Cyclotransformation of azinium salts into hydrogenated cyclic alkylamino ketones

Article abstract of DOI:10.1007/s10593-005-0316-z

A study was carried out on the nucleophilic cyclotransformation of pyrrolo[1,2-a]pyrazinium salts and isoquinolinium salts containing a methyl group in the α-position. A method for the preparation of alkylaminotetrahydroindolizinones and tetralones was pr

Full text of DOI:10.1007/s10593-005-0316-z

Chemistry of Heterocyclic Compounds, Vol. 41, No. 10, 2005
CYCLOTRANSFORMATION OF
AZINIUM SALTS INTO HYDROGENATED
CYCLIC ALKYLAMINO KETONES
V. I. Terenin and A. S. Ivanov
A study was carried out on the nucleophilic cyclotransformation of pyrrolo[1,2-a]pyrazinium salts and
isoquinolinium salts containing a methyl group in the α-position. A method for the preparation of
alkylaminotetrahydroindolizinones and tetralones was proposed.
Keywords: isoquinoline, pyrrolo[1,2-a]pyrazine, 5,6,7,8-tetrahydroindolizinone, α-tetralone,
nucleophilic rearrangement.
The isomerizational recyclization of azinium salts by the action of nucleophiles known as the Kost–
Sagitullin rearrangement involves the exchange of the exocyclic α-carbon atom by a ring nitrogen atom [1].
Heterocycles undergoing cyclotransformation through the ANRORC mechanism form either aromatic or
conjugated cyclic structures [2]. The exocyclic carbon atom must have at least two hydrogen atoms required for
consecutive reduction of aromaticity of the transformation products, which are either carbocycles or
heterocycles. In previous work, we have shown that pyrrolo[1,2-a]pyrazinium alkyl iodides containing
methylene group at position 1 are converted by the action of alcoholic alkylamines into 8-alkylaminoindolizines
[3], while isoquinolinium alkyl iodides are converted to 1-alkylaminonaphthalenes [4]. The nucleophilic
transformation of azacycles containing an α-methine substituent was not examined due to the above reasons. We
are the first to discover the capacity of aromatic heterocyclic compounds 2a-f and 5a-c containing a methine
substituent at the α-position relative to the cyclic nitrogen atom to undergo a previously unreported
cyclotransformation to give hydrogenated cyclic alkylamino ketones 3a-g and 6a-c, including spirocyclic
compounds.
1
A comparative analysis of the H NMR spectra of nitrogenous bases 1a-c, 4a,b and cyclotransformation
products 3a-g and 6a-d revealed clear structural features of these compounds. The disappearance of the signals
of the protons of the pyrazine system in the case of starting 1a-c and the pyridine system in the case of 3a and 3b
as well as of the methine hydrogen atom and the appearance of signals of diastereotopic protons in the resonance
range of aliphatic groups protons indicates recyclization of the starting azacycles. The structures of 3b and 6b
1
3
were also supported by C NMR spectroscopy. The IR spectra of the products show C=O and NH group
stretching bands.
Variation in the reaction temperature and duration in the reaction of alcoholic solutions of alkylamines
with pyrrolo[1,2-a]pyrazinium salts 2 hardly affects the yield of the recyclization products. The reactions with
isoquinolinium salts 5 proceed somewhat differently. The ratio of the products of dealkylation 4a and
recyclization 6a in the case of the reaction of 1-isopropyl-2-methylisoquinolinium iodide (5a) with ethanolic
_
_________________________________________________________________________________________
M. V. Lomonosov Moscow State University, 119899 Moscow, Russia; e-mail: vter@org.chem.msu.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1551-1557, October, 2005. Original
article submitted March 16, 2005.
1
300
0009-3122/05/4110-1300©2005 Springer Science+Business Media, Inc.

