Synthesis of 1-acetyladamantane by reaction of 1-bromoadamantane with vinyl acetate and ethylidene diacetate catalyzed by Mn2(CO)10

Article abstract of DOI:10.1134/S1070428010060084

A procedure has been developed for the synthesis of 1-acetyladamantane in 95% yield by reaction of 1-bromoadamantane with vinyl acetate or ethylidene diacetate in the presence of manganese complexes.

Full text of DOI:10.1134/S1070428010060084

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 6, pp. 820–822. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © R.I. Khusnutdinov, N.A. Shchadneva, L.F. Mukhametshina, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 6,
pp. 828–830.
Synthesis of 1-Acetyladamantane by Reaction
of 1-Bromoadamantane with Vinyl Acetate and Ethylidene
Diacetate Catalyzed by Mn (CO)
2
10
R. I. Khusnutdinov, N. A. Shchadneva, and L. F. Mukhametshina
Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bahkortostan, Russia
e-mail: ink@anrb.ru
Received November 26, 2009
Abstract—A procedure has been developed for the synthesis of 1-acetyladamantane in 95% yield by reaction
of 1-bromoadamantane with vinyl acetate or ethylidene diacetate in the presence of manganese complexes.
DOI: 10.1134/S1070428010060084
1
-Acetyladamantane is one of the key adamantane
The results characterizing the effect of the nature of
manganese compound and ligand structure on the re-
action course and the yield and composition of prod-
ucts are presented in Table 1. Complex composition of
the reaction products should be noted (run nos. 5–7,
14, 15); apart from the target compound II, the reac-
tion mixtures contained 1-adamantyl acetate (III) and
adamantan-1-ol (IV) (Scheme 1). Presumably, the
latter are formed with participation of decomposition
products of excess vinyl acetate, acetic acid, acetic
anhydride, and water [6].
derivatives that are used in the synthesis of substituted
adamantanes possessing biological activity. In partic-
ular, 1-acetyladamantane is a starting material in the
preparation of efficient anti-influenza drug Rimanta-
dine [1]. Most known methods for the preparation of
1
-acetyladamantane include a number of steps and are
based on synthetic transformations of 1-substituted
adamantanes 1-AdR (R = Br, OH, CN, COOH, COCl,
etc.) [2–4]. We previously found [5] that 1-acetylada-
mantane may be obtained by reaction of vinyl acetate
with 1,3-dibromoadamantane in the presence of
rhodium complexes; the reaction was accompanied by
evolution of hydrogen bromide. Obviously, the use of
more accessible 1-bromoadamantane (I) instead of
With a view to reduce the consumption of vinyl
acetate and minimize side processes, we tried to find
an optimal solvent. The reaction of 1-bromoadaman-
tane (I) with vinyl acetate in alcohols (methanol,
ethanol) gave adamantan-1-ol (IV) as the major prod-
uct. The yield of 1-acetyladamantane (II) in halo-
methanes (methylene chloride, chloroform, carbon
tetrachloride) was 35–45%, but the use of these sol-
vents was undesirable, for they promoted side trans-
halogenation of 1-bromoadamantane (I) with forma-
tion of less reactive 1-chloroadamantane. Among the
examined solvents, the best was acetonitrile. However,
1
,3-dibromoadamantane would be more promising
from the viewpoint of development of a simpler proce-
dure for the synthesis of 1-acetyladamantane.
Our preliminary experiments showed that effective
catalysts for the formation of 1-acetyladamantane (II)
from 1-bromoadamantane (I) and vinyl acetate may be
manganese compounds and complexes and that ethyli-
dene diacetate can also be taken as acylating agent.
Scheme 1.
Br
Ac
OAc
OH
Mn (CO)
2
10
1
55°C, 6 h
+
+
+
H C
2
OAc
I
II
III
IV
8
20

