2-(2-hydroxyphenyl)-2-adamantanol in Ritter reaction

Article abstract of DOI:10.1134/S1070428011110054

2-Substituted 4H-1,3-benzoxazines were obtained by the condensation of 2-(2-hydroxyphenyl)-2-adamantanol with aromatic and aliphatic nitriles in trifluoroacetic acid. With acetonitrile the classic product of Ritter reaction, a secondary amide, was isolate

Full text of DOI:10.1134/S1070428011110054

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1686−1689. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.A. Osyanin, E.A. Ivleva, Yu.N. Klimochkin, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 11, pp. 1654−1657.
2-(2-Hydroxyphenyl)-2-adamantanol in Ritter Reaction
V. A. Osyanin, E. A. Ivleva, and Yu. N. Klimochkin
Samara State Technical University, Samara, 443100 Russia
e-mail: orgchem@samgtu.ru
Received March 2, 2011
Abstract—2-Substituted 4H-1,3-benzoxazines were obtained by the condensation of 2-(2-hydroxyphenyl)-2-
adamantanol with aromatic and aliphatic nitriles in trifluoroacetic acid. With acetonitrile the classic product of
Ritter reaction, a secondary amide, was isolated.
DOI: 10.1134/S1070428011110054
In reactions of o-hydroxybenzyl alcohols with nitriles
under the acid catalysis both 2-substituted 4H-1,3-ben-
zoxazines and classic products of Ritter reaction, second-
ary amides, may be obtained [1–3]. The three-component
condensation of 2-naphthol, aromatic aldehydes, and
acetonitrile which presumably proceeds through an in-
termediate formation of 1-hydroxymethyl-2-naphthols is
known to afford in the presence of protic acids or Lewis
acids amides of the naphthalene series [4–6]. Yet the
information on the factors governing the direction of the
reaction is exceedingly poor.
We chose as the initial o-hydroxybenzyl alcohol
a sterically loaded 2-(2-hydroxyphenyl)-2-adamantanol
(I) that at the dehydration in acid medium was capable of
the formation of the relatively stable resonance-stabilized
o-hydroxybenzyl carbocation existing in a protolytic
equilibrium with the corresponding o-methylenequinone
A.As nitriles aromatic nitriles, spatially hindered nitriles
containing an adamantine moiety, ethyl cyanoacetate,
and acetonitrile were used. The reaction was carried out
in trifluoroacetic acid at 0–20°C. At the dissolution of
the colorless phenolalcohol I a red-orange solution was
Scheme 1.
R
C
R
HO
+
OH OH
N
O
+
N
OH
CF3COOH
_H2O
RCN
+
_H
I
IIа_IIg
_
+
H
_
+
H2O
H
O
O
CH3 NH OH
A
III
R = Ph (a), 4-BrC6H4 (b), 4-NO2C6H4 (c), 4-EtO2CC6H4 (d), CH2CO2Et (e), 1-Ad (f), CH2-1-Ad (g).
1686