R
R
R2 I
3
H NR
R1
2
N
R
R1
N
R
+
N
N
_
I
R2
1
a–c
2
a–f
2
1
8
a
4
N
O
R
R1
Ha
Hb
3
8
5
7
6
R
NHR3
3
a–g
Com-
pound
1
2
Com-
pound
1
3
R
R
R
R
R
R
1
1
a
Me
Me
H
3a
3b
3c
3d
3e
3f
Me
Me
Me
Me
Me
H
H
H
Me
Et
b
Me
H
1
c
R+R = (CH
Me
2
)
4
i-Pr
Me
Et
2
2
a
H
Me
Me
Me
H
b
Me
H
Et
2
c
Me
Me
Me
H
Me
Et
R+R = (CH
R+R = (CH
2
)
)
4
Me
Et
2
d
Me
3g
2
4
H
2
e
R+R = (CH
R+R = (CH
2
)
)
4
Me
Et
2
f
2
4
H
Ha
Hb
3
4
5
NHR3
R
4
a
6
7
R2 I
H NR3
2
+
2
N
R
N
1
R2
8a
8
I
R
O
R
R
R
4
a,b
5a–c
6a–d
Com-
pound
2
Com-
pound
3
R
R
R
R
4
a
Me
6a
6b
6c
6d
Me
Me
Me
Me
4
b
R+R = (CH
Me
2
)
5
Et
5
a
Me
Et
i-Pr
Me
5
b
Me
2 5
R+R = (CH )
5
c
R+R = (CH
2
)
5
Me
solution of methylamine at 140 and 160°C is 1:2 and 5:1, respectively. The rates of the cyclotransformation and
dealkylation are probably similar at 140°C. The rate of the reaction leading to 1-isopropylisoquinoline (4a) at
1
60°C is greater than the rate of the competing recyclization reaction. In the reaction of 1-cyclohexyl-2-
methylisoquinolinium iodide (5c) with ethanolic solution of methylamine, it was found useful to carry out the
reaction at a lower temperature (120°C). This procedure probably takes advantage of the greater steric hindrance
produced by the cyclohexyl ring in comparison to the isopropyl group. Nevertheless, the yield of spirocyclic
product 5c remains low.
A study of the transamination of starting pyrrolo[1,2-a]pyrazinium alkyl iodides 2 and isoquinolinium
alkyl iodides 5 showed the feasibility of the complete exchange of the alkylamine fragment at C( in the
6)
2
resultant tetrahydroindolizinone derivatives 3 and at C(3) in tetralones 6. When R ≠ Me at the nitrogen atom in
3
the starting azinium salt and R ≠ Me in the alkylamine, the yields of the corresponding recyclization products
1
301

are reduced and the products of the dealkylation of the starting salts to give nitrogenous bases are enhanced. This
result is likely related to the steric hindrance of the bulky alkyl substituents in the starting salts and in the reagent
in the attack of the nucleophile at C in the starting heterocycle.
(
1)
This newly discovered reaction proceeds through the following scheme. Attack of the nucleophile at
α-carbon atom C(3) (pathway A) or C(1) (pathway B) in the case of a quaternary nitrogen atom leads to opening
of the heterocycle and formation of intermediates A1,3. Attack of the enamine fragment on the imine carbon of
intermediates B1-3 leads to formation of cyclic imines C1-3, which are then hydrolyzed to give hydrogenated
cyclic alkylamino ketones D1,2. Since the α-methine group contains only one hydrogen atom, aromatization is
impossible and recyclization ends with formation of the hydrogenated product. We should note that in the
reaction of the 1-isopropylpyrrolo[1,2-a]pyrazinium salt and ethanolic solution of isopropylamine, in addition to
6
-isopropylaminoindolizinone (3c), trace amounts of ketone D2 are formed as a consequence of reaction through
pathway B. Support for the scheme proposed below, we should add that a small amount of a mixture of imines
C2 and C1 (minor product) was isolated in the reaction of 1-isopropylpyrrolo[1,2-a]pyrazinium methyl
X
3
+
1
N
R2
3
R
NH2
3
R NH
2
R
R
(B)
(A)
NHR2
NHR3
NHR
3
X
X
X
3
R NH
2
NR3
NR2
NR
3
A2
A3
A1
R
R
R
R
R
R
~H+
H+
~H+
~
NR2
NR3
NR3
X
X
X
3
R NH
2
R
R
R
R
R
R
NHR3
NHR2
NHR3
B3
B1
B2
NHR3
NHR
2
NHR3
X
3
X
NH R
X
2
R
R
R
R
R
R
NR2
NR3
NR3
C1
C3
C2
+
H O
2
+
H O
+H O
2
2
3
2
3
–H NR
2
–
H NR
–H NR
2
2
NHR2
NHR3
X
X
R
R
R
R
O
D2
O
D1
Х = N or С
1
302

TABLE 1. Yields of Recyclization and Dealkylation Products
Yield of products, %
Starting
salt
Methylamine
Ethylamine
dealkylation
recyclization
dealkylation
recyclization
23
2
2
a
34
5*
15
17
3
19*
b
30
43
15
25
30
18
14
2
c
10
4
4*
12*
10*
2
2
4
3*
2
2
d
e
40
29
27
40
15
33
37
26
20
24
25
24
43
37
33
2
f
5
a
20
3
8
5*
*
35*
51*
2
2
5
b
18
7*
50
20
—
25
—
5
c
62*
_
*
*
______
Reaction was carried out at 120°C.
