Novel nucleophilic rearrangement of 1-substituted isoquinolines using an alcoholic sodium hydroxide solution

Article abstract of DOI:10.1007/s10593-011-0722-3

The reactions of 1-substituted isoquinolinium salts have been studied in the cases of the 1-isopropyl-2-methyl- and 2-methyl-1-cyclohexylisoquinolinium iodides using an alcoholic solution of sodium hydroxide. The possibility of preparing a wide range of spirocyclic ketones, alcohols, amino alcohols, and isochroman-3-ones has been demonstrated.

Full text of DOI:10.1007/s10593-011-0722-3

Chemistry of Heterocyclic Compounds, Vol. 47, No. 1, April, 2011 (Russian Original Vol. 47, No. 1, January, 2011)
NOVEL NUCLEOPHILIC REARRANGEMENT
OF 1-SUBSTITUTED ISOQUINOLINES USING AN
ALCOHOLIC SODIUM HYDROXIDE SOLUTION
V. I. Terenin1*, A. A. Volkov1, A. S. Ivanov1, and E. V. Kabanova1
The reactions of 1-substituted isoquinolinium salts have been studied in the cases of the 1-isopropyl-
2-methyl- and 2-methyl-1-cyclohexylisoquinolinium iodides using an alcoholic solution of sodium
hydroxide. The possibility of preparing a wide range of spirocyclic ketones, alcohols, amino alcohols,
and isochroman-3-ones has been demonstrated.
Keywords: isoquinoline, isochroman-3-one, sodium ethylate, reduction, nucleophilic rearrangement.
It has previously been shown in our laboratory that rearrangement of quaternary isoquinolinium salts
with a methine group at position 1 occurs with an alcoholic alkylamine solution [1]. This recyclization gave a
low yield of -amino--tetralones since the principal route for the reaction is an N-desalkylation to give the
starting isoquinoline. It might be expected that exchange of the N-nucleophile for an O-nucleophile would lead
to a lower yield of side reaction products.
The 1-isopropyl-2-methyl- (1a) and 1-cyclohexyl-2-methyl-isoquinolinium (1b) iodides were prepared
by quaternization of the corresponding isoquinolines by methyl iodide, sealed in an ampoule with an alcoholic
solution of sodium hydroxide, and heated for 18-20 h at 150ºC. Analysis of the reaction mixtures by NMR
spectroscopy showed that the reaction results in a mixture of complex composition. In the initial separation of
the reaction products it was extracted with an acid medium and then with base.
In the case of the 1-isopropyl-2-methylisoquinolinium iodide (1a), extraction of the reaction mixture at
pH below 7 gave the 2,2-dimethyl-1,2-dihydronaphthalin-1-ol (2a) [2-4] and the 1-isopropyl-1,4-dihydro-
(3H)isochroman-3-one (3a) [4]. Extraction from the basic medium gave the 2,2-dimethyl-3-methylamino-
1,2,3,4-tetrahydronaphthalin-1-ol (4a). When a cyclohexyl substituent was present at position 1 of the starting
salt 1b there were obtained the compounds with a spirocyclic structure 2b, 4b and an isochromanone with a
cyclohexyl group at position 1 (compound 3b).
With a shorter heating time (8 h) the amino alcohols 4a,b were not observed and there were separated
from the basic medium the 2,2-dimethyl-3-methylamino-3,4-dihydronaphthalin-1(2H)-one (5a) and the 3'-
(methylamino)-3',4'-dihydro-1'H-spiro(cyclohexane-1,2'-naphthalin)-1'-one (5b), previously reported as the
reaction products of salts 1a,b with an alcoholic methylamine solution [1].
_______
* To whom correspondence should be addressed, e-mail: vter@org.chem.msu.ru.
1M. V. Lomonosov State University, Moscow 119992, GSP-1, Leninskie Gory, 1-3, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 98-106, January, 2011. Original
article submitted January 25, 2010.
74
0009-3122/11/4701-0074©2011 Springer Science+Business Media, Inc.

