Reaction of nitroso chlorides of the adamantane series with nucleophiles

Article abstract of DOI:10.1007/s11172-015-1177-y

Reactions of nitroso chlorides of 2-alkylydene adamantanes with O- and N-nucleophiles resulted in α-substituted oximes of the adamantane series. Reaction involved 1,4-nucleophilic addition of the nucleophiles to the generated in situ nitroso alkenes actin

Full text of DOI:10.1007/s11172-015-1177-y

2454
Russian Chemical Bulletin, International Edition, Vol. 64, No. 10, pp. 2454—2458, October, 2015
Reaction of nitroso chlorides of the adamantane series with nucleophiles
P. E. Krasnikov, V. A. Osyanin, D. V. Osipov, and Yu. N. Klimochkin
Samara State Technical University,
2
44 ul. Molodogvardeiskaya, 443100 Samara, Russian Federation.
Eꢀmail: VOsyanin@mail.ru
Reactions of nitroso chlorides of 2ꢀalkylydene adamantanes with Oꢀ and Nꢀnucleophiles
resulted in αꢀsubstituted oximes of the adamantane series. Reaction involved 1,4ꢀnucleophilic
addition of the nucleophiles to the generated in situ nitroso alkenes acting as the Michael
acceptors. Reduction of the precursors of nitroso alkenes with sodium cyanoborohydride gave
2
ꢀsubstituted adamantylated oximes.
Key words: adamantane, nitroso chlorides, nitroso alkenes, the Michael reaction.
Vinyl nitroso compounds are known for a long time;
oxy)adamantaneꢀ2ꢀcarbaldehyde (2e) contains triplet at
δ 2.34 of the C≡CH group proton and doublet at δ 3.92 of
however being highly reactive and unstable they are of
little significance for the synthesis compared to other
Michael acceptors and heterodienes.1 They are mainly
applied in the synthesis of 5,6ꢀdihydroꢀ1,2ꢀoxazines via
the CH O group protons with long range spinꢀspin couꢀ
2
—7
4
pling constants J = 2.3 Hz.
Refluxing precursors of nitroso alkenes 2a,d with sodium
azide in methanol in the presence of 15ꢀcrownꢀ5 afforded
selectively αꢀazido oximes 3 in the yields above 90%. Apparꢀ
ent competitive 1,4ꢀaddition of methanol was not detected.
In IR spectra of compounds 3a,b, the azido group vibrations
8
,9
intraꢀ or intermolecular [4+2] cycloaddition to olefins.
Conjugated nitroso alkenes can be easily generated in situ
from αꢀhalooximes by treatment with bases.1 Note that
conjugated nitroso alkenes could be isolated pure only in
few cases: in the presence of bulky substituents, halogen
0
–1
appear as the intense bands at 2087 and 2091 cm .
3
,11—14
atoms, and aryl groups at the double bond.
ly, they can be detected only in solutions; their presence is
often evidenced by the blue color of the solution (λ
Typicalꢀ
Reactions of dimeric nitroso chlorides 1a—c with liqꢀ
uid amines (morpholine, piperidine, and benzylamine) and
1,1ꢀdimethylhydrazine were performed in the correspondꢀ
ing amine or hydrazine as a solvent. In some cases, the
addition of amines to nitroso chlorides 1a—c at room temꢀ
perature causes blueꢀgreen color of the reaction solution
due to the presence of unsaturated nitroso compound; the
color gradually fades during the reaction. This fact exꢀ
cludes the possibility of the reaction to occur via the SN1
mechanism and formation of 2ꢀadamantyl carbocation.
Amino oximes 4a—i are unstable in acidic medium
and at heating (they melt with decomposition). For inꢀ
stance, acidꢀmediated decomposition of compound 4a
gives adamantanone (Scheme 2).
≈
max
4
≈
700 nm).
In continuation of our research on chemical properties
of sterically hindered nitroso alkenes,1
work we describe reactions of dimeric nitroso chlorides of
ꢀalkylydeneadamantanes 1a—c and chloro oxime 1d with
5—18
in the present
2
Oꢀ and Nꢀnucleophiles and reduction of nitroso alkenes
generated from compounds 1a—d.
Conjugated nitroso alkenes A are available by treatment
of dimeric nitroso chlorides of 2ꢀalkylydeneadamantanes
a—c or (E)ꢀ1ꢀ(2ꢀchloroadamantꢀ2ꢀyl)ꢀNꢀhydroxyꢀ1ꢀpheꢀ
nylmethaneimine (1d). Compounds 1a—d are capable of
1
nucleophilic conjugate addition to give the corresponding
Instability of such oximes can be explained in terms of
a Beckmann rearrangement of the second type (Werner
rearrangement), which can be regarded as a particular case
2,2ꢀdisubstituted adamantane derivatives (Scheme 1).
Nitroso alkenes generated by treating the staring comꢀ
1
9,20
pounds with base (Na CO ) in alcoholic medium (methaꢀ
of the Grob fragmentation.
2
3
nol or propargyl alcohol) produce alkoxy oximes 2a—e in
the yields of 76—93%. IR spectra of compounds 2a—e
αꢀChloro oxime 1d reacts with aqueous ammonia in
dichloromethane to give αꢀamino oxime in 95% yield.
Compound 4i also melts with decomposition producing
adamantanone, benzonitrile, and ammonia.
