Synthesis and reactivity of aldehydes of the adamantane series

Article abstract of DOI:10.1023/A:1013178326353

1-Adamantanecarbonitriles are very active in the Stephen reaction, which allows synthesis of the corresponding aldehydes in high yields. Electron-acceptor substituents in the 3 position of the adamantine nucleus exert almost no effect on the yield of aldehydes. Separation of the nitrile group and the adamantane nucleus by one methylene group results in a complete loss of reactivity. A quantitative study of the reactivity of the synthesized aldehydes in the oximation reaction was performed.

Full text of DOI:10.1023/A:1013178326353

Russian Journal of General Chemistry, Vol. 71, No. 7, 2001, pp. 1121 1125. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 7, 2001,
pp. 1187 1192.
Original Russian Text Copyright
2001 by Voloboev, Butenko, Novakov.
Synthesis and Reactivity of Aldehydes of the Adamantane Series
S. N. Voloboev, L. N. Butenko, and I. A. Novakov
Volgograd State Technical University, Volgograd, Russia
Received January 10, 2000
Abstract 1-Adamantanecarbonitriles are very active in the Stephen reaction, which allows synthesis of the
corresponding aldehydes in high yields. Electron-acceptor substituents in the 3 position of the adamantine
nucleus exert almost no effect on the yield of aldehydes. Separation of the nitrile group and the adamantane
nucleus by one methylene group results in a complete loss of reactivity. A quantitative study of the reactivity
of the synthesized aldehydes in the oximation reaction was performed.
Stephen and Sonn Moller reductions of aromatic
and certain aliphatic nitriles and imidoyl chlorides
with tin(II) chloride, followed by hydrolysis of the
reduction products, gives rise to the corresponding
aldehydes [1]. Reduction and hydrolysis of nitriles
and imidoyl chlorides, containing an adamantlyl
fragment, may prove a convenient synthetic route to
hardly available adamantanecarbaldehydes.
oxy-1-adamantanecarbonitrile (I IV), 1,3-adamantane-
dicarbonitrile (V), 1-adamantylacetonitrile (VI), and
N-phenyl1-adamantanecarboximidoyl chloride (VII)
[2].
It is khown that the Stephen reduction of aliphatic
nitriles most frequently provides low yields of the
corresproding aldehydes because of the side formation
of iminoesters [3] and N,N -diacyl-1,1-diaminoalkanes
[4]. We found that the Stephen reduction of nitrile V
occurs fast and gives 1-adamantanecarbaldehyde
(VIII) in high yield.
For the objects for study we used 1-adamantane-
carbonitrile (I), 3-bromo-1-adamantanecarbonitrile
(II), 3-chloro-1-adamantanecarbonitrile (III), 3-hydr-
H2O
CN SnCl , HCl
[
CH=NH]2 H2SnCl6
CN
2
I
VIII
Similar results were obtained with nitriles II
and III.
It should be noted that the reduction of nitrile II
involves no substitution of bromine by chlorine. This
was shown by mass spectral studies of the reaction
products.
Hlg
CN
It can be supposed that the high reactivity of
1-adamantanecarbonitriles derives from the consi-
derable electron-donor effect of the adamantyl group,
which is obviously not wiped out by the electron-
acceptor effect of the 3-substituents in the adamantane
nucleus.
II, III
SnCl2, HCl
[
CH=NH]2 H2SnCl6
Hlg
The reduction of nitrile IV involves two concurrent
reactions.
H2O
Hlg
CHO
The fraction of aldehyde X in the reaction products
depends on reaction conditions and varies from 5
to 18%. Increased reaction temperature and SnCl2 :ni-
trile IV molar ratio increase the fraction of aldehyde
X.
IX, X
Hlg = Br (II, IX), Cl (III, X).
1070-3632/01/7107-1121$25.00 2001 MAIK Nauka/Interperiodica

1122
VOLOBOEV et al.
nucleus [8] favors partial transfer of the deficit of elec-
tron density from the aldimine carbon on the 3-CN
group, making the latter less reactive.
