Alkylation of dicarbonyl compounds with 1-bromoadamantane in the presence of metal complex catalysts

Article abstract of DOI:10.1134/S1070428016030064

Adamantyl-substituted dicarbonyl compounds have been synthesized by reactions of 1-bromo-adamantane with ethyl acetoacetate, 1,3-diphenylpropane-1,3-dione, and dimethyl malonate in the presence of iron and manganese complexes.

Full text of DOI:10.1134/S1070428016030064

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 3, pp. 329–331. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © R.I. Khusnutdinov, N.A. Shchadneva, L.F. Khisamova, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 3,
pp. 350–352.
Alkylation of Dicarbonyl Compounds with 1-Bromoadamantane
in the Presence of Metal Complex Catalysts
R. I. Khusnutdinov, N. A. Shchadneva, and L. F. Khisamova
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: inklab4@gmail.com
Received September 30, 2015
Abstract—Adamantyl-substituted dicarbonyl compounds have been synthesized by reactions of 1-bromo-
adamantane with ethyl acetoacetate, 1,3-diphenylpropane-1,3-dione, and dimethyl malonate in the presence of
iron and manganese complexes.
DOI: 10.1134/S1070428016030064
Adamantyl-substituted dicarbonyl compounds are
important adamantane derivatives. They attract interest
as starting materials for the synthesis of nitrogen het-
erocycles possessing high biological activity [1]. The
most common methods for the synthesis of adamantyl-
substituted β-dicarbonyl compounds are based on their
reaction with adamantan-1-ol [2–7]. Adamantylation of
dicarbonyl compounds is carried out in the presence of
Lewis acids such as Sc(OTf)3, Ga(OTf)3, In(OTf)3, or
Cu(OTf)3 [2, 3]. Another method is based on the ex-
change reaction of 1-bromoadamantane with metal
acetylacetonates: Co(acac)2, Cu(acac)2, and Pd(acac)2
[4, 5]. 2-Adamantyl-substituted diethyl malonate was
prepared by acylation of diethyl malonate with ada-
mantane-1-carbonyl chloride and (adamantan-1-yl)-
acetyl chloride [6, 7]. However, these procedures are
characterized by low yields, while the exchange
reaction requires stoichiometric amount of the metal
complex [4, 5].
The goal of the present study was to find new ef-
ficient metal complex catalysts for the adamantylation
of β-dicarbonyl compounds with 1-bromoadamantane.
1-Bromoadamantane (1) reacted with ethyl aceto-
acetate (2) in the presence of Fe(acac)3 to give ethyl
2-(adamantan-1-yl)-3-oxobutanoate (3) at 150°C
(Scheme 1). The reaction was complete in 20 min.
Prolonged reaction time affected neither the conver-
sion of 1 nor the yield of 3. Ethyl acetoacetate (2) was
taken in excess since it simultaneously acted as reagent
and solvent. Taking into account that the initial com-
pounds are solids, analogous reaction of 1 with 1,3-di-
phenylpropane-1,3-dione (4) was carried out in diethyl
ether in a sealed ampule (Scheme 2; see table). No
reaction was observed in other solvents (hexane,
Scheme 1.
O
O
O
150°C, 20 min
+
Me
Conversion 90%
Me
OEt
Br
O
OEt
O
1
2
3
O
O
Et2O, 150°C, 3 h
Conversion 85%
+
Ph
Ph
Ph
Br
O
Ph
1
4
5
329