–
1
exhibit wide absorption bands at 3400—3200 cm charꢀ
acteristic of the hydroxy group vibrations of the oxime
moiety. Mass spectra of methoxy oximes 2a—e reveal the
fragment ion peaks resulted from the loss of the hydroxy
Reduction of dimers 1a,c and chloro oxime 1d with sodiꢀ
um cyanoborohydride in DMF leads to oximes 5a—c. Comꢀ
pounds 5 can resulted from the nucleophilic addition of an
anion complex hydride to the conjugated system of nitroso
1
and methoxy ions. H NMR spectra of oximes 2a—e show
a singlet signals at δ 3.05—3.13 attributed to the methoxy
1
1
group protons. H NMR spectrum of 2ꢀ(propynꢀ2ꢀylꢀ1ꢀ
alkene acting as the Michael acceptor. H NMR spectra of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2454—2458, October, 2015.
066ꢀ5285/15/6410ꢀ2454 © 2015 Springer Science+Business Media, Inc.
1

Nitroso chlorides of adamantane series
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 10, October, 2015
2455
Scheme 1
i. Na CO or an excess of nucleophile.
2
3
Compound
R
H
Me
Et
Ph
H
Me
Et
Ph
H
R´O
—
—
—
—
MeO
MeO
MeO
MeO
Compound
R
H
Me
H
Me
Et
H
H
H
Ph
H
Et
Ph
NR´R″
N(CH )
1a
1b
1c
1d
2a
2b
2c
2d
2e
3a
3b
4a
4b
4c
4d
4e
4f
4g
4h
4i
2
5
N(CH2)5
N(CH CH ) O
2
2 2
N(CH CH ) O
2 2 2
N(CH CH ) O
2 2 2
NHCH Ph
2
NHNMe2
NHNHCONH2
HC≡C—CH O
NH2
—
—
2
H
Ph
—
—
5a
5b
5
c
—
Scheme 2
tane framework. In the 13C NMR spectra (CDCl ), the C(2)
atoms resonate in the range of δ 44.8—49.8.
compounds 5a—c contain the broadened singlets at the range
of δ 2.48—2.84 ascribed to the C(2)H proton of the adamanꢀ
3

2
456
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 10, October, 2015
Krasnikov et al.
13C NMR spectra of the adamantane frameworks of
HAd, J = 12.1 Hz); 2.23 (br.s, 2 H, HAd); 3.05 (s, 3 H, CH3O);
13
8
3
.85 (s, 1 H, OH). C NMR (CDCl ), δ: 8.6 (CH ); 27.1, 27.5,
compounds 2—5 comprise seven signals. Note that the
C(2) atom of 2,2ꢀdisubstituted adamantane skeleton is
strongly deshielded and resonates at δ 60.3—82.1; while,
the oxime carbons are even more deshielded and appear at
3 3
1.7, 32.5, 34.4, 37.7, 48.7 (CH O); 81.5 (CAd(2)); 157.6 (C=N).
3
Found (%): C, 69.82; H, 9.30; N, 6.11. C H NO . Calculated
13
21
2
(
%): C, 69.92; H, 9.48; N, 6.27.
ꢀ(2ꢀMethoxyadamantꢀ2ꢀyl)propanꢀ1ꢀone (E)ꢀoxime (2c).
1
1
δ 151.4—163.9. H NMR spectra contain singlets of the
–1
Yield 86%, m.p. 121—123 °C. IR, ν/cm : 3400—3200 (OH),
2
hydroxy group protons at the range of δ 7.76—8.81. The
1
908, 2851 (CHAd), 1447, 1084, 964, 937, 887, 841, 721. H NMR
protons of the CH=N moieties of 2,2ꢀdisubstituted adaꢀ
mantaneꢀ2ꢀcarbaldehydes resonate in the H NMR specꢀ
(CDCl ), δ: 1.12 (t, 3 H, CH CH , J = 7.6 Hz); 1.54 (d, 2 H,
HAd, J = 11.7 Hz); 1.66—1.72 (m, 4 H, HAd); 1.81—1.88 (m, 4 H,
HAd); 2.13 (d, 2 H, HAd, J = 12.1 Hz); 2.24 (br.s, 2 H, HAd); 2.31
3
2
3
1
tra at δ 6.95—8.06.
Earlier,15 existence of oximes in the most energetically
(q, 2 H, CH CH , J = 7.6 Hz); 3.05 (s, 3 H, CH O); 8.76 (s, 1 H,
2
3
3
13
OH). C NMR (CDCl ), δ: 10.8 (CH CH ); 17.5 (CH CH );
favorable Eꢀconfiguration was suggested. Effects of both
the bulky adamantane skeleton and the substituent at the
bridgehead positions will favor the Eꢀisomer formation.
The NMR and IR spectroscopy data obtained in the
present work for 2,2ꢀdisubsituted adamantanes clearly inꢀ
dicate formation of only one geometrical isomer of oximes,
which in all cases was attributed to Eꢀisomer.
3
3
2
3
2
2
1
–
7.0, 27.7, 31.7, 32.6, 34.6, 37.8, 48.7 (CH O); 82.0 (CAd(2));
3
+
61.2 (C=N). MS, m/z (I (%)): 220 [M – OH] (8), 205 [M –
rel
+
+
CH OH] (51), 188 (8), 165 (100) [C11H17O] , 150
3
+
+
[
C H O] (7), 149 (9), 133 (6), 105 (6), 91 (16) [C H ] .
10 14 7 7
Found (%): C, 70.73; H, 9.65; N, 5.60. C H NO . Calculated
14
23
2
(%): C, 70.85; H, 9.77; N, 5.90.
(2ꢀMethoxyadamantꢀ2ꢀyl)(phenyl)methanone (E)ꢀoxime (2d).
