn. sulfuric [3] and acetic acids [4], oleum [5], equi-
molar mixture of trifluoroacetic acid and boron trifluoride
etherate [6], liquid bromine [7] which are taken in a large
excess with respect to 1-bromoadamantane (I) hampering
the isolation of the target amide [8].
+ RCN + H2O
Br
I
[Mn] 3 mol%
NHCOR
IIа_IIg
100_130°C, 1_5 h
We carried out Ritter reaction of 1-bromoadamantane
(I) with acetonitrile and the other nitriles in the presence
of manganese-containing catalysts like MnCl2, MnBr2,
Mn(OAc)2, Mn(acac)2, Mn(acac)3, Mn2(CO)10 where the
best were Mn2(CO)10 and manganese(III) acetylacetonate.
The reaction proceeded in water at the molar ratio of re-
agents and catalyst [Ad-Br] : [CH3CN] : [H2O] : [Mn] =
100 : 300–500 : 100 : 1–3.
R = CH3 (a), C2H5 (b), Ph (c), 4-CH3Ph (d), CH2=CH
(e), CH2CN (f), (CH2)4CN (g).
The reaction progress was monitored by GLC. We
established the optimum reagents concentrations, the
desired conditions for the synthesis of N-(adamantan-
1-yl)amides IIa–IIg. Liquid nitriles (acetоnitrile,
Under the optimum conditions (100°С, 3 h or 130°С,
1682

RITTER REACTION OF ORGANIC NITRILES
1683
Assuming that the amidation reaction proceeded
through the stage of adamantan-1-ol (III) formation we
attempted to perform its amidation with CH3CN in the
presence of Mn-containing catalyst. However, amide IIa
did not form even under severe conditions (175°С, 45 h)
and initial adamantan-1-ol (III) was recovered intact.
We succeeded to bring alcohol III into the reaction with
acetоnitrile by activating manganese-containing catalysts
[Mn(acac)2, Mn(acac)3, Mn(OAc)2, Mn2(CO)10] with
hydrobromic acid. In the presence of the catalytic system
[Mn]–HBr adamantan-1-ol (III) reacted with acetоnitrile
in water environment at 100–120°С within 3–5 h. In the
absence of the manganese catalyst in the other identical
conditions ([1-AdОН] : [CH3CN] : [H2O] : [HBr] = 100 :
300–500 : 100 : 3) adamantan-1-ol (III) was recovered
intact. The best molar ratio of reagents was [1-AdОН] :
[CH3CN] : [H2O] : [Mn] : [HBr] = 100 : 300–500 :
100 : 3 : 3. Under the optimum conditions the yield of
N-(adamantan-1-yl)acetamide (IIa) reached 100%.
propanenitrile, benzonitrile, acrylonitrile) were used in
excess for they served the reagent and the solvent simul-
taneously. The reaction with solid nitriles (malononitrile,
4-methylbenzonitrile) was carried out in dichlorometh-
ane.
In the study of the effect of conditions on the course
of the reaction between 1-bromoadamantane (I) and
acetоnitrile in the presence of Mn-containing catalysts
in the reaction mixture at 70–80°С adamantan-1-ol (III)
was found which apparently formed by hydrolysis of
initial 1-bromoadamantane (I).
+ СH3CN + H2O
Br
I
Mn(acac)3
70°C, 3 h
+
NHCOCH3
IIa, 16%
OH
III, 84%
The other nitriles (propanenitrile, benzonitrile,
acrylonitrile, malononitrile) also showed a high activity
Experimental results of the synthesis of N-(adamantan-1-yl)acetamide from 1-bromoadamantane or adamantan-1-ol (1-AdX)
and acetоnitrile in water in the presence of manganese-containing catalysts
Molar ratio
[1-AdX] : [CH3CN] : [H2O] : [Mn] : [HBr]
Reaction
time, h
Conversion of Amide IIа
Catalyst
MnCl2
1-AdX
T, °C
1-AdX, %
yield, %
100
100
100
100
100
99
1-AdBr (I)
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdBr
1-AdOH
1-AdOH
1-AdOH
1-AdOH
1-AdOH
1-AdOH
1-AdOH
1-AdOH
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 300 : 100 : 3 : 0
100 : 500 : 100 : 1 : 0
100 : 400 : 100 : 3 : 0
100 : 500 : 100 : 3 : 1
100 : 300 : 100 : 1 : 3
100 : 300 : 100 : 1 : 3
100 : 300 : 100 : 1 : 3
100 : 300 : 100 : 3 : 3
100 : 300 : 100 : 0 : 3
130
130
130
130
110
110
110
110
110
130
100
120
120
120
120
120
100
120
120
2
2
2
1
3
3
2
3
2
1
3
6
6
6
6
6
5
5
6
82
MnCl2
85
MnBr3
89
Mn(OAc)2
Mn(OAc)2
Mn(acac)2
Mn(acac)3
Mn2(CO)10
Mn(acac)3
Mn(acac)3
Mn(acac)3
Mn(acac)3
Mn(acac)3
Mn(acac)3
Mn(acac)3
Mn(OAc)2
Mn2(CO)10
Mn2(CO)10
No catalyst
91
95
97
99
100
100
100
100
100
–
100
100
99
100
0
0
–
52
100
100
100
100
100
–
78
83
87
99
0
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

KHUSNUTDINOV et al.