KHUSNUTDINOV et al.
330
Scheme 2.
O
Mn(acac)3, 130°C, 3 h
Conversion 61%
OMe
OMe
O
O
O
7
+
MeO
OMe
Br
Mn(acac)3, 160°C, 3 h
Conversion 85%
1
6
OMe
+
OMe
O
O
8
9
chloroform, DMF, DMSO). Prolonged heating resulted
in tarring. Such metal complexes as Rh(PPh3)3Cl,
Pd(PPh3)2Cl2, Mo(CO)6, and Cr(CO)6 were inactive in
this reaction.
EXPERIMENTAL
The IR spectra were recorded in KBr or mineral oil
1
13
on a Bruker Vertex 79V spectrometer. The H and C
NMR spectra were measured from solutions in CDCl3
on a Bruker Avance-400 spectrometer at 400.13 and
100.62 MHz, respectively, relative to tetramethyl-
silane. The mass spectra were obtained on a Shimadzu
GCMS-QP2010Plus instrument (SPB-5 capillary col-
umn, 30 m×0.25 mm; carrier gas helium; oven tem-
perature programming from 40 to 300°C at a rate of
8 deg/min; injector temperature 280°C; ion source
temperature 200°C; electron impact, 70 eV). The ele-
mental compositions were determined on a Carlo Erba
1106 analyzer.
An important adamantane derivative is dimethyl
2-(adamantan-1-yl)malonate (7). It is used as precursor
to adamantane-containing C11–C12 esters that are ef-
ficient friction modifiers due to their ability to form
thin protecting films on a metal surface [8]. The reac-
tion of 1 with dimethyl malonate was catalyzed by
Mn(acac)3, and its direction depended on the tempera-
ture. Compound 7 was formed in 3 h at 130°C at
a 1:6:Mn(acac)3 ratio of 100:100:(1–3). Raising the
temperature to 160°C led to the formation of a mixture
of methyl 3-(adamantan-1-yl)-3-oxopropanoate
(8, 48%) and 1-methoxyadamantane (9, 34%). Di-
methyl malonate was taken in excess to ensure reac-
tion medium.
The progress of reactions, purity of products, and
compositions of reaction mixtures were monitored by
GLC on a Chrom-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
The structure of the isolated compounds was deter-
mined by spectral methods, as well as by comparing
with authentic samples and published data [2].
Yields of 2-(adamantan-1-yl)-1,3-diphenylpropane-1,3-dione (5) in the reaction of 1,3-diphenylpropane-1,3-dione (4) with
1-bromoadamantane in diethyl ether, catalyzed by metal complexes
Catalyst
Fe(acac)3
Molar ratio catalyst:1:4
Temperature, °C
Reaction time, h
Yield of 5, %
3:100:100
3:100:100
3:100:100
5:100:100
5:100:100
3:100:100
3:100:100
3:100:100
150
180
160
180
160
100
150
100
3
1
3
1
3
6
3
6
79
64
75
72
73
28
36
24
Fe(acac)3
Mn(acac)3
Mn(acac)3
Fe(acac)2
Fe(acac)3 + Et3Na
Fe(acac)3 + Et3N
a
Fe(acac)3
a
In 1,4-dioxane.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