Yield 93%, m.p. 184—186 °C. IR, ν/cm– : 3400—3300 (OH), 2910,
1
2
854 (CHAd), 1493, 1447, 1400, 1358, 1231, 1196, 1099, 1076, 972,
Experimental
1
941, 883, 833, 764, 741, 721, 702. H NMR (CDCl ), δ: 1.48 (d, 2 H,
3
HAd, J = 12.2 Hz); 1.62—1.65 (m, 4 H, HAd); 1.80—1.93 (m, 4 H,
IR spectra were recorded with a Shimadzu IRAffinityꢀ1 specꢀ
trophotometer in the KBr pellets. Mass spectrometry was perꢀ
formed on a Thermo Finnigan Trace DSQ instrument using
direct inlet injection into the ion source; ionizing electron enerꢀ
HAd); 2.08—2.11 (m, 4 H, HAd); 3.30 (s, 3 H, CH O); 7.35—7.45
3
13
(m, 5 H, Ph); 8.25 (s, 1 H, OH). C NMR (CDCl ), δ: 27.0 (CH);
3
27.5 (CH); 31.7 (CH); 32.4 (CH ); 34.3 (CH ); 37.6 (CH ); 48.4
2
2
2
(CH O); 82.1 (C (2)); 128.0 and 128.5 (5 CHPh); 131.4 (CPh);
3
Ad
1
13
+
+
gy was 70 eV. H and C NMR spectra (working frequencies of
00 and 100 MHz, respectively) were recorded with a JEOL
157.0 (C=N). MS, m/z (I (%)): 285 [M] (8), 268 [M – OH]
rel
(13), 253 [M – CH OH] (6), 236 (8), 165 [C H O] (100), 150
3 11 17
+
+
4
+
+
JNMꢀECX400 spectrometer, the chemical shifts are given in the
δ scale relative to SiMe4 (inner standard). Elemental analysis
was performed with a Euro Vector EAꢀ3000 CHNS analyzer.
Melting points were measured in capillaries using PTPꢀM appaꢀ
ratus. Thin layer chromatography was performed with Silufol
UVꢀ254 plates, the spots were visualized by UV light and iodine
vapors. Dimeric nitroso chlorides 1a—c and chloro oxime 1d
were synthesized by the known procedures.1
[C H O] (4), 133 (6), 129 (7), 105 (9), 103 (12), 91 (28) [C H ] .
10 14 7 7
Found (%): C, 75.58; H, 8.01; N, 4.81. C H NO . Calculated
18
23
2
(%): C, 75.76; H, 8.12; N, 4.91.
2ꢀ(Propynꢀ2ꢀylꢀ1ꢀoxy)adamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime
(2e). Yield 76%, m.p. 124—126 °C. IR, ν/cm– : 3310, 3271 (OH);
2908, 2862 (CHAd); 2125 (C≡C); 1458, 1450, 1377, 1103, 1083,
1
1
1072, 1053, 933, 922, 887, 748, 663. H NMR (CD CN), δ: 1.50
3
8,21
(d, 2 H, HAd, J = 11.9 Hz); 1.66—1.80 (m, 8 H, HAd); 2.04 (br.s,
Synthesis of αꢀalkoxy oximes 2a—e (general procedure). To
a suspension of sodium carbonate (5 g) in MeOH (50 mL) or
propargyl alcohol (for 2e), dimeric nitroso chloride 1a—c (5 mmol)
or 1ꢀ(2ꢀchloroadamantꢀ2ꢀyl)ꢀNꢀhydroxyꢀ1ꢀphenylmethane imiꢀ
ne 1d was added portionwise over 5 min at 55—65 °C. The mixture
was heated for 30 min, cooled, and poured into cold water
2 H, HAd); 2.13 (d, 2 H, HAd, J = 12.4 Hz); 2.34 (t, 1 H, C≡CH,
4
4
J = 2.3 Hz); 3.92 (d, 2 H, CH O, J = 2.3 Hz); 6.95 (s, 1 H,
2
3
1
CH=N); 8.49 (br.s, 1 H, OH). C NMR (CD CN), δ: 27.2 and
3
27.4 (C(5)HAd, C(7)HAd); 32.2 (2 (CH2)Ad); 33.1 (2 (CH ) );
2 Ad
34.2 (C(1)HAd, C(3)HAd); 37.7 (H C(6) ); 49.5 (CH O); 75.5
2
Ad
2
(C≡CH); 79.5 (CAd(2)); 81.1 (C≡CH); 151.4 (CH=N). Found
(
300 mL) with stirring. The precipitate formed was collected by
filtration, washed with water, and recrystallized from MeOH.
ꢀMethoxyadamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime (2a). Yield
(%): C, 71.83; H, 8.10; N, 5.80. C H NO . Calculated (%):
C, 72.07; H, 8.21; N, 6.00.
14
19
2
2
Synthesis of αꢀazido oximes 3a,b (general procedure). To
a suspension of sodium azide (0.65 g, 10 mmol) in MeOH
(10 mL), 15ꢀcrownꢀ5 (0.1 g) was added followed by portionwise
addition of 1ꢀ(2ꢀchloroadamantꢀ2ꢀyl)ꢀNꢀhydroxyꢀ1ꢀphenylꢀ
methane imine (1d) (1.45 g, 5 mmol) or dimeric 2ꢀchloroꢀ2ꢀ
(nitrosomethyl)adamantane (1a) (1.07 g, 2.5 mmol) at 65 °C.
The solution was stirred for 20 min, cooled, and poured into cold
water (100 mL). The precipitate formed was collected by filtraꢀ
tion, washed with water, and recrystallized from MeOH.