Reaction was carried out at 160°C.
2
1
iodide (2a) with ethanolic solution of ethylamine and these imines were detected by H NMR spectroscopy. In
addition to signals for the pyrrole ring protons, signals were found for the protons of two ethyl groups of imine
C2, while signals for protons of the methylimine and ethylamino groups were detected for the minor product, C1
(
see Experimental). In all likelihood, the initial attack of the nucleophile occurs at C(3) along with attack at α-
carbon atom C . However, we cannot evaluate the preference for nucleophilic attack at C or C(3) of the azine
(
1)
(1)
ring using the ratio of integral intensities of the protons in the abovementioned spectrum of imines C1 and C2
since intermediates A1 and B3 and imine C1 in the case of a large excess of alkylamine should undergo
transamination.
Such ring transformation is undoubtedly general in nature since it has been demonstrated for the
pyrrolo[1,2-a]pyrazine and isoquinoline systems and is a new method for the preparation of
tetrahydroindolizinones and tetralones, including spirocyclic products 3f,e, and 6c, containing an alkylamino
group.
EXPERIMENTAL
1
The H NMR spectra were taken on Varian VXR-400 and Bruker Ultra Shield spectrometers (400 MHz)
in CDCl at 28°C with TMS as the internal standard. The mass spectra were taken on a Kratos MS-90 mass
3
spectrometer at 70 eV ionization voltage. The IR spectra were taken on a UR-20 spectrometer in CCl . The
4
reaction course and purity of the products were checked by thin-layer chromatography on Alufol plates using
benzene and 1:1 benzene–ethyl acetate as eluents with development by iodine vapor and ethanolic ninhydrin.
Samples of starting pyrrolo[1,2-a]pyrazines 1a-c were prepared by our previous procedure [5], while
isoquinolines 4a,b were obtained according to the classical Bischler–Napieralski method [6] with subsequent
aromatization over palladium black.
Preparation of Salts 2a-f and 5a-c (General Method). A mixture of nitrogenous base 1a-c, 4a,b
(
3 mmol) and methyl iodide or ethyl iodide (3.5-4 ml) was heated for 2-3 h in a sealed ampule at 70-80°C until
the reaction mixture separated into two layers. The upper oily layer was separated and crystallized upon ice
1
303

cooling. The crystals were washed several times with cold acetone. The yield of 2a was 76%; mp 160-161°C.
The yield of 2b was 65%; mp 82-84°C. The yield of 2c was 72%; mp 163-165°C. The yield of 2d was 62%;
mp 84-86°C. The yield of 2e was 68%; mp 160-162°C. The yield of 2f was 52%; mp 123-124°C. The yield of
a was 80%; mp 240-241°C. The yield of 5b was 75%; mp 80-82°C. The yield of 5c was 45%; mp 171-172°C.