1684
in the reaction with adamantan-1-ol (III) in the presence
of Mn2(CO)10–HBr.
(the ampoule was sealed), and the reaction mixture was
heated at 100°С for 5 h with stirring. On completion of
the reaction the reactor (ampoule) was cooled to room
temperature, opened, the organic layer was separated,
the reaction products were extracted from the water layer
into dichloromethane (3 × 5 ml), the solvent was distilled
off from the combined organic solutions, the residue was
recrystallized.
+ RCN + H2O
OH
III
Mn2(CO)10_HBr, 1 : 1
100_120°C, 3_5 h
Amidation of adamantan-1-ol (III) with organic
nitriles. Into a small pressure reactor of stainless steel
(V 20 ml) or in a glass ampoule (the results of parallel runs
were practically identical) under an argon atmosphere
was charged 0.3 mmol of manganese-containing catalyst,
0.3 mmol of hydrobromic acid, 10 mmol of adamantan-
1-ol (III), 20 mmol of organic nitrile, 10 mmol of water
or 2 ml of dichloromethane for solid nitriles. The reactor
was air-tight closed (the ampoule was sealed), and the
reaction mixture was heated at 100°С for 5 h with stirring.
On completion of the reaction the workup and isolation
of the products were carried out as described above.
NHCOR
IIa_IIc, IIe, IIf
R = CH3 (a), C2H5 (b), Ph (c), CH2=CH (e), CH2CN (f).
Thus Мn-containing catalysts make it possible to
carry out Ritter reaction of 1-bromoadamantane (I) and
adamantan-1-ol (III) with organic nitriles in one stage in
water without the presence of strong acids (see the table).
The structure of amides IIa–IIg was established by
spectral methods comparing the data with those of au-
thentic samples and published data.
N-(Adamantan-1-yl)acetamide (IIa). Yield 98%,
mp 147–147.5°С (methanol) {147–149°С (hexane) [9]}.
IR spectrum, ν, cm–1: 3220 (NH), 1645 (C=O), 1545
(NH). 13С NMR spectrum, δ, ppm: 25.40 (СH3), 30.85
(С3,5,7), 36.42 (С4,6,10), 41.50 (C2,8,9), 51.61 (C1), 160.86
(С=O). Mass spectrum, m/z (Irel, %): 193 [М]+ (43), 192
(9), 150 (7), 137 (8), 136 (100), 135 (24), 134 (25), 100
(8), 94 (45), 93 (18), 92 (16), 91 (17), 79 (15), 77 (14),
58 (8), 55 (7), 43 (31), 42 (12), 41 (21), 39 (14). Found,
%: С 74.61; Н 9.88; N 7.19. С12Н19NO. Calculated, %:
С 74.56; Н 9.91; N 7.25.
EXPERIMENTAL
IR spectra in the range 550–3600 cm–1 were recorded
on a spectrophotometer Bruker Vertex 70V from pel-
lets with KBr or mulls in mineral oil. 13С NMR spectra
were registered on a spectrometer Bruker Аvance-400
at operating frequency 100.62 МHz from solutions in
СDCl3. Mass spectra were taken on a GC-MS instru-
ment Shimadzu QP-2010 Plus, capillary column Supelko
PTE-5 (30 m × 0.35 mm). Elemental composition of the
reaction products was measured on an analyzer Carlo
Erba 1106.
N-(Adamantan-1-yl)propaneamide (IIb). Yield
98%, mp 104.2°С. IR spectrum, ν, cm–1: 3300 (NH), 1650
(С=О), 1550 (NH). 13С NMR spectrum, δ, ppm: 22.30
(СH3), 28.35 (СH2), 29.18 (С3,5,7), 36.12 (С4,6,10), 41.29
(C2,8,9), 51.73 (C1), 172.21 (С=O). Found, %: С 78.87;
Н 10.65; N 7.11. С13Н21NO. Calculated, %: С 79.13;
Н 10.73; N 7.10.
N-(Adamantan-1-yl)benzamide (IIc). Yield
98%, mp 148.5–149°С (hexane) (149–150°С [3]). IR
spectrum, ν, cm–1: 3440 (NH), 1655 (amide I), 1580
(С=С, aromatic), 1515 (amide II). 13С NMR spectrum, δ,
ppm: 29.51 (С3,5,7), 36.71 (С4,6,10), 41.61 (C2,8,9), 52.43
(C1), 126.80, 128.42, 130.12, 135.88 (arom), 167.09
(С=O). Found, %: С 79.82; Н 8.25; N 5.48. С17Н21NO.
Calculated, %: С 79.96; Н 8.29; N 5.48.