–
1
9
2
8
1
7
2
1
1%, m.p. 105—107 °C. IR, ν/cm : 3400—3200 (OH); 2905,
851 (CHAd); 1450, 1423, 1354, 1300, 1080, 1045, 984, 941, 906,
1
33, 748. H NMR (CDCl ), δ: 1.51—1.56 (m, 2 H, HAd); 1.67—
3
.80 (m, 8 H, HAd); 2.10 (br.s, 4 H, HAd); 3.13 (s, 3 H, CH O);
3
.08 (s, 1 H, CH=N); 8.81 (s, 1 H, OH). 1 C NMR (CDCl ), δ:
3
3
7.1, 27.5, 32.2, 32.9, 34.2, 37.7, 48.9 (CH O), 78.8 (C (2)),
3
Ad
+
52.9 (C=N). MS, m/z (Irel (%)): 192 (100) [M – OH] , 179
30), 177 (34), 165 (42) [M – CH NO] , 160 (41), 133 (15), 105
16), 91 (54) [C H ] . Found (%): C, 68.71; H, 9.00; N, 6.55.
+
(
(
2
+
2ꢀAzidoadamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime (3a). Yield
91%, m.p. 180—182 °C (decomp.). IR, ν/cm– : 3400—3100
(OH); 2905, 2858 (CH ); 2087 (N ); 1454, 1234, 1065, 957,
7
7
1
C H NO . Calculated (%): C, 68.87; H, 9.15; N, 6.69.
12
19
2
1
ꢀ(2ꢀMethoxyadamantꢀ2ꢀyl)ethanone (E)ꢀoxime (2b). Yield
Ad
3
–
1
1
8
2%, m.p. 148—150 °C. IR, ν/cm : 3400—3200 (OH); 2905,
933, 756, 706. H NMR (CDCl ), δ: 1.64 (d, 2 H, HAd, J =
3
2
851 (CHAd); 1450, 1362, 1080, 1049, 984, 941, 895, 737.
= 12.1 Hz); 1.70—1.90 (m, 8 H, HAd); 2.12—2.21 (m, 4 H,
HAd); 7.38 (s, 1 H, CH=N); 8.05 (br.s, 1 H, OH). C NMR
1
13
H NMR (CDCl ), δ: 1.54 (d, 2 H, HAd, J = 12.1 Hz); 1.66—
3
1
.72 (m, 4 H, HAd); 1.81 (br.s, 7 H, 4 HAd, CH ); 2.11 (d, 2 H,
(CDCl ), δ: 27.0, 27.1, 32.7, 33.5, 33.9, 37.5, 68.1 (CAd(2));
3
3

Nitroso chlorides of adamantane series
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 10, October, 2015
2457
+
+
1
–
52.3 (C=N). MS, m/z (I (%)): 178 [M – N ] (100), 177 [M –
86 [C H NO] (48). Found (%): C, 69.92; H, 9.00; N, 10.43.
rel
3
4
8
+
+
HN3] (26), 175 (17), 129 (11), 91 (24) [C H ] , 79 (49).
C H N O . Calculated (%): C, 68.15; H, 9.15; N, 10.60.
15 24 2 2
7
7
Found (%): C, 59.80; H, 7.20; N, 25.31. C H N O. Calculated
1ꢀ[2ꢀ(Morpholinꢀ4ꢀyl)adamantꢀ2ꢀyl]ethanone (E)ꢀoxime
(4d). Yield 79%, m.p. 173—175 °C (decomp.). IR, ν/cm :
3400—3100 (OH); 2935, 2908, 2851, 2816, 1450, 1358, 1288,
1273, 1242, 1119, 995, 980, 933, 903, 868, 733. 1H NMR
1
1
16
4
–
1
(
%): C, 59.98; H, 7.32; N, 25.44.
2ꢀAzidoadamantꢀ2ꢀyl)(phenyl)methanone (E)ꢀoxime (3b). Yield
5%, m.p. 167—169 °C (decomp.). IR, ν/cm : 3400—3200 (OH);
(
–1
9
2
8
1
924, 2854 (CHAd); 2091 (N ); 1470, 1447, 1242, 1099, 980, 941,
(CDCl ), δ: 1.46 (d, 2 H, HAd, J = 11.5 Hz); 1.65—1.85 (m, 11 H,
3
3
1
79, 833, 764, 714. H NMR (CDCl ), δ: 1.59—1.69 (m, 6 H, HAd);
8 HAd, CH ); 2.16—2.24 (m, 4 H, HAd); 2.35 (br.s, 2 H, Hmorph);
3
3
.86—1.95 (m, 4 H, HAd); 2.12—2.15 (m, 4 H, HAd); 7.37—7.46
2.71 (d, 2 H, Hmorph, J = 10.8 Hz); 3.51—3.56 (m, 2 H, Hmorph);
3.79 (d, 2 H, Hmorph, J = 10.6 Hz); 8.69 (s, 1 H, OH). 13C NMR
(CDCl ), δ: 12.5 (CH ); 27.0, 27.2, 29.9, 31.9, 34.1, 37.9, 45.5
(
m, 5 H, Ph); 7.95 (s, 1 H, OH). 13C NMR (CDCl ), δ: 26.8, 27.0,
3
32.1, 33.0, 34.0, 37.5, 71.9 (CAd(2)); 128.1 (2 CHPh); 128.6 (2 CHPh);
3
3
1
28.9 (CHPh); 130.8 (CPh); 158.1 (C=N). MS, m/z (I (%)): 296
(2 CH N); 65.7 (C (2)); 68.3 (2CH O); 156.4 (C=N). Found
2 Ad 2
(%): C, 68.93; H, 9.36; N, 9.97. C H N O . Calculated (%):
16 26 2 2
rel
+
+
+
[M] , 267 (22), 254 [M – N ] (45), 251 [M – OH – N ] (82),
3
2
+
236 (43), 223 (34), 148 [C H N] (100), 131 (26), 121 (31), 104
C, 69.03; H, 9.41; N, 10.06.