2-(2-HYDROXYPHENYL)-2-ADAMANTANOL IN RITTER REACTION
1687
Scheme 2.
R
+
+
.
.
+
O
N
O
N
O
.
_CN
.
_R
m/z 226
m/z 252
analyses were carried out on an automatic CHNS-analyzer
EuroVector EA-3000.
obtained. On adding the equimolar quantity of nitrile the
bright color of the solution fast becomes lighter. Note
that the reaction temperature should not exceed 20°C
and the nitrile should be quickly added to the solution
of alcohol I in CF3COOH to avoid the oligomerization
of compound I.
4-(Adamantyl-2′-spiro)-2-phenyl-4H-1,3-
benzoxazine (IIa). To a solution of 0.2 g (0.82 mmol)
of 2-(2-hydroxyphenyl)-2-adamantanol (I) [7] in 3 ml
of trifluoroacetic acid at 0°C was quickly added 0.084 g
(0.82 mmol) of benzonitrile. When the initial red-orange
color of the solution disappeared the solvent was distilled
off in a vacuum, the residue was evaporated with toluene,
then 5 ml of methanol was added, the mixture obtained
was heated to boiling, and afterwards it was kept for 24 h
at –15°C. The separated precipitate was filtered off and
recrystallized from methanol. Yield 0.18 g (67%), color-
less crystals, mp 132–134°C. IR spectrum, ν, cm–1: 3086,
3070, 3036 (C–Harom), 2978, 2959, 2928, 2889, 2846
(C–HAd), 1654 (C=N), 1608 (C=C), 1582, 1481, 1284,
1450, 1203, 1180, 1103, 1053, 1026, 746, 690. 1H NMR
spectrum, δ, ppm: 1.62 d (2HAd, J 11.7 Hz), 1.83 br.s
(4HAd), 2.01 s (2HAd), 2.20–2.35 m (4HAd), 2.84 d (2HAd,
J 12.6 Hz), 7.13–7.35 m (3Harom), 7.45–7.55 m (3Harom),
7.83 d (1Harom, J 8.1 Hz), 8.20 d (2Harom, J 6.7 Hz). Mass
spectrum, m/z (Irel , %): 329 (17) [M]+, 252 (14) [M –
Ph]+, 226 (100) [C16H18O]+, 211 (5), 183 (26), 169 (16),
115 (12), 103 (18). Found, %: C 83.76; H 7.11; N 4.20.
C23H23NO. Calculated, %: C 83.85; H 7.04; N 4.25.
M 329.44.
All nitrlies save acetonitrile afforded in 55–82% yields
2-substituted 4H-1,3-benzoxazines IIa–IIg.
The reaction with acetonitrile was carried out in a large
excess of the latter. The reduced polarity of the reaction
mixture evidently decreased the possibility of the intra-
molecular nucleophilic attack and led to the formation of
the classic Ritter reaction product, secondary amide III.
IR spectra of compounds IIa–IIg contain strong
absorption bands corresponding to the vibrations of
the C–H bonds of the adamantane moiety in the region
2940–2840 cm–1, and also of the C=N bond in the region
1623–1674 cm–1. In the 1H NMR spectra the signals of the
adamantyl protons appear in the region 1.51–4.11 ppm. In
the mass spectra of benzoxazines IIa–IIg the molecular
ion peaks are of low intensity. The main direction of the
fragmentation is the ejection of the substituent in the
position 2 of the benzoxazine ring followed by the loss
of the CN fragment.
In the IR spectrum of amide III a wide absorption band
is observed in the region 3400–2300 cm–1 belonging to
the vibrations of the NH and OH groups involved in the
4-(Adamantyl-2′-spiro)-2-(4-bromophenyl)-4H-
1,3-benzoxazine (IIb) was obtained from alcohol I and
4-bromobenzonitrile. Yield 60%, colorless crystals, mp
160–162°C (methanol–ethyl acetate). IR spectrum, ν,
cm–1: 3070 (C–Harom), 2908, 2851 (C–HAd), 1655 (C=N),
1589, 1485, 1454, 1284, 1203, 1099, 1056, 1011, 760.
1H NMR spectrum, δ, ppm: 1.59 d (2HAd, J 12.5 Hz),
1.68–1.74 m (4HAd), 1.91 s (2HAd), 2.15–2.23 m (4HAd),
2.72 d (2HAd, J 11.7 Hz), 7.20–7.34 m (3Harom), 7.81 d.d
(1Harom, J 7.8, 1.2 Hz), 7.92 d (2H, 2',6'-Harom, J 8.1 Hz),
8.02 d (2H, 3,’5’-Harom, J 8.1 Hz). Mass spectrum, m/z
(Irel , %): 407 (1) [M]+, 252 (6) [M – BrC6H4]+, 226 (100)
[C16H18O]+, 211 (5), 183 (35), 169 (15), 131 (25), 115
1
formation of hydrogen bonds. The H NMR spectrum
contains singlet signals from the protons of NH and OH
groups at 6.25 and 9.87 ppm respectively.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Shimadzu FTIR-8400S from pellets with KBr. 1H NMR
spectra were registered on a spectrometer Bruker AM-
400 (400 MHz), solvent CDCl3, internal reference TMS.
Mass spectra were measured on an instrument Finnigan
Trace DSQ, ionizing electrons energy 70 eV. Elemental
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