Preparation of Recyclization Products 3a-f and 6a-c (General Procedure). A mixture of quaternary
5
salt 2a-f or 5a-c (1 mmol) and 40% ethanolic alkylamine (4-5 ml) was heated in a sealed tube for 6-8 h at 140°C.
The solvent was removed in vacuum. The recyclization product was isolated by chromatography on a neutral
alumina column (Brockmann activity II) with elution using benzene and subsequent increase in polarity to 1:1
benzene–ethyl acetate.
1
H NMR Spectrum of Imine Mixture. A. C2 (6-Ethylamino-8-ethylimino-7,7-dimethyl-5,6,7,8-
tetrahydroindolizine), δ, ppm, (J, Hz): 1.08 (3H, t, J = 7.6, 6-NHCH
2
3
CH ); 1.21, 1.23 (both 3H, both s,
7
-(CH ) , 7-(CH ) ); 1.35 (3H, t, J = 7.4, 8-NCH CH ); 2.62, 2.79 (both 1H, both dq, J = 7.4, J = 11.5,
3
a
3 b
2
3
6
-NHCH H CH ); 2.88 (1H, dd, J = 4.2, J65a = 5.7, H-6); 3.61 (2H, m, 8-NCH H CH ); 3.97 (1H, dd,
a
b
3
65b
a
b
3
J5a5b = 12.0, J5a6 = 5.7, H -5); 4.20 (1H, dd, J
b 21
= 12.0, J5b6 = 4.2, H -5); 6.27 (1H, dd, J = 3.7, J = 2.4, H-2);
a
5b5a
6
.60 (1H, dd, J = 2.4, J = 1.1, H-1); 6.69 (1H, m, H-3).
12
B. C1 (Minor Component) (6-Ethylamino-7,7-dimethyl-8-methylimino-5,6,7,8-tetrahydro-
indolizine), δ, ppm, (J, Hz): 1.09 (3H, t, J = 7.4, 6-NHCH CH ); 1.21, 1.23 (both 3H, both s, 7-(CH
-(CH ) ); 2.63, 2.79 (both 1H, both dq, J = 7.4, J = 11.4, 6-NHCH H CH ); 2.87 (1H, dd, J = 4.2, J65a = 5.7,
3
3
3 a
) ,
7
3
b
a
b
3
65b
H-6); 3.45 (3H, s, 8-NCH ); 4.03 (1H, dd, J
5a5b
= 12.0, J5a6 = 5.7, Ha-5); 4.22 (1H, dd, J5b5a = 12.0, J5b6 = 4.2,
3
H -5); 6.30 (1H, dd, J = 3.7, J = 2.4, H-2); 6.72 (2H, m, H-1, H-3).
b
-
1
7
,7-Dimethyl-6-methylamino-5,6,7,8-tetrahydroindolizinone (3a). IR spectrum, ν, cm : 3340 (NH),
1
1
6
653 (C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.21, 1.31 (both 3H, both s, 7-(CH ) , 7-(CH ) ); 2.51 (3H, s,
3
a
3 b
-NHCH ); 2.96 (1H, dd, J65a = 6.9, J65b = 3.8, H-6); 4.05 (1H, dd, J5a5b = 12.9, J5a6 = 6.9, H -5); 4.32 (1H, dd,
3
a
J5b5a = 12.9, J5b6 = 3.8, H -5); 6.26 (1H, dd, J = 4.1, J = 2.2, H-2); 6.81 (1H, dd, J = 2.2, J = 1.5, H-3); 6.98
b
21
23
32
31
+
+
(
[
1H, dd, J = 4.1, J = 1.5, H-1). Mass spectrum, m/z (I , %): 192 [M] (18), 149 [M - CH(CH ) ] (27), 107
12 13 rel 3 2
+
+
M - C(CH ) CHNHCH ] (53), 98 [M - C H NO] (100). Found, %: C 68.68; H 8.11; N 14.40. C H N O.
3
2
3
5
3
11 16
2
Calculated, %: C 68.72; H 8.3; N 14.57.