1ꢀ[2ꢀ(Morpholinꢀ4ꢀyl)adamantꢀ2ꢀyl]propanꢀ1ꢀone (E)ꢀoxime
10
14
+
+
+
(55), 91 [C H ] (60), 79 [C H ] (81), 77 [C H ] (73). Found
7 7 6 7 6 5
–1
(%): C, 68.75; H, 6.68; N, 18.01. C H N O. Calculated (%):
(4e). Yield 85%, m.p. 169—171 °C (decomp.). IR, ν/cm : 3400—
17
20
4
C, 68.89; H, 6.80; N, 18.90.
3100 (OH); 2932, 2851, 2812, 1447, 1358, 1269, 1122, 1072, 995,
1
Synthesis of αꢀamino oximes 4a—g (general procedure). To
dimeric nitroso chloride 1a—c (2.5 mmol), the corresponding amine
or 1,1ꢀdimethylhydrazine (5 mL) was added. The resulting suspenꢀ
sion was heated with stirring at 80—90 °C for 10 min until complete
dissolution of the starting dimer and disappearance of blue color of
the solution. The reaction mixture was poured into cold water
933, 89, 872, 833, 806, 744. H NMR (CDCl ), δ: 1.24 (t, 3 H,
3
CH CH , J = 7.3 Hz); 1.46 (d, 2 H, HAd, J = 11.9 Hz); 1.60—1.83
2
3
(m, 8 H, HAd); 2.16—2.27 (m, 6 H, 4 HAd, CH CH ); 2.35 (br.s,
2
3
2 H, Hmorph); 2.71 (d, 2 H, Hmorph, J = 10.5 Hz); 3.52—3.55 (m, 2 H,
morph); 3.78 (d, 2 H, Hmorph, J = 10.6 Hz); 8.27 (s, 1 H, OH).
H
13
C NMR (CDCl ), δ: 10.8 (CH CH ); 20.6 (CH CH ); 27.3 (2 C);
3
3
2
3
2
(
100 mL). The precipitate formed was collected by filtration, washed
30.1, 32.2, 34.3, 38.0, 45.6 (2 CH N); 66.5 (C (2)); 68.3 (2 CH O);
2 Ad 2
+
+
with water, and recrystallized from MeOH.
160.9 (C=N). MS, m/z (I (%)): 292 (1) [M] , 275 [M – OH]
rel
+
2
ꢀ(Piperidinꢀ1ꢀyl)adamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime
(22), 220 [M – CH NO] (100), 207 (36), 206 (22), 190 (33), 150
2
–
1
+
+
+
(
4a). Yield 86%, m.p. 179—181 °C (decomp.). IR, ν/cm
:
[C H O] (10), 91 (12) [C H ] , 86 [C H NO] (13). Found
10 14 7 7 4 8
3
1
400—3200 (OH); 2970, 2910, 2849, 2802, 1468, 1447, 1354,
(%): C, 69.66; H, 9.57; N, 9.45. C H N O . Calculated (%):
17 28 2 2
1
298, 1285, 1204, 1153, 1101, 993, 939, 743. H NMR (CDCl ),
C, 69.83; H, 9.65; N, 9.58.
2ꢀ(Benzylamino)adamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime (4f).
3
δ: 1.38—1.45 and 1.59—1.81 (both m, 16 H, 14 HAd, 2 Hpyp)*;
.99 (t, 2 H, Hpyp, J = 11.2 Hz); 2.25 (br.s, 4 H, Hpyp); 3.01 (d, 2 H,
–
1
1
Yield 95%, m.p. 128—130 °C (decomp.). IR, ν/cm : 3300—
H
pyp, J = 10.1 Hz); 7.21 (s, 1 H, CH=N); 7.76 (br.s, 1 H, OH).
3100 (OH); 2935, 2889, 2851 (CHAd); 1605, 1497, 1466, 1447,
13
1
C NMR (CDCl ), δ: 25.4, 27.2, 27.3, 27.6, 31.2, 31.4, 34.0,
1354, 1296, 1219, 1115, 926, 887, 752. H NMR (CDCl ), δ:
3
3
3
8.0, 45.1, 62.6 (C (2)); 154.6 (C=N). MS, m/z (I (%)): 262
1.27 (br.s, 1 H, NH); 1.59 (d, 2 H, HAd, J = 12.1 Hz); 1.71—1.77
(m, 4 H, HAd); 1.88—2.00 (m, 6 H, HAd); 2.35 (d, 2 H, HAd, J =
Ad
rel
+
+
[
M] (3), 245 [M – OH] (48), 243 (8), 230 (5), 218 [M –
+
+
+
–
CH NO] (100), 162 (15), 91 [C H ] (9), 84 [C H N]
= 12.1 Hz); 3.63 (s, 2 H, CH N); 7.20 (s, 1 H, CH=N); 7.25—
2
7
7
5
10
2
+
13
(
65), 79 [C H ] (8). Found (%): C, 73.11; H, 9.93; N, 10.52.
7.40 (m, 5 H, Ph); 8.51 (br.s, 1 H, OH). C NMR (CDCl ), δ:
6
7
3
C H N O. Calculated (%): C, 73.24; H, 9.99; N, 10.68.
27.5, 27.9, 32.0, 33.6, 34.0, 38.2, 45.3 (CH N); 60.3 (CAd(2));
16
26
2
2
1
ꢀ[2ꢀ(Piperidinꢀ1ꢀyl)adamantꢀ2ꢀyl]ethanone (E)ꢀoxime (4b).