OSYANIN et al.
1688
(24), 103 (27), 102 (24). Found, %: C 67.73; H 5.49;
N 4.15. C23H22BrNO. Calculated, %: C 67.65; H 5.43;
N 3.43. M 408.34.
[M]+, 310 (1) [M – C2H5]+, 294 (2) [M – C2H5O]+, 267
(4), 252 (5) [M – CH2CO2C2H5]+, 226 (83) [C16H18O]+,
211 (6), 183 (49), 172 (25), 169 (23), 131 (50), 115 (43),
107 (43), 103 (37), 41 (100) [CH2CNH]+. Found, %:
C 74.40; H 7.37; N 4.08. C21H25NO3. Calculated, %:
C 74.31; H 7.42; N 4.13. M 339.43.
4-(Adamantyl-2′-spiro)-2-(4-nitrophenyl)-4H-
1,3-benzoxazine (IIc) was obtained from alcohol I and
4-nitrobenzonitrile. Yield 58%, light-yellow crystals,
mp 173–175°C (ethyl acetate). IR spectrum, ν, cm–1:
3109, 3078, 3055 (C–Harom), 2908, 2854 (C–HAd), 1659
(C=N), 1601 (C=C), 1528 (NO2), 1481, 1358, 1338
(NO2), 1312, 1285, 1204, 1103, 1065, 860, 759, 706.
1H NMR spectrum, δ, ppm: 1.61 d (2HAd, J 12.7 Hz),
1.80–1.83 m (4HAd), 1.96 C (2HAd), 2.16 C (2HAd), 2.21 d
2-(1-Adamantyl)-4-(adamantyl-2′-spiro)-4H-1,3-
benzoxazine (IIf) was obtained from alcohol I and
adamantane-1-carbonitrile. Yield 82%, colorless crystals,
mp 153–154°C (methanol–ethyl acetate). IR spectrum, ν,
cm–1: 3035 (C–Harom), 2905, 2847 (C–HAd), 1682 (C=N),
1
1485, 1454, 1242, 1207, 1099, 1053, 748. H NMR
(2HAd, J 13.2 Hz), 7.19–7.23 m (2Harom), 7.29 t.d (1Harom
,
spectrum, δ, ppm: 1.49 d (2HAd, J 12.1 Hz), 1.73 br.s
(9HAd), 1.87 s (2HAd), 1.95–2.03 m (12HAd), 2.12 d
(2HAd, J 12.1 Hz), 2.70 d (2HAd, J 11.4 Hz), 6.99 d (1H,
8-Harom, J 8.2 Hz), 7.08 t (1Harom, J 7.4 Hz), 7.18 d.d
(1Harom, J 7.8, 7.4 Hz), 7.70 d (1H, 5-Harom, J 7.8 Hz).
Mass spectrum, m/z (Irel, %): 387 (4) [M]+, 252 (1) [M –
Ad]+, 226 (100) [C16H18O]+, 211 (5), 183 (20), 169 (8),
158 (6), 145 (5), 135 (5) [Ad]+, 131 (7), 107 (7). Found,
%: C 83.75; H 8.64; N 3.56. C27H33NO. Calculated, %:
C 83.68; H 8.58; N 3.61. M 387.56.
2-(1-Adamantylmethyl)-4-(adamantyl-2′-spiro)-
4H-1,3-benzoxazine (IIg) was obtained from alcohol I
and 1-adamantylacetonitrile. Yield 75%, colorless crys-
tals, mp 91–92°C (methanol–ethyl acetate). IR spectrum,
ν, cm–1: 3067, 3036 (C–Harom), 2897, 2849 (C–HAd),
1682 (C=N), 1481, 1450, 1207, 1188, 1188, 1142, 1099,
937, 752. 1H NMR spectrum, δ, ppm: 1.51–1.76 m
(18HAd), 1.90–2.01 m (7HAd), 2.15 d (2HAd, J 11.7 Hz),
2.20 s (2H, CH2), 2.72 d (2HAd, J 12.1 Hz), 6.97 d.d (1H,
8-HapOm, J 7.8, 1.6 Hz), 7.11 t.d (1Harom, J 7.8, 1.6 Hz),
J 6.6, 1.4 Hz), 7.82 d (1Harom, J 6.8 Hz), 8.26–8.33 m
(4Harom). Mass spectrum, m/z (Irel , %): 374 (1) [M]+, 252
(9) [M – NO2C6H4]+, 226 (100) [C16H18O]+, 211 (5), 183
(43), 169 (24), 158 (25), 131 (50), 115 (38), 103 (46), 102
(24). Found, %: C 73.84; H 5.86; N 7.54. C23H22N2O3.
Calculated, %: C 73.78; H 5.92; N 7.48. M 374.44.
Ethyl 4-[4-(adamantyl-2′-spiro)-4H-1,3-
benzoxazin-2-yl]benzoate (IId) was obtained from
alcohol I and ethyl 4-cyanobenzoate. Yield 55%, color-
less crystals, mp 113–114°C (methanol–ethyl acetate).
IR spectrum, ν, cm–1: 3085 (C–Harom), 2974, 2908, 2851
(C–HAd), 1713 (C=O), 1647 (C=N), 1609 (C=C), 1570,
1454, 1273, 1204, 1099, 1057, 756. 1H NMR spectrum, δ,
ppm: 1.31 t (3H, CH3, J 7.2 Hz), 1.53 d (2HAd, J 12.5 Hz),
1.71–1.76 m (4HAd), 1.89 s (2HAd), 2.03 s (2HAd), 2.11 d
(2HAd, J 12.9 Hz), 2.66 d (2HAd, J 11.4 Hz), 4.32 q (2H,
CH2CH3, J 7.2 Hz), 7.23 d.d (1H, 6-Harom, J 7.8, 2.0 Hz),
7.29–7.35 m (2H, 7,8-Harom), 7.81 d.d (1H, 5-Harom, J 7.8,
1.2 Hz), 8.05 d (2H, 2’,6’-Harom, J 8.2 Hz), 8.19 d (2H,
3’,5’-Harom, J 8.2 Hz). Mass spectrum, m/z (Irel , %):
401 (4) [M]+, 252 (14) [M – CO2EtC6H4]+, 226 (100)
[C16H18O]+, 211 (5), 183 (22), 169 (7), 131 (8), 103 (5).
Found, %: C 77.85; H 6.71; N 3.54. C26H27NO3. Calcu-
lated, %: C 77.78; H 6.78; N 3.49. M 401.50.
7.20 t.d (1Harom, J 7.8, 1.6 Hz), 7.75 d.d (1H, 5-Harom
,
J 7.8, 1.6 Hz). Mass spectrum, m/z (Irel , %): 401 (<1)
[M]+, 266 (1) [M – Ad]+, 252 (<1) [M – CH2Ad]+, 226
(100) [C16H18O]+, 225 (26), 211 (5), 183 (29), 169 (15),
158 (13), 135 (62) [Ad]+, 131 (22), 107 (33). Found,
%: C 83.70; H 8.83; N 3.45. C28H35NO. Calculated, %:
C 83.74; H 8.78; N 3.49. M 401.59.
N-[2-(2-Hydroxyphenyl)adamant-2-yl]ethanamide
(III). To a solution of 0.2 g (0.82 mmol) of alcohol I in
1 ml of trifluoroacetic acid at 20°C was quickly added
0.34 g (8.2 mmol) of acetonitrile. When the initial red-
orange color of the solution disappeared the solvent was
distilled off in a vacuum, the residue was evaporated with
toluene, then 3 ml of methanol was added, the mixture
obtained was heated to boiling, and afterwards it was
kept for 24 h at –70°C. The separated precipitate was
filtered off and recrystallized from aqueous methanol.
Ethyl 2-[4-(adamantyl-2′-spiro)-4H-1,3-
benzoxazin-2-yl]acetate (IIe) was obtained from
alcohol I and ethyl cyanoacetate. Yield 62%, colorless
crystals, mp 125–127°C (methanol–ethyl acetate). IR
spectrum, ν, cm–1: 2982, 2920, 2897 (C–HAd), 1655, 1620
(C=O/C=N), 1593 (C=C), 1443, 1285, 1204, 1142, 1057,
1
779, 756. H NMR spectrum, δ, ppm: 1.19 t (3H, CH3,
J 7.0 Hz), 1.47–1.75 m (8H, CH2, 6HAd), 1.87 br.s (2H,
CH2), 2.08–2.11 m (4HAd), 2.60 br.s (2HAd), 4.11 q (2H,
CH2CH3, J 7.0 Hz) 6.98 d (1H, 8-Harom, J 7.8 Hz), 7.08 t
(1Harom, J 7.0 Hz), 7.19 t (1Harom, J 7.0 Hz), 7.69 d (1H,
5-Harom, J 7.8 Hz). Mass spectrum, m/z (Irel, %): 339 (2)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