ALKYLATION OF DICARBONYL COMPOUNDS WITH 1-BROMOADAMANTANE
331
gas helium. All initial compounds were commercial
products (from Acros Organics) with a purity of no
less than 99%.
ppm: 1.59 (6H, CH2), 1.90 s (6H, CH2), 2.06 s (3H,
CH), 3.31 s (1H, CH), 3.64 s (6H, OCH3). 13C NMR
spectrum, δC, ppm: 28.50 (CH), 36.45 (CH2), 39.91
(CH2), 40.24 (CH2), 41.01 (CH2), 42.62 (C1), 49.20
(OCH3), 52.35 (CH), 167.09 (C=O). Mass spectrum,
m/z (Irel, %): 233 (67), 215(9), 191 (50), 173 (3), 149
(4.5), 135 (35), 133 (43), 117 (24), 105 (16), 91 (35),
79 (14), 43 (100). Found, %: C 67.91; H 8.98.
C15H22O4. Calculated, %: C 67.64; H 8.33. M 266.33.
General procedure for the alkylation of dicar-
bonyl compounds with 1-bromoadamantane. The
reactions were carried out in a 20-mL glass ampule or
a 17-mL stainless-steel high-pressure microreactor
(the results of parallel runs almost did not differ).
An ampule (microreactor) was charged under argon
with 0.3 mmol Fe(acac)3, 10 mmol of 1-bromoada-
mantane (1), and 10–15 mmol of β-dicarbonyl com-
pound. The ampule was sealed (the reactor was
hermetically closed) and heated for 0.3–3 h at 150–
170°C. When the reaction was complete, the ampule
(reactor) was cooled to room temperature and opened,
the solvent was distilled off, and the residue was
purified by column chromatography on silica gel using
hexane–ethyl acetate as eluent. Given below are
isolated yields.
Methyl 3-(adamantan-1-yl)-3-oxopropanoate (8).
Yield 48%, bp 176–178°C (10 mm). IR spectrum, ν,
cm–1: 2910, 2851 (C–H); 1737, 1693 (C=O). 13C NMR
spectrum, δC, ppm: 30.73 (CH), 39.91 (CH2), 40.24
(CH2), 42.62 (CH2), 49.20 (C1), 52.35 (CH3), 167.14
(C=O), 204.52 (C=O). Mass spectrum, m/z (Irel, %):
192 (11), 149 (4.8), 135 (100), 117 (12), 92 (15), 79
(12), 43 (34). Found, %: C 71.71; H 8.98. C14H20O3.
Calculated, %: C 71.16; H 8.53. M 236.3.
1-Methoxyadamantane (9). Yield 34%, bp 67–
68°C (3 mm). 13C NMR spectrum, δC, ppm: 32.62
(CH), 36.41 (CH2), 40.10 (CH2), 48.39 (OCH3), 79.35
(C1). Mass spectrum, m/z (Irel, %): 166 (14) [M]+, 135
(6), 110 (9), 109 (100), 94 (8), 79 (8), 41 (7). Found,
%: C 79.71; H 11.25. C11H18O. Calculated, %:
C 79.46; H 10.91. M 166.26.
Ethyl 2-(adamantan-1-yl)-3-oxobutanoate (3).
Yield 76%, bp 146–149°C (1 mm). IR spectrum, ν,
1
cm–1: 2978, 2849 (C–H); 1745, 1703 (C=O). H NMR
spectrum, δ, ppm: 1.25 t (3H, J = 7 Hz), 1.60–1.79 m
(12H, CH2), 1.96 m (3H, CH), 2.21 s (3H), 3.17 s (1H,
CH), 4.12–4.17 m (2H, OCH2). 13C NMR spectrum,
δC, ppm: 14.28 (CH3), 28.64 (CH), 32.21 (CH3), 36.70
(CH2), 37.05 (CH2), 40.13 (C1), 60.82 (CH), 69.95
(CH2), 168.75 (C=O), 203.45 (C=O). Mass spectrum,
m/z (Irel, %): 264 (3) [M]+, 222 (10.5), 193 (0.6), 176
(1.1), 165 (4), 136 (12), 135 (100), 119 (7.5), 106
(1.6), 105 (4.7), 93 (10), 79 (10), 43 (15). Found, %:
C 72.91; H 9.38. C16H24O3. Calculated, %: C 72.69;
H 9.15. M 264.36.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 4-03-97029r_povolzh’e-a) and by the Council for
Grants at the President of the Russian Federation
(program no. SP-4810.2013.4).
REFERENCES
1. Kon’kov, S.A., Cand. Sci. (Chem.) Dissertation, Samara,
2-(Adamantan-1-yl)-1,3-diphenylpropane-1,3-di-
2010.
one (5). Yield 79%, mp 210–211°C. IR spectrum, ν,
2. Turmasova, A.A., Spesivaya, E.S., and Konshina, Dzh.N.,
1
cm–1: 2911, 2849 (C–H); 1707, 1739 (C=O). H NMR
Russ. Chem. Bull., Int. Ed., 2012, vol. 61, p. 1733.
spectrum, δ, ppm: 1.53–1.94 m (12H, CH2), 2.04 m
(3H, CH), 5.41 s (1H, CH), 7.35–7.39 m (4H), 7.47–
7.51 m (2H), 7.88–7.90 m (4H). 13C NMR spectrum,
δC, ppm: 29.13 (CH), 39.86 (CH2), 40.30 (CH2), 45.53
(C1), 63.61 (CH); 128.47, 128.84, 133.19, 138.38 (Ph);
194.20 (C=O). Mass spectrum, m/z (Irel, %): 358 (2.7)
[M]+, 340 (21), 253 (19), 252 (10), 135 (5), 105 (100),
93 (4), 92 (6), 91 (7), 79 (6), 77 (33), 67 (2), 41 (2).
Found, %: C 83.91; H 7.60. C25H26O2. Calculated, %:
C 83.76; H 7.31. M 358.47.
3. Turmasova, A.A., Konshin, V.V., and Konshina, Dzh.N.,
Russ. J. Gen. Chem., 2014, vol. 84, p. 1273.
4. Lloris, M.E., Marquet, J., and Moreno-Manas, M.,
Tetrahedron Lett., 1990, vol. 31, p. 7489.
5. Gonzales, A., Guell, F., Marquet, J., and Moreno-
Manas, M., Tetrahedron Lett., 1985, vol. 26, p. 3735.
6. Stetter, H. and Rauscher, E., Chem. Ber., 1960, vol. 93,
p. 2054.
7. Stepanov, F.N., Sidorova, L.I., and Dovgan’, N.A.,
Zh. Org. Khim., 1972, vol. 8, p. 1834.
Dimethyl 2-(adamantan-1-yl)malonate (7). Yield
90%, bp 129–130°C (1 mm). H NMR spectrum, δ,
8. Pilyavskii, V.S., Khil’chevskii, A.I., and Petrenko, A.E.,
1
Katal. Neftekhim., 2001, nos. 9–10, p. 103.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016