126.9 and 128.4 (5 CHPh); 141.1 (C ); 155.3 (C=N). MS, m/z
Ph
–
1
+
+
Yield 89%, m.p. 200—202 °C (decomp.). IR, ν/cm : 3400—
100 (OH); 2951, 2901, 2847, 2808, 1447, 1366, 1223, 1099,
80, 949, 930, 903, 860, 729. H NMR (CDCl ), δ: 1.38—1.44
(Irel (%)): 267 [M – OH] (53), 240 [M – CH NO] (36), 239
2
+
+
3
9
(19), 238 (17), 193 (5), 162 (20), 106 [C H N] (46), 91 [C H ]
7 8 7 7
1
(100). Found (%): C, 75.84; H, 8.37; N, 9.71. C H N O. Calꢀ
3
18 24 2
and 1.59—1.81 (both m, 21 H, 14 HAd, 4 Hpyp, CH ); 2.24 (d, 2 H,
culated (%): C, 76.02; H, 8.51; N, 9.85.
2ꢀ(2,2ꢀDimethylhydrazino)adamantaneꢀ2ꢀcarbaldehyde (E)ꢀ
oxime (4g). Yield 75%, m.p. 139—141 °C (decomp.). IR, ν/cm :
3
Hpyp, J = 11.7 Hz); 2.39 (br.s, 2 H, Hpyp); 2.98 (d, 2 H, Hpyp, J =
10.3 Hz); 8.55 (br.s, 1 H, OH). 13C NMR (CDCl ), δ: 12.3
–1
=
3
(
(
CH ); 25.6, 27.1, 27.4, 27.6, 30.4, 32.1, 34.3, 38.0, 46.0, 66.1
CAd(2)); 157.1 (C=N). Found (%): C, 73.75; H, 10.10; N, 10.03.
3240, 3175, 3094 (NH, OH); 2955, 2905, 2851 (CHAd); 1466,
1447, 1354, 1246, 1107, 995, 940, 868, 833, 748. 1H NMR
3
C H N O. Calculated (%): C, 73.87; H, 10.21; N, 10.13.
(CDCl ), δ: 1.46 (d, 2 H, HAd, J = 12.1 Hz); 1.65—2.00 (m, 10 H,
17
28
2
3
2
ꢀ(Morpholinꢀ4ꢀyl)adamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime
HAd); 2.31 (d, 2 H, HAd, J = 12.1 Hz); 2.42 (s, 6 H, 2 CH ); 7.28
3
–
1
(
4c). Yield 80%, m.p. 142—144 °C (decomp.). IR, ν/cm
400—3100 (OH); 2957, 2912, 2885, 2845, 2814, 1450, 1310,
286, 1269, 1117, 1001, 935, 868, 746. H NMR (CDCl ), δ:
.42 (d, 2 H, HAd, J = 11.9 Hz); 1.66—1.84 (m, 8 H, HAd); 2.18
:
(s, 1 H, CH=N); 8.08 (br.s, 2 H, OH, NH). MS, m/z (I (%)):
rel
+
+
+
3
1
1
237 [M] (3), 192 [M – CH NO] (7), 178 (3), 91 [C H ] (7),
3 7 7
1
59 (100). Found (%): C, 65.60; H, 9.69; N, 17.63. C H N O.
3
13 23 3
Calculated (%): C, 65.79; H, 9.77; N, 17.70.
(
(
2
8
3
br.s, 2 H, HAd); 2.23 (d, 2 H, HAd, J = 11.9 Hz); 2.30—2.45
m, 2 H, Hmorph)*; 2.67—2.78 (m, 2 H, Hmorph); 3.47—3.60 (m,
2ꢀ{2ꢀ[(E)ꢀ(Hydroxyimino)methyl]adamantꢀ2ꢀyl}hydrazinꢀ
ecarboxamine (4h). To a solution of dimeric 2ꢀchloroꢀ2ꢀ
(nitrosomethyl)adamantane 1a (1.07 g, 2.5 mmol) in pyridine
(10 mL), semicarbazide (0.45 g, 6 mmol) was added and the
resulting mixture was heated with stirring at 80—90 °C (water
bath) for 20 min. The reaction mixture was poured into cold
water (100 mL). The precipitate formed was collected by filtraꢀ
H, Hmorph); 3.76—3.88 (m, 2 H, Hmorph); 7.21 (s, 1 H, CH=N);
.06 (s, 1 H, OH). 13C NMR (CDCl ), δ: 27.2, 27.4, 30.8, 31.3,
3
3.8, 37.9, 44.6 (2 CH N); 62.2 (CAd(2)); 68.0 (2 CH O); 153.7
2
2
+
+
(
2
C=N). MS, m/z (I (%)): 264 [M] (3), 247 [M – OH] (48),
rel
20 [M – CH NO] (100), 179 (18); 162 (34), 91 [C H ] (15),
+
+
2
7
7
*
Hpyp is Hpiperidinyl
.
* Hmorph is Hmorpholinyl.