-
1
6
-Ethylamino-7,7-dimethyl-5,6,7,8-tetrahydroindolizinone (3b). IR spectrum, ν, cm : 3340 (NH),
1
1
660 (C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.08 (3H, t, J = 7.1, 6-NHCH CH ); 1.17, 1.28 (both 3H, both
2
3
s, 7-(CH ) , 7-(CH ) ); 2.62, 2.81 (both 1H, both dq, J = 7.1, J = 11.2, 6-NHCH H CH ); 3.03 (1H, dd, J = 4.1,
3
a
3 b
a
b
3
65b
J65a = 7.5, H-6); 3.96 (1H, dd, J5a6 = 7.5, J5a5b = 12.7, H -5); 4.27 (1H, dd, J = 4.1, J5b5a = 12.7, H -5); 6.24
a
5b6
b
1
3
(
1H, dd, J = 2.2, J = 4.0, H-2); 6.79 (1H, t, J = 2.2, H-3); 6.96 (1H, dd, J = 2.2, J = 4.0, H-1). C NMR
21 12
spectrum without proton decoupling, δ, ppm, (J, Hz): 15.5 (q, J = 125.8, 6-NHCH CH ); 19.1 (q, J = 130.2,
2
3
7
-(CH ) ); 22.5 (q, J = 111.2, 7-(CH ) ); 42.9 (t, J = 130.2, 6-CH CH ); 45.6 (t, J = 142.0, C ); 45.7 (s, C );
3 a 3 b 2 3 (5) (7)
6
1.9 (d, J = 133.2, C ); 110.8 (ddd, J = 172.7, J = 7.3, J = 3.6, C ); 114.4 (ddd, J = 174.2, J = 7.3, J = 4.4,
(
6)
(1)
+
C ); 125.4 (dm, J = 184.4, C ); 128.7 (m, C ); 191.6 (s, C ). Mass spectrum, m/z (I , %): 206 [M] (12),
1
(
2)
(3)
(8a)
(8)
rel
+
+
63 [M - CH(CH ) ] (11), 112 [M - C H NO] (100). Found, %: C 68.68; H 8.81; N 13.53. C H N O.
3 2 5 3 12 18 2
Calculated, %: C 68.87; H 8.79; N 13.56.
-Isopropylamino-7,7-dimethyl-5,6,7,8-tetrahydroindolizinone (3c). IR spectrum, ν, cm : 3330
-
1
6
1
(
NH), 1640 (C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.03, 1.05 (both 3H, both d, J = 6.2, 6-NHCH(CH ) );
3
2
1
.18, 1.31 (both 3H, both s, 7-(CH ) , 7-(CH ) ); 2.92 (1H, m, 6-NHCH(CH ) ); 3.08 (1H, dd, J = 4.2,
3 a 3 b 3 2 65b
J65a = 8.2, H-6); 3.92 (1H, dd, J5a6 = 8.2, J5a5b = 12.6, H -5); 4.28 (1H, dd, J = 4.2, J5b5a = 12.6, H -5); 6.28
a
5b6
b
(
1H, dd, J = 2.3, J = 4.1, H-2); 6.84 (1H, t, J = 2.3, H-3); 7.03 (1H, dd, J = 2.3, J = 4.1, H-1). Mass spectrum,
21 12
+
+
+
m/z (I , %): 220 [M] (21), 177 [M - CH(CH ) ] (12), 126 [M - C H NO] (100). Found, %: C 70.80; H 9.07; N
rel
3 2
5
3
1
2.69. C H N O. Calculated, %: C 70.90; H 9.09; N 12.72. The reaction of salt 2a with isopropylamine gave
13 20 2
3
c in 20% yield, 1a in 12% yield, and 3a in 3% yield.