HO
CN
The above reasoning led us to expect that the
Stephen reaction of aldehyde XII followed by hydro-
lysis of the reduction products would allow synthesis
of dialdehyde XIII. We succeded in effecting this re-
action sequence to obtain dialdedyde XIII in 60 66%
IV
HO
CHO
CHO
(1) SnCl2, HCl
(2) H2O
XI
yield.
(1) SnCl2, HCl;
(2) H2O
Cl
OHC
CHO
NC
CN
X
XII
XIII
It is known that aliphatic dicarbonitriles fail to
undergo Stephen reduction, and the reaction gives
nitrilium salts [5] or cyclization products [6, 7]. In
this connection we considered it of interest to bring
into the Stephen reaction dinitrile V which, having a
rigid carcass, does not tend to cyclization.
The fraction of dialdehyde XIII in the reduction
products is 92 94%; the moderate isolable yield of
dialdehyde XIII can be explained by its partial solu-
tion in water.
Aldehyde VIII readily trimerizes [9], which makes
it difficult to operate. The synthesized 3-substituted
adamantanecarbaldehydes are not prone to spontane-
ous polymerization, most probably, on account of
disturbed symmetry of the molecule and increased
vibrational and rotational mobility of its units. Evi-
dence for this assumption was obtained from analysis
of the Stewart Briegleb models.
At the SnCl2 :dinitrile V molar ratio of 2:1, only
one nitrile group could be selectively reduced. Subse-
quent hydrolysis of the reduction products gave 3-cya-
no-1-adamantanecarbaldehyde (XII) in 83 87% yield.
(1) SnCl2, HCl;
2
NC
CN (2) H O
NC
CHO
To obtain 1-adamantylethanal XIV, we tried to
effect the Stephen reaction hydrolysis sequence with
nitrile VI. However, aldehyde XIV was not found
even if the reaction mixture was allowed to stand for
4 days. This result can be explained both by different
inductive effects of the 1-AdCH2 and 1-Ad groups on
V
XII
The fraction of 1,3-adamantanedicarbaldehyde
(XIII) in the reaction products normally does not
exceed 3%. To direct the reaction to dialdehyde XIII
formation, we used an excess of tin(II) chloride (up
to 5 mol of SnCl2 per 1 mol of dinitrile V). However,
the fraction of dialdehyde XIII could not be increased
in this way.
*
*
the reaction center (
0.26,
0.10) [10]
1-AdCH2
and by different steric1e-Affdects of these groups. Accord-
ing to [10], the 1-AdCH2 group exerts a stronger
steric effect than 1-Ad. The steric constants (Es) of the
1-AdCH2 and 1-Ad groups are 2.00 and 1.51,
respectively.
The observed reaction direction can be explained
by the strong deficit of electron density on the ald-
imine carbon atom, which is produced by the positive
charge generated by protonation of the adjacent nitro-
gen atom in the course of reduction of the first nitrile
group.
The yields, constants, spectra, and elemental ana-
lyses of aldehydes VIII XIII are listed in Table 1.
Compound VII under conditions of the Sonn
Moller reaction converts into N-phenyl-(1-adaman-
tyl)chloromethaniminium tetrachlorostannite (XV).
2[H2SnCl4 NC
CN H2SnCl4]
C=N C6H5
Cl
+
CH=NH2]2 SnCl62
2HCl
[NC
VII
+
SnCl2, HCl
+ SnCl4 + 2H2SnCl4
[
C=NH C6H5] HSnCl4
Cl
The cage effect resulting from the overlap of or-
bital backsides of bridgehead atoms of the adamantane
XV
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 7 2001

SYNTHESIS AND REACTIVITY OF ALDEHYDES OF THE ADAMANTANE SERIES
1123
Treatment of complex XV with water yields N-
phenyl-1-adamantanecarboxamide.
was inconsiderable, and we did not take it into
account in calculating the rate constants.
To assess the effect of the 3-substituents in the
adamantane nucleus on the reactivity of the carbonyl
group of the synthesized adamantanecarbaldehydes,
we performed a quantitative study of the reactivity of
the latter in the oximation reaction. The objects for
study were aldehydes VIII XII.
It follows from data in Table 2 that substituents in
the 3 position of the adamantane nucleus appreciably
affect the reactivity of the carbonyl group. The reac-
tivity increases with the inductive constant * [12].