2
458
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 10, October, 2015
Krasnikov et al.
tion, washed with water, and recrystallized from MeOH. Yield
2ꢀAdamantyl(phenyl)methanone (Z)ꢀoxime (5c). Yield 79%,
.15 g (91%), m.p. 243—245 °C (decomp.). IR, ν/cm–1: 3491,
329, 3236 (OH, NH); 2901, 2854 (CHAd); 1663 (C=O); 1566,
466, 1408, 1308, 1246, 1107, 933, 906, 883, 833. 1H NMR
m.p. 218—220 °C. IR, ν/cm : 3269 (OH); 2920, 2858 (CH );
–1
1
3
1
Ad
1
1452, 1443, 1358, 1099, 972, 945, 883, 833, 764, 721, 698. H
NMR (CDCl ), δ: 1.62 (d, 2 H, HAd, J = 12.2 Hz); 1.70—1.90
3
(
(
DMSOꢀd ), δ: 1.43 (d, 2 H, HAd, J = 11.6 Hz); 1.60—1.85
m, 10 H, HAd); 2.29 (d, 2 H, HAd, J = 11.2 Hz); 4.74 (s, 1 H,
(m, 8 H, HAd); 2.02 (br.s, 2 H, HAd); 2.07 (d, 2 H, HAd, J =
6
= 12.8 Hz); 2.84 (s, H, HAd(2)); 7.25—7.29 (m, 2 H, Ph); 7.33—
13
NH); 5.85—6.10 (m, 3 H, NH, NH ); 7.08 (s, 1 H, CH=N);
1
7.43 (m, 3 H, Ph); 8.11 (br.s, 1 H, OH). C NMR (CDCl ), δ:
2
3
0.70 (br.s, 1 H, OH). MS, m/z (I (%)): 252 [M]+ (3), 234
27.9 and 28.1 (C(5)HAd, C(7)HAd); 29.5 (C(1)HAd, C(3)HAd);
rel
+
+
[
M – H O] (2), 208 [M – CH NO] (6), 207 (10), 206 (10),
2 2
32.4 (2 (CH ) ); 37.8 (H C(6)Ad); 38.8 (2 (CH ) ); 49.8
2 Ad
2
2 Ad
+
1
1
91 (11), 189 (9), 178 [M – CH N O] (100), 164 (46), 163 (45),
(C(2)HAd); 127.4 (2 CHPh); 128.3 (2 CHPh); 128.4 (CHPh); 134.0
(CPh); 161.2 (C=N). Found (%): C, 79.89; H, 8.20; N, 5.42.
4
3
+
61 (36), 150 [C H O] (15), 119 (19), 106 (27), 91 (43)
10
14
+
[
C H ] . Found (%): C, 56.85; H, 7.85; N, 21.98. C H N O .
C H NO. Calculated (%): C, 79.96; H, 8.29; N, 5.49.
7
7
12 20
4
2
17 21
Calculated (%): C, 57.12; H, 7.99; N, 22.21.
2ꢀAminoadamantꢀ2ꢀyl)(phenyl)methanone (E)ꢀoxime (4i). To
ꢀ(2ꢀchloroadamantꢀ2ꢀyl)ꢀNꢀhydroxyꢀ1ꢀphenylmethane imine
1d) (1 g, 3.5 mmol), dichloromethane (10 mL) and 25% aqueꢀ
ous ammonia (5 mL) were added, and the mixture was stirred for
h at room temperature. The organic layer was separated, washed
with water, dried with Na SO , and the volatiles were removed
(
This work was financially supported by the Ministry of
Education and Science of the Russian Federation within
the framework of the state assignment in the field of scienꢀ
tific research (4.1597.2014/K).
1
(
2
2
4
References
in vacuo. The residue was recrystallized from MeOH. Yield 0.78
g (83%), m.p. 174—176 °C (decomp.). IR, ν/cm–1: 3402, 3321,
3
1
294 (OH, NH ); 3059, 2908, 2858 (CHAd); 1639, 1601, 1427,
1. P. P. Kadzyauskas, N. S. Zefirov, Russ. Chem. Rev., 1968,
37, 543.
2
1
358, 945, 705. H NMR (DMSOꢀd ), δ: 1.39 (d, 2 H, HAd, J =
6
=
8
12.6 Hz); 1.48 (d, 2 H, HAd, J = 12.4 Hz); 1.57, 1.70—1.79 (s, m,
2. I. M. Lyapkalo, S. L. Ioffe, Russ. Chem. Rev., 1998, 67, 467.
3. E. Francotte, R. Merenyi, B. VandenbulckeꢀCoyette, H.ꢀG.
Viehe, Helv. Chim. Acta, 1981, 64, 1208.
4. T. L. Gilchrist, Chem. Soc. Rev., 1983, 12, 53.
5. P. S. Chauhan, S. M. Weinreb, J. Org. Chem., 2014, 79,
6389.
H, 6 HAd, NH ); 1.97 (d, 2 H, HAd, J = 11.9 Hz); 2.22 (d, 2 H,
2
HAd, J = 11.9 Hz); 7.23—7.31 (m, 3 H, Ph); 7.41 (dd, 2 H, Ph, J =
8.2 Hz, J = 1.6 Hz); 10.37 (s, 1 H, OH). 13C NMR (DMSOꢀd ),
=
6
δ: 27.4 (C(5)HAd, C(7)HAd); 32.4 (2 (CH2)Ad); 34.7 (2 (CH ) );
2 Ad
3
4.9 (C(1)HAd, C(3)HAd); 38.4 (CH (6)Ad); 60.3 (CAd(2)); 127.7
2
(
(
1
2 CHPh); 127.8 (CHPh); 129.5 (2 CHPh); 134.0 (CPh); 161.2
6. S. C. C. Nunes, S. M. M. Lopes, C. S. B. Gomes, A. Lemos,
A. A. C. C. Pais, T. M. V. D. Pinho e Melo, J. Org. Chem.,
2014, 79, 10456.
+
C=N). MS, m/z (I (%)): 269 [M – 1] (1), 253 (21), 151 (19),
rel
+
50 [C H O] (100), 133 (10), 91 (13). Found (%): C, 75.39;
10
14
H, 8.08; N, 10.28. C H N O. Calculated (%): C, 75.52;
H, 8.20; N, 10.36.