The reaction progress was monitored and the pu-
rity of compounds obtained was checked by GLC on
a chromatograph Chrome-5, flame-ionisation detectors,
columns 1.2 and 3 m long, diameter 3 mm; stationary
phase silicone SE-30 (5%) on the carrier Chromaton-N-
HMDS (0.125–0.160 mm), ramp from 50 to 280°С at a
rate 8 deg/min), carrier gas helium (50 ml/min).
Amidation of 1-bromoadamantane (I) with organic
nitriles. Into a small pressure reactor of stainless steel (V
20 ml) or in a glass ampoule (the results of parallel runs
were practically identical) under an argon atmosphere
was charged 0.3 mmol of manganese-containing cata-
lyst, 10 mmol of 1-bromoadamantane (I), 30 mmol of
organic nitrile, 10 mmol of water, 2 ml of dichlorometh-
ane (for solid nitriles). The reactor was air-tight closed
N-(Adamantan-1-yl)-4-methylbenzamide (IId).
Yield 75%, mp 147.5–148°С (hexane). IR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

RITTER REACTION OF ORGANIC NITRILES
1685
ν, cm–1: 3440 (NH), 1655, 1580, 1515. 13С NMR spec-
ACKNOWLEDGMENTS
trum, δ, ppm: 21.66 (СН3), 29.68 (С3,5,7), 36.07 (С4,6,10),
41.66 (C2,8,9), 52.26 (C1), 122.23, 130.03, 133.09, 142.64
(arom), 171.15 (С=O). Found, %: С 79.98; Н 8.36;
N 5.11. С18Н31NO. Calculated, %: С 80.25; Н 8.60;
N 5.20.
The study was carried out under the financial support
of the Federal agency on science and innovations (State
contract no. 02.740.11.0631).
N-(Adamantan-1-yl)acrylamide (IIe). Yield 95%,
mp 147–147.5°С (methanol) (145–147°С [9]). IR
spectrum, ν, cm–1: 3440 (NH), 1670, 1630 (С=С), 1520.
13С NMR spectrum, δ, ppm: 29.17 (С3,5,7), 36.11 (С4,6,10),
41.26 (C2,8,9), 51.75 (C1), 125.03 (=СН2), 132.07 (СН=),
164.42 (С=O). Found, %: С 75.89; Н 9.26; N 6.77.
С13Н19NO. Calculated, %: С 76.05; Н 9.33; N 6.82.
REFERENCES
1. Bagrii, E.I. Adamantany, poluchenie, svoistva, primenenie,
(Adamantans: Production, Properties, Application),
Moscow: Nauka, 1989, 264, p.
2. Gerasimova, N.P., Ermolaeva, V.V., Pashinin, A.N.,
Nozhnin, N.A., Moskvichev, Yu.A., and Alov, E.M.,
Neftekhimiya, 2005, vol. 45, p. 37.
3. Sasaki, T., Egughi, E., and Toru, T., Bull. Chem. Soc. Jpn.,
1968, vol. 41, p. 236.
4. Klimochkin, Yu.N., Bagrii, E.I., Dolgopolova, T.N., and
Moiseev, I.K., Izv. Akad. Nauk SSSR, Ser. Khim., 1988,
p. 878.
N-(Adamantan-1-yl)-2-cyanoethanamide (IIf).
Yield 85%, mp 146–146.5°С (methanol) (147–148°С
[3]). IR spectrum, ν, cm–1: 3440 (NH), 2280 (С≡N),
1690, 1530. 13С NMR spectrum, δ, ppm: 26.80 (СН2),
29.34 (С3,5,7), 36.12 (С4,6,0), 41.22 (C2,8,9), 53.28 (C1),
115.09 (СН≡N), 159.38 (С=O). Found, %: С 71.33;
Н 8.15; N 12.79. С13Н18N2O. Calculated, %: С 71.52;
Н 8.31; N 12.83.
5. Butenko, L.N. and Khardin, A.P., USSR Inventor’s
Certificate 491616, 1976.
6. Plakhotnik, V.M., Kovtun, V.Yu., andYashunskii, V.G., Zh.
Org. Khim., 1982, vol. 18, p. 1001.
7. Baklan, V.F., Khil’chevskii, A.N., and Kukhar’, V.P., Zh.
Org. Khim., 1984, vol. 20, p. 2238.
8. Moiseev, I.K., Makarova, N.V., and Zemtsova, M.N., Usp.
Khim., 1999, vol. 68, p. 1102.
9. Shokova, E., Mousoulou, T., Luzikov, Y., and Kovalev, V.,
Synthesis, 1997, p. 1034.
N-(Adamantane-1-yl)-5-cyanopentanamide (IIg).
Yield 78%, mp 199–200°С (methanol). IR spectrum, ν,
cm–1: 3260 (NH), 2240 (С≡N), 1650, 1560. 13С NMR
spectrum, δ, ppm: 15.68 (СН2), 24.15 (СН2), 29.51
(С3,5,7), 36.28 (СН2), 36.71 (С4,6,10), 41.61 (C2,8,9), 54.70
(C1), 114.54 (СН≡N), 171.71 (С=O). Found, %: С 73.56;
Н 9.18; N 10.74. С16Н24N2O. Calculated, %: С 73.80;
Н 9.29; N 10.76.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011