1
304

-
1
3
,7,7-Trimethyl-6-methylamino-5,6,7,8-tetrahydroindolizinone (3d). IR spectrum, ν, cm : 3350
1
(
(
NH), 1675 (C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.18, 1.29 (both 2H, both s, 7-(CH ) , 7-(CH ) ); 2.28
3
a
3 b
3H, s, 3-CH ); 2.51 (3H, s, 6-NHCH ); 2.93 (1H, dd, J = 6.8, J65b = 3.8, H-6); 3.80 (1H, dd, J5a5b = 13.1,
3
3
65a
J5a6 = 6.8, H -5); 4.12 (1H, dd, J
= 13.1, J = 3.8, H -5); 6.04 (1H, d, J = 3.7, H-2); 6.95 (1H, d, J = 3.7,
a
5b5a
5b6
b
21
12
+
+
+
H-1). Mass spectrum, m/z (I , %): 206 [M] (42), 121 [M - C(CH ) CHNHCH ] (33), 98 [M - C H NO] (100).
rel
3 2
3
6
5
Found, %: C 69.77; H 8.89; N 13.35. C H N O. Calculated, %: C 69.87; H 8.79; N 13.58.
1
2
18
2
-
1
6
-Ethylamino-3,7,7-trimethyl-5,6,7,8-tetrahydroindolizinone (3e). IR spectrum, ν, cm : 3340 (NH),
1
1
650 (C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.12 (3H, t, J = 7.1, 6-NHCH
s, 7-(CH , 7-(CH ); 2.27 (3H, s, 3-CH ); 2.65, 2.82 (both 1H, both dq, J = 7.1, J = 10.4, 6-NHCH
.03 (1H, dd, J65a = 7.3, J65b = 4.5, H-6); 3.74 (1H, dd, J5a6 = 7.3, J5a5b = 12.5, H -5); 4.11 (1H, dd, J5b6 = 4.5,
5b5a = 12.5, H -5); 6.05 (1H, d, J21 = 3.9, H-2); 6.95 (1H, d, J12 = 3.9, H-1). Mass spectrum, m/z (Irel, %): 220
2
CH
3
); 1.19, 1.29 (both 3H, both
3
)
a
3
)
b
3
a
H
b
CH );
3
3
J
[
a
b
+
+
+
M] (11), 177 [M - CH(CH
Calculated, %: C 70.87; H 9.15; N 12.72.
-Methylamino-5,6,7,8-tetrahydrospiro[cyclopentane-1,7'-indolizinone] (3f). IR spectrum, ν, cm :
3 2 6 5 20 2
) ] (26), [M - C H NO] (100). Found, %: C 70.80; H 9.25; N 12.79. C13H N O.
-
1
6
1
3
2 4
350 (NH), 1660 C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.59 (1H, m, from 7'-(CH ) ); 1.72 (4H, m, from
7
'-(CH ); 1.94 (2H, m, from 7'-(CH ); 2.33 (1H, m, from 7'-(CH ); 2.44 (3H, s, 6-NHCH
2
)
4
2
)
4
2
)
4
3
); 2.95 (1H, t,
J = 3.4, H-6); 4.21 (2H, d, J = 3.4, 5-CH
2
); 6.26 (1H, dd, J = 2.2, J21 = 4.0, H-2); 6.78 (1H, t, J = 2.2, H-3); 6.96
+
+
(
[
1H, dd, J = 2.2, J12 = 4.0, H-1). Mass spectrum, m/z (Irel, %): 218 [M] (36), 162 [M - C
M - C H ] (16), 124 [M - C H NO] (100). Found, %: C 69.88; H 8.50; N 8.50. C13H N O. Calculated, %:
5 9 5 3 18 2
4
H
8
] (20), 149
+
+
C 71.52; H 8.31; N 12.83.
-Ethylamino-5,6,7,8-tetrahydrospiro[cyclopentane-1,7'-indolizinone] (3g). IR spectrum, ν, cm :
-
1
6
1
3
360 (NH), 1660 (C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.06 (3H, t, J = 7.2, 6-NHCH
from 7'-(CH ); 1.89, 1.98, 2.29 (all 1H, all m, from 7'-(CH ); 2.58, 2.78 (both 1H, both dq, J = 7.2, J = 11.3,
-NHCH CH ); 3.16 (1H, t, J = 4.1, H-6); 4.12, 4.20 (both 1H, both dd, J = 4.1, J = 12.9, H -5, H -5); 6.26
1H, dd, J = 2.2, J21 = 4.1, H-2); 6.78 (1H, t, J = 2.2, H-3); 6.96 (1H, dd, J = 2.2, J12 = 4.1, H-1). Mass spectrum,
2 3
CH ); 1.70 (5H, m,
2
)
4
2 4
)
6
(
a
H
b
3
a
b
+
+
5 3 20 2
m/z (Irel, %): 232 [M] (20), 138 [M - C H NO] (100). Found, %: C 72.39; H 8.70; N 11.89. C14H N O.