7. O. Miyata, T. Miyoshi, M. Ueda, ARKIVOC, 2013, Part ii, 60.
8. Y. Zhang, D. Stephens, G. Hernandez, R. Mendoza, O. V.
Larionov, Chem. Eur. J., 2012, 18, 16612.
1
7
22
2
Reduction of nitroso chlorides with sodium cyanoborohydride
(
1
general procedure). To a stirred suspension of NaBH CN (0.94 g,
5 mmol) in DMF (15 mL), nitroso compound 1a,c,d (5 mmol)
9. T. C. Wabnitz, S. Saaby, K. A. Jшrgensen, Org. Biomol.
Chem., 2004, 2, 828.
3
was added at 80 °C. After 20 min, the mixture was cooled to
room temperature and poured into cold water (150 mL). The
precipitate formed was collected by filtration, washed with waꢀ
ter, and recrystallized from MeOH.
10. S. E. Denmark, M. S. Dappen, J. Org. Chem., 1984, 49, 799.
11. P. Ciattoni, L. Rivolta, Chim. Ind. (Milan), 1967, 49, 1186.
12. W. Hobold, U. Prietz, W. Pritzkow, J. Prakt. Chem., 1969,
311, 260.
Adamantaneꢀ2ꢀcarbaldehyde (E)ꢀoxime (5a). Yield 83%, m.p.
13. K. Weiser, A. Berndt, Angew. Chem., Int. Ed., 1975, 14, 70.
14. C. E. Griffin, R. N. Haszeldine, J. Chem. Soc., 1960, 1398.
15. P. E. Krasnikov, E. A. Sidnin, V. A. Osyanin, Yu. N. Klimoꢀ
chkin, Chem. Heterocycl. Compd. (Engl. Transl.), 2014, 50,
1090 [Khim. Geterotsikl. Soedin., 2014, 50, 1183].
16. E. V. Golovin, O. V. Golovina, G. A. Guseva, N. N.
Malґkova, Yu. N. Klimochkin, Izv. Vyssh. Uchebn. Zaved.
Khim. Khim. Technol., 2005, 48, No. 10, 65 (in Russian).
17. P. E. Krasnikov, Yu. N. Klimochkin, Butlerov Commun.,
2012, 31, 15 (in Russian).
–1
1
1
=
7
43—145 °C. IR, ν/cm : 3257, 3163 (OH); 2901, 2891 (CHAd);
1
448, 1306, 933, 723. H NMR (CDCl ), δ: 1.62 (d, 2 H, HAd, J =
3
12.2 Hz); 1.74—2.03 (m, 12 H, HAd); 2.59 (br.s, 1 H, HAd(2));
.59 (d, 1 H, CH=N, J = 5.5 Hz); 7.97 (br.s, 1 H, OH). 13C NMR
CDCl ), δ: 27.7 and 27.8 (C(5)HAd, C(7)HAd); 31.2 (C(1)HAd
(
,
3
C(3)HAd); 32.5 (2 (CH ) ); 37.7 (H C(6)Ad); 38.3 (2 (CH ) );
2 Ad
2
2 Ad
4
4.8 (C(2)HAd); 155.6 (C=N). Found (%): C, 73.59; H, 9.50;
N, 7.70. C H NO. Calculated (%): C, 73.70; H, 9.56; N, 7.81.
11
17
1
ꢀ(2ꢀAdamantyl)propanꢀ1ꢀone (E)ꢀoxime (5b). Yield 89%,
–
1
m.p. 153—155 °C. IR, ν/cm : 3228 (OH); 2970 (CHAd); 1450,
099, 953, 933, 752. H NMR (CDCl ), δ: 1.08 (t, 3 H, CH CH ,
18. P. E. Krasnikov, PhD Thes. (Chem.), Samarsk. State Techꢀ
nol. Univ., Samara, 2013, 155 pp.
1
1
3 2 3
J = 7.8 Hz); 1.56 (d, 2 H, HAd, J = 12.6 Hz); 1.72 (br.s, 1 H,
19. C. A. Grob, Angew. Chem., 1969, 8, 535.
HAd); 1.76—1.82 (m, 4 H, HAd); 1.88—1.91 (m, 3 H, HAd); 1.98
20. K. Prantz, J. Mulzer, Chem. Rev., 2010, 110, 3741.
21. P. E. Krasnikov, E. A. Sidnin, V. A. Osyanin, Yu. N. Klimoꢀ
chkin, Russ. J. Org. Chem. (Engl. Transl.), 2015, 51, 325 [Zh.
Org. Khim., 2015, 51, 343].
(
d, 2 H, HAd, J = 12.2 Hz); 2.20 (br.s, 2 H, HAd); 2.34 (q, 2 H,
CH CH , J = 7.8 Hz); 2.48 (s, 1 H, HAd(2)); 8.74 (br.s, 1 H,
2
3
13
OH). C NMR (CDCl ), δ: 10.8 (CH CH ); 20.0 (CH CH );
3
3
2
3
2
2
8.0 and 28.1 (C(5)HAd, C(7)HAd); 29.5 (C(1)HAd, C(3)HAd);
3
2.7 (2 (CH2)Ad); 37.8 (H C(6)Ad); 39.1 (2 (CH ) ); 49.0
2
2 Ad
(
C(2)HAd); 163.9 (C=N). Found (%): C, 75.21; H, 10.11;
Received February 8, 2015;
in revised form May 12, 2015
N, 6.72. C H NO. Calculated (%): C, 75.32; H, 10.21; N, 6.76.
13
21