Treatment of the resulting data in terms of the Taft
equation [13] with exception of compound I showed
that the logarithms of the rate constants correlate well
with the inductive constants of the substituents; the
correlation coefficient is 0.992.
The rate constants of oxime formation were esti-
mated based on the concentrations of unreacted hydr-
oxylamine, which were measured by iodometric titra-
tion [11]. It was found that the oximation reaction is
an irreversible second-order reaction. The reaction
order in each reagent is one. Table 2 lists the mean
rate constants of oximation of aldehydes VIII XII.
The conversions are all higher than 70%. The decom-
position of the oximes during kinetic measurements
The high correlation coefficient is likely to suggest
that the 3-substituents exert an only slight steric effect
on the reactivity of the carbonyl group and that the
rate constants are controlled exclusively by the in-
ductive constants of the substituents.
Table 1. Yields, melting points, IR, 1H NMR, and mass spectra, and elemental analyses of aldehydes VIII XIII
mp, C,
Comp. Yield,
no.
(solvent
for crystal-
lization)
IR spectrum,
1H NMR spectrum,
, ppm
Mass spectrum, m/z
(Irel, %)
1
%
, cm
VIII 95
125 128
(hexane)
2686 (C H in
1.66 m (H4,6,10), 1.73 m 164 (11.3), 136 (18.1), 135 (100), 106 (13.4),
CHO),1700(C=O), (H3,5,7), 2.05 m (H2,8,9), 93 (25.2), 91 (14.5), 81 (8.3), 79 (21.0),
1340, 1100, 990 8.86 s (CHO)
(Ad)
77 (11.7), 67 (14.0), 65 (4.2), 55 (8.3), 53
(4.8), 44 (7.6), 41 (14.4), 29 (18.8)
IX
X
91
88
104 106
(hexane)
2666 (C H in
1.60 d (H8,9), 2.04 m 242/244 (14.4/14.1), 214/216 (10.7/0.5), 163
CHO),1700(C=O), (H4,6,10), 2.08 m (H5,7), (80.1), 135 (100), 107 (8.9), 93 (26.0), 92
1340, 1104, 968 2.13
s
(H2), 9.16
s
(7.6), 91 (9.4), 81 (18.3), 79 (25.6), 67 (20.5),
65 (13.1), 56 (8.8), 55 (4.9), 53 (2.6), 44 (2.9),
42 (9.6), 41 (11.0), 29 (19.6)
(Ad), 692 (C Br) (CHO)
114 116
(hexane)
2666 (C H in
1.63 d (H8,9), 2.02 m 198/200 (16.3/5.3), 170/172 (5.1/1.6), 163
CHO),1700(C=O), (H4,6,10), 2.10 m (H5,7), (79.6), 135 (100), 107 (10.4), 93 (28.8), 92
1340, 1100, 968 2.17 s (H2), 9.16 s (CHO) (4.9), 91 (8.3), 81 (20.4), 79 (19.0), 67 (32.3),
(Ad), 788 (C Cl)
2668 (C H in
65 (15.4), 56 (7.1), 55 (5.5), 53 (4.7), 44 (1.8),
42 (30.9), 41 (24.6), 35 (11.4), 37 (3.7), 9
(17.8)
XI
66
87
200 202
(toluene
1.57 d (H8,9), 1.68 m 180 (10.2), 152 (100), 151 (31.0), 96 (8.7), 95
CHO),1700(C=O), (H4,6,10), 2.01 m (H5,7), (4.1), 94 (63.2), 42 (39.5), 41 (19.4), 29
hexane, 1: 1) 3420 (O H), 1340, 2.09 s (H2), 3.65 s (OH), (13.6)
1100, 968 (Ad)
2660 (C H in
9.02 s (CHO)
XII
169 171
1.67 d (H8,9), 1.98 m 189 (10.7), 163 (83.1), 161 (20.3), 147 (13.3),
(benzene) CHO), 2232 (CN), (H4,6,10), 2.12 m (H5,7), 135 (100), 107 (17.8), 93 (74.1), 81 (21.4), 79
1720 (C=O), 1348, 2.24 s (H2), 9.24 s (CHO) (20.6), 67 (32.6), 65 (13.8), 56 (11.9), 53
1100, 976 (Ad)
2682 (C H in
(9.4), 44 (3.2), 42 (19.6), 41 (18.3), 40 (18.3),
29 (17.4)
a
XIII 65
1.66 m (H4,6,8,9,10), 2.11 192 (11.1), 163 (73.5), 135 (100), 107 (19.4),
CHO),1700(C=O), m (H5,7), 2.19 s (H2), 9.09 93 (64.8), 81 (19.6), 79 (19.8), 67 (41.0), 65
1340, 1104, 968 s (CHO)
(Ad)
(11.7), 56 (13.4), 53 (8.3), 44 (3.1), 42 (15.5),
41 (18.6), 40 (18.0), 29 (16.4)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 7 2001

1124
VOLOBOEV et al.