SYNTHESIS OF 1-ACETYLADAMANTANE
821
Table 1. Reaction of 1-bromoadamantane (I) with vinyl acetate (VA) in the presence of manganese compounds; molar ratio
MnX :I:VA = 1 :100:200, 155°C, 6 h
2
Product composition, %
Substrate
conversion, %
Run no.
Catalyst
Ligand
II
III
IV
oligomers
0
0
0
0
0
0
0
0
0
1
1
1
2
3
4
5
6
7
8
9
0
1
MnCl
2
–
–
–
–
–
–
–
–
15
21
18
48
56
62
60
68
32
35
00
42
70
60
85
100
100
080
060
072
045
050
080
100
100
MnBr
2
a
Mn(C17
H
35CO
2
)
2
20
40
18
37
40
b
Mn(C
7 5 2
H CO )
2
Mn(OAc)
2
10
18
10
20
Mn(acac)
Mn(acac)
2
3
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
2
2
2
2
2
2
2
2
(CO)10
(CO)10
(CO)10
(CO)10
(CO)10
(CO)10
(CO)10
(CO)10
Pyridine
2,2′-Bipyridine
Et
Morpholine
P(OPh)
PPh
Ph PCH
3
N
1
1
1
1
2
3
4
5
090
10
3
3
080
050
20
50
2
2
CH
2
PPh
2
a
Manganese stearate.
Manganese 2-ethylhexanoate.
b
2
Table 2. Reaction of 1-bromoadamantane (I) with vinyl acetate (VA) in acetonitrile in the presence of Mn (CO)10
Product composition, %
Molar ratio
(CO)10 :I:VA :MeCN
Temperature,
°C
Reaction
time, h
Substrate
conversion, %
Run no.
Mn
2
II
oligomers
1
2
3
4
5
6
7
8
1:100:100:300
1:100:200:300
1:100:200:300
1:100:200:300
1:100:200:300
1:100:300:500
2:100:300:500
2:100:300:500
100
100
120
140
150
150
150
150
6
6
6
6
6
6
3
6
018
025
047
068
085
090
095
100
100
100
100
100
100
100
090
050
10
50
in this case 2–3-fold excess of vinyl acetate was neces-
sary to attain the maximal yield of target compound II
Taking into account formation of ethylidene diacetate
from vinyl acetate during the reaction, we performed
a series of experiments aimed at elucidating the role of
ethylidene diacetate in the transformations under study.
We found that ethylidene diacetate is a more effective
(
Table 2).
The most favorable conditions included the use of
Mn (CO) (2 mol %) as catalyst and 3 equiv of vinyl
2
10
acetate. The latter was found to be rapidly converted
into ethylidene diacetate. Under these conditions, the
yield of vinyl acetate oligomers in acetonitrile at
Scheme 2.
Mn (CO)
10
OAc
2
1
55°C, 6 h
1
50°C in 3 h did not exceed 10%. Prolonged reaction
I
+
II
is undesirable because of increased yield of oligomers.
Me
OAc
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

8
22
KHUSNUTDINOV et al.
–
1
13
acylating agent than vinyl acetate. The reaction of
compound I with ethylidene diacetate in acetonitrile in
the presence of Mn (CO) at 155°C in 6 h afforded
nol). IR spectrum: ν 1720 cm (C=O). C NMR spec-
3
5
7
trum, δ , ppm: 24.30 (CH ), 27.20 (C , C , C ), 35.84
(C , C , C ), 37.43 (C , C , C ), 45.51 (C ), 212.17
(C=O).
C
3
4
6
10
2
8
9
1
2
10
9
5% of 1-acetyladamantane (II), and no by-products
were detected.
1
-Adamantyl acetate (III). Sublimes at 97°C
1
3
(
(
(
10 mm) [7]. C NMR spectrum, δ , ppm: 22.52
C
EXPERIMENTAL
3
5
7
4
6
9
CH ), 30.76 (C , C , C ), 36.17 (C , C , C ), 41.28
3
2
8
10
1
C , C , C ), 80.12 (C ), 170.19 (C=O).
The purity of the products was checked, and the
composition of the reaction mixtures was determined,
by GLC on a Khrom-5 chromatograph equipped with
a 1.2-m×3-mm column packed with 5% of SE-30 on
Chromaton N-AW-HMDS; oven temperature program-
ming from 50 to 280°C at a rate of 8 deg/min; carrier
gas helium. The IR spectra were recorded on a Specord
IR-75 spectrometer from samples dispersed in mineral
Adamantan-1-ol (IV). mp 282–283°C (sublimes);
published data [8]: mp 283–284°C (from methanol,
sublimes). C NMR spectrum, δ , ppm: 30.85 (C , C ,
C ), 36.15 (C , C , C ), 45.32 (C , C , C ), 67.90 (C ).
Mass spectrum, m/z (Irel, %): 152 (24) [M] , 109 (5), 96
(7), 95 (100), 94 (14), 79 (5), 77 (7), 55 (5), 43 (15), 41
(12), 39 (10), 29 (7).
1
3
3
5
C
2
7
4
6
10
8
9
1
+
1
3
oil. The C NMR spectra were measured from solu-
tions in CDCl on a Jeol FX 90Q instrument
This study was performed under financial support
by the Russian Foundation for Basic Research and the
Government of Bashkortostan Republic (project
no. 08-03-97 005-Povolzh’e) and by the Federal
Science and Innovation Agency of the Russian Federa-
tion (State contract no. 02.740.11.0631).
3
(
22.5 MHz); the chemical shifts were determined rela-
tive to tetramethylsilane. The mass spectra (electron
impact, 70 eV) were obtained on a Finnigan MAT-
112S instrument (ion source temperature 220°C). The
elemental compositions were determined on a Carlo
Erba 1106 analyzer.
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2
3
4
5
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0
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(
(
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1
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6
7
8
1
-Acetyladamantane (II). mp 53.2–53.5°C (from
ethanol); published data [4]: mp 54°C (from metha-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010