2-(2-HYDROXYPHENYL)-2-ADAMANTANOL IN RITTER REACTION
1689
Yield 0.12 g (51%), colorless crystals, mp 70–72°C. IR
spectrum, ν, cm–1: 3500–2800 (NH, OH), 2904, 2854
(C–HAd), 1624 (C=O), 1597 (C=C), 1562, 1450, 1354,
of the Council on grants at the President of the Russian
Federation (State Program for support of young Russian
scientists, grant MK-3368.2011.3) using the equipment
of the Center of Collective Exploitation “Study of physi-
cochemical properties of substances and materials.”
1
1227, 1211, 1107, 1033, 752. H NMR spectrum, δ,
ppm: 1.55 d (1HAd, J 13.3 Hz), 1.65–1.74 m (6HAd),
1.83–1.90 m (5H, CH3, 2HAd), 1.97 d (2HAd, J 13.3 Hz),
2.17 d (1HAd, J 12.8 Hz), 2.64 s (1HAd), 3.87 s (1HAd),
6.25 s (1H, NH), 6.83 t (1H, 5-Harom, J 8.2 Hz), 6.87 d (1H,
3-Harom, J 8.2 Hz), 7.11 t (1H, 4-Harom, J 8.2 Hz), 7.25 d
(1H, 6-Harom, J 8.2 Hz), 9.87 br.s (1H, OH). Mass spec-
trum, m/z (Irel , %): 285 (30) [M]+, 242 (6) [M – CH3CO]+,
226 (100) [C16H18O]+, 211 (17), 183 (50), 169 (26), 158
(20), 145 (20), 131 (19), 115 (11), 107 (15). Found, %:
C 75.70; H 8.07; N 4.95. C18H23NO2. Calculated, %:
C 75.76; H 8.12; N 4.91. M 285.38.
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ACKNOWLEDGMENTS
6. Das, B., Laxminarayana, K., Thirupathi, P., and Ra-
marao, B., Synlett., 2007, p. 3103.
The study was carried out under the financial support
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011