Table 1. (Contd.)
Found, %
Calculated, %
H
Compound no.
Formula
C
H
Hlg
C
Hlg
VIII
IX
X
XI
XII
XIII
79.88
54.09
66.19
73.41
75.19
74.42
10.0
6.6
8.10
9.08
8.10
8.51
C11H16O
C11H15BrO
C11H15ClO
C11H16O2
C12H15NO
C12H16O2
80.48
54.53
66.49
73.33
76.19
75.00
9.75
6.17
7.55
8.88
7.93
8.33
32.60
17.64
32.92
17.88
a
20
20
bp 143 C (1 mm), d 1.0960, n 1.5132.
4
D
Table 2. Oximation of aldehydes I V
k, l mol 1 s
1
S ,
H ,
kJ/mol
G ,
kJ/mol
Product no.
1
J mol 1 K
0 C
10 C
20 C
VIII
IX
X
XI
XII
0.7317
0.7702
0.7832
0.7406
0.8119
1.0848
1.1441
1.1619
1.1201
1.1789
1.6240
1.7246
1.7520
1.6540
1.8107
0.2961
0.2957
0.2957
0.2954
0.2954
24.19
24.48
24.45
24.37
24.57
24.27
24.57
24.54
24.45
24.47
As seen from data in Table 2, the activation para-
meters of the reaction are almost independent of the
structure of the aldehyde. Thus, the substituents in the
3 position of the adamantane nucleus all only slightly
increase the activation parameters. The activation
entropies for the aldehydes in study are small negative
values, which is accounted for by the high reactivity
of the carbonyl group.
of 40 ml of absolute diethyl ether and 23.5 g of tin(II)
chloride was saturated with stirring at 0 5 C with
hydrogen chloride until a real solution, after which
10 g of nitrile I was added in portions so that the
temperature of the reaction mixture did not rise above
5 C. The mixture was stirred at 0 5 C for 2 h and
then left to stand without stirring for 20 h at 20 25 C.
Within this time, 1-adamantylmethanimine hexachloro-
stannate precipitated. The reaction mixture was added
to 200 ml of water and slowly heated to evaporate
the diethyl ether. Heating was discontinued, when the
temperature reached 60 C. At this moment, 1-ada-
mantylmethanimine had completely hydrolyzed to
aldehyde VIII. The suspension of the aldehyde in
water was cooled 20 25 C, the precipitate was filtered
off, washed with water (2 20 ml), dried, and recrys-
tallized. Aldehydes IX XIII were obtained in a
similar way.
EXPERIMENTAL
The IR spectra were obtained on a Specord M-82
1
instrument in Vaseline oil. The H NMR spectra were
measured on
a
Tesla BS-567A spectrometer
(100 MHz), internal reference HMDS, solvent carbon
tetrachloride. The mass spectra were obtained on a
Varian MAT-111 instrument with direct inlet, ioniz-
ing voltage 70 V, emission current 240 A. Chroma-
tographic analysis of the reaction mixtures was per-
formed on a Perkin Elmer LC-1022 Plus chromato-
graph with diode array at 25 C, steel column (250
4 mm), sorbent Ultrasphere ODS (5 m), eluent aceto-
nitrile water, 85:15, flow rate 1 ml/min.