Calculated, %: C 72.37; H 8.67; N 12.05.
-
1
2
,2-Dimethyl-3-methylamino-α-tetralone (6a). IR spectrum, ν, cm : 3370 (NH), 1680 (C=O).
H NMR spectrum, δ, ppm, (J, Hz): 1.17, 1.28 (both 3H, both s, 2-(CH , 2-(CH ); 2.47 (3H, s, 3-NHCH );
.85 (1H, dd, J34b = 3.7, J34a = 7.2, H-3); 2.90 (1H, dd, J4a3 = 7.2, J4a4b = 16.8, H -4); 3.24 (1H, dd, J4b3 = 3.7,
4b4a = 16.8, H -4); 7.23 (1H, d, J = 7.8, H-6); 7.30 (1H, t, J = 7.8, H-8); 7.46 (1H, dt, J = 7.8, J79 = 1.2, H-7);
1
3
)
a
3
)
b
3
2
a
J
8
1
b
+
+
3 2
.02 (1H, dd, J = 7.8, J97 = 1.2, H-9). Mass spectrum, m/z (Irel, %): 203 [M] (55), 160 ([M - CH(CH ) ] (100),
18 [M - C(CH
+
3
)
2
CHNHCH
3
] (33). Found, %: C 76.64; H 8.53; N 6.83. C13
H17NO. Calculated, %: C 76.81;
H 8.43; N 6.89.
-
1
1
3
-Ethylamino-2,2-dimethyl-α-tetralone (6b). IR spectrum, ν, cm : 3360 (NH), 1670 (C=O). H NMR
spectrum, δ, ppm, (J, Hz): 1.08 (3H, t, J = 7.1, 3-NHCH
2
CH
.59, 2.83 (both 1H, both dq, J = 7.1, J = 11.4, 3-NHCH
.95 (1H, dd, J34b = 2.9, J34a = 7.9, H-3); 3.22 (1H, dd, J4b3 = 2.9, J4b4a = 15.5, H
.30 (1H, t, J = 7.6, H-7); 7.47 (1H, dt, J = 7.6, J68 = 1.5, H-6); 8.02 (1H, dd, J = 7.6, J86 = 1.5, H-8). C NMR
CH ); 19.0 (q, J = 123.1,
); 42.6 (t, J = 129.5, C(4)); 47.0 (s, C(2));
2.0 (d, J = 131.3, C(3)); 126.7 (dd, J = 163.2, J = 8.0, C(5)); 127.8 (dd, J = 161.0, J = 7.6, C(6)); 129.1 (dm,
3
); 1.16, 1.28 (both 3H, both s, 2-(CH
CH ); 2.90 (1H, dd, J4a3 = 7.9, J4a4b = 15.5, H
-4); 7.22 (1H, d, J = 7.6, H-5);
3
)
a
, 2-(CH
3
)
b
);
2
2
7
a
H
b
3
a
-4);
b
1
3
spectrum without proton decoupling, δ, ppm, (J, Hz): 15.4 (q, J = 125.2, 3-NHCH
2
3
2
3 a 3 b 2 3
-(CH ) ); 22.5 (q, J = 127.4, 2-(CH ) ); 31.6 (t, J = 127.8, 3-NHCH CH
6
J = 157.0, C(7)); 131.2 (m, C(4)); 133.3 (dd, J = 159.6, J = 8.8, C(8)); 140.3 (m, C(8a)); 202.4 (s, C(1)). Mass
+
+
spectrum, m/z (Irel, %): 217 [M] (100), 174 [M - CH
2
] (41). Found, %: C 77.45; H 8.42; N 6.52. C14
H19NO.