N-Phenyl-(1-adamantyl)chloromethaniminium
tetrachlorostannite (XV). A mixture of 30 ml of
absolute diethyl ether and 13.8 of tin(II) chloride was
saturated with stirring at 0 5 C with hydrogen chlo-
ride until a real solution, after which a solution of
10 g of carboximidoyl chloride VII in 20 ml of ab-
solute diethyl ether was added dropwise. During the
addition, crystals formed and were filtered off, washed
All experiments were peformed in moisture-proof
conditions.
1-Adamantanecarbaldehyde (VIII). A mixture
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 7 2001

SYNTHESIS AND REACTIVITY OF ALDEHYDES OF THE ADAMANTANE SERIES
1125
with absolute diethyl ether and saturated hydrogen
chloride, and dried in a vacuum dessicator over CaCl2
to obtain 19.3 g (98%) of compound XV as a color-
less hygroscopic powder. The product slowly decom-
posed on handling with hydrogen chloride evolution.
Found, %: Cl 34.4; Sn 20.7. C17H22Cl5NSn. Calcu-
lated, %: Cl 33.1; Sn 22.1.
2. No, B.I., Shishkin, E.V., Penskaya, T.V., and Shish-
kin, V.E., Zh. Org. Khim., 1996, vol. 32, no. 7,
p. 1110.
3. Shemyakin, M.M., Maimind, V.I., Tokarev, B.V., and
Karpov, V.I., Zh. Obshch. Khim., 1958, vol. 28, no. 4,
pp. 978 983.
4. Zil’berman, E.N. and Pyryalova, P.S., Zh. Obshch.
Khim., 1963, vol. 33, no. 10, pp. 3420 3425.
5. Zil’berman, E.N., Pyryalova, P.S., and Pomerantse-
va, E.G., Zh. Obshch. Khim., 1964, vol. 34, no. 8,
pp. 2708 2712.
Kinetic measurements. Aldehydes VIII XII in a
buffer solution [0.04 M CH3COONa and 0.04 M
CH3COOH in 75% (v/v) ethanol, pH 6.5] were placed
in a temperature-controlled volumetric flask. Another
volumetric flask was charged with a solution of
hydroxylamine hydrochloride in the same buffer.
After the required temperature had been attained, the
aldehyde solution was added to the hydroxylamine
hydrochloride solution, and the reaction onset time
was marked. Samples (10 ml) were taken in a flask
containing an excess of a 0.04 M solution of iodine
in aqueous potassium iodide, cooled to 0 5 C, after
which an excess of a standard 0.04 M solution of
sodium thiosulfate was added. The excess sodium
thiosulfate was titrated with a standard solution of
iodine in aqueous potassium iodide in the presence of
starch.
6. Zil’berman, E.N. and Pyryalova, P.S., Zh. Org. Khim.,
1965, vol. 1, no. 6, pp. 983 987.
7. Duquette, L.G. and Jonson, F., Tetrahedron, 1967,
vol. 23, no. 12, pp. 4517 4537.
8. Fort, R.S. and Schleyer, P.R., Chem. Rev., 1964,
vol. 64, no. 3, pp. 277 280.
9. Stepanov, F.N. and Dovgan’, N.L., Zh. Org. Khim.,
1968, vol. 4, no. 2, pp. 277 300.
10. Ivanova, L.P., Polis, Ya.Yu., Grava, I.Ya., Ra-
guel’, B.P., Cherkasova, V.A., Khamad, Kh.Dzh., and
Kolobova, T.A., Zh. Org. Khim., 1981, vol. 17, no. 2,
pp. 325 329.
11. Komarov, V.A. and Ivanova, L.P., Zh. Org. Khim.,
1968, vol. 4, no. 5, pp. 760 763.
REFERENCES
12. Cherkasov, A.R., Galkin, V.I., and Cherkasov, R.A.,
Usp. Khim., 1996, vol. 65, no. 8, pp. 695 800.
1. Bartoszewicz, R., Miecznikowska-Stolarczyk, W., and
Oprzsadek, B., Metody redukcji zwisazkow organi-
cznych (Methods of Reduction of Organic Compounds),
Warsaw: Panstw. Wyd. Naukowe, 1956.
13. Pal’m, V.A., Osnovy kolichestvennoi teorii organi-
cheskikh reaktsii (Fundamentals of Quantitative Theory
of Organic Reactions), Leningrad: Khimiya, 1971.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 7 2001