Calculated, %: C 77.38; H 8.75; N 6.44.
-
1
3
-Methylaminospiro[cyclohexane-1,2'-α-tetralone] (6d). IR spectrum, ν, cm : 3380 (NH), 1680
1
(
C=O). H NMR spectrum, δ, ppm, (J, Hz): 1.55 (7H, m, from 2'-(CH
2
)
5
); 1.75, 1.84, 2.17 (all 1H, all m, from
2
'-(CH ); 2.42 (3H, s, 3-NHCH ); 3.10 (1H, dd, J4a3 = 2.9, J4a4b = 17.3, H
2
)
5
3
a
-4); 3.18 (1H, t, J = 2.9, H-3); 3.25
1
305

(
1H, dd, J = 2.9, J4b4a = 17.3, H
b
-4); 7.23 (1H, d, J = 7.7, H-5); 7.31 (1H, t, J = 7.7, H-7); 7.47 (1H, dt, J68 = 1.4,
+
J = 7.7, H-6); 8.00 (1H, dd, J86 = 1.4, J = 7.7, H-8). Mass spectrum, m/z (I , %): 243 [M] (34), 160
rel
+
+
[M - C H ] (55), 124 [M - C H O] (100). Found, %: C 78.82; H 8.75; N 5.67. C H NO. Calculated, %:
6 11 8 7 16 21
C 78.97; H 8.69; N 5.75.
-
1
3
-Isopropylamino-2,2-dimethyl-α-tetralone (6c). IR spectrum, ν, cm : 3380 (NH), 1680 (C=O).
H NMR spectrum, δ, ppm, (J, Hz): 1.04, 1.06 (both 3H, both d, J = 6.2, 3-NHCH(CH (CH ); 1.17, 1.31
both 3H, both s, 2-(CH ) , 2-(CH ) ); 2.93 (3H, m, 3-NHCH H CH ); 3.12 (1H, dd, J = 3.0, J4a4b = 16.1,
1
3
)
a
3 b
)
(
3
a
3 b
a
b
3
4a3
H -4); 3.18 (1H, dd, J = 3.7, J34a = 3.0, H-3); 3.22 (1H, dd, J4b3 = 3.7, J4b4a = 16.1, H -4); 7.24 (1H, d, J = 7.7,
a
34b
b
H-5); 7.32 (1H, t, J = 7.7, H-7); 7.48 (1H, dt, J = 7.7, J = 1.5, H-6); 8.02 (1H, dd, J = 7.7, J = 1.5, H-8). Mass
6
8
86
+
+
spectrum, m/z (I , %): 231 [M] (68), 188 [M - CH(CH ) ] (25). Found, %: C 77.89; H 9.07; N 6.04.
rel
3 2
C H NO. Calculated, %: C 77.92; H 9.09; N 6.06. The yield of the recyclization product 6c was 25%. The
1
5
21
yield of the dealkylation product 4a was 30%.
REFERENCES
1
2
3
.
.
.
A. N. Kost, S. P. Gromov, and R. S. Sagitullin, Tetrahedron, 37, 3423 (1981).
C. H. van der Plas, Tetrahedron, 41, 237 (1985).
V. I. Terenin, E. V. Kabanova, E. S. Feoktistova, and Yu. G. Bundel', Khim. Geterotsikl. Soedin., 424
(
1989).
A. N. Kost, V. I. Terenin, L. G. Yudin, R. S. Sagitullin, and A. A. Ivkina, Khim. Geterotsikl. Soedin.,
386 (1979).
4
.
1
5
6
.
.
V. I. Terenin, E. V. Kabanova, and Yu. G. Bundel', Khim. Geterotsikl. Soedin., 763 (1991).
W. M. Whaley and T. R. Gvindachari, in: R. Adams, H. Adkins, A. Blate, A. Kopp, F. McGroon,
K. Nieman, and G. Snyder (editors), Organic Reactions [Russian translation], Izd. Inos. Lit., Vol. 6,
Moscow (1953), p. 86.
1
306