NHMe
R
O
R
+
+
O
R
R
R
OH
OH
R
4a (17%), b (12%)
3a (21%), b (40%)
2a (35%), b (48%)
EtOH, 20 h, 
NaOH
NHMe
R
NaOH
EtOH, 8 h, 
–
2a (32%), b (28%) + 3a (19%), b (28%)
I
+
N+
R
Me
R
O
R
5a (40%), b (29%)
1a,b
a R = Me, b R+R = (CH2)5
For a comparison of reaction yields the recyclization of salt 1a was carried out at the solvent reflux
temperature. Under these reaction conditions the yield of compounds 2a and 3a falls sharply to ~ 1 and 8%
respectively and in place of amine 4a the tetralone 5a is formed. In addition 1H NMR spectroscopic analysis of
the mixture identified a series of compounds subsequently separated as 2,2-dimethyl-3,4-dihydronaphthalin-
1(2H)-on-3-ol (6a) [5] and 2,2-dimethylnaphthalin-1(2H)-one (7a) [5, 6].
OH
NaOH
EtOH,
3a (8%)
Me
2a (0.7%)
5a (58%)
1a
+
+
Me
Me
+
+

Me
O
O
6a
7a
The mechanism of formation of compounds 3a,b has been described before for 1-phenyl-1,4-dihydro-
3H-isochroman-3-one [7].
Analysis of the structure of the recyclization products using alcoholic sodium hydroxide solution as
compounds 2a,b, 3a,b, and 4a,b led us to conclude that the reaction process involves reduction of the carbonyl
functions to alcohols, evidently via a mechanism similar to a Cannizzaro-Tishchenko reduction. This is
supported by the fact that decreasing the reaction time or temperature gave not the amino alcohols 4a,b but the
aminoketones 5a,b.
The following mechanism is proposed for formation of compounds 2a,b, 4a,b, and 5a,b from the
isoquinolinium salts 1a,b. If formation of alcohols 3a,b can occur as the result of opening of the isoquinoline
ring involving attack of the nucleophile both at position 1 and also at position 3 of the starting salt then the
amino alcohols 4a,b and amino ketones 5a,b can only be formed through attack of hydroxide ion at position 1
and cleavage of the C(1)–N bond.
In order to confirm the relative configuration of amino alcohols 4a,b we carried out a counter synthesis
via reduction of the corresponding amino ketones using alcoholic sodium borohydride. The 1H NMR spectra of
the reaction mixture showed that the material separated is identical to the amino alcohols 4a,b which were
separated from the rearrangement of 1-substituted isoquinolines in the presence of methylamine. Analysis of the
75

B
–
I
N+
R
B
A
A
R
OH
NMe
NHMe
1a,b
O
R
R
R
R
O
NMe
NMe
O
R
H2O
R
R
R
H2O
O
R
R
OH
5a,b
OH
EtONa
EtOH
2a,b
a R = Me, b R+R = (CH2)5
R
EtONa
EtOH
R
4a,b
O
1H NMR spectra of the amino alcohols 4a,b showed doubling of the number of signals for the reduced ring and
substituent pointing to the presence of diastereomer pairs due to the difference (cis and trans) in orientation of
the aminomethyl and hydroxyl groups.
NHMe
NHMe
NaBH4
EtOH
5a,b
+
R
R
R
R
OH
4'a,b
OH
4"a,b
In order to confirm our proposal that alcoholic sodium ethylate solution reduced the carbonyl group
formed during the reaction, a change was made from the alcoholic solution of base to an aqueous solution of the
same concentration. In this case the reaction mixture was extracted with benzene without acid treatment. After
distillation of the solvent, the organic extract was either hydrolyzed with acid solution (method A) or reduced
with alcoholic sodium borohydride (method B). In both case subsequent extraction was carried out in two
stages, initially from acid and then from basic solutions (as in the case of the alcoholic solution of base).
Treatment of the 1-isopropyl-2-methylisoquinolinium iodide (1a) with acid (method A) gave
compounds 5a, 6a [5], 7a [5, 6], and 2-methylisoquinolin-1(2H)-one (8) [8]. Under the same conditions the salt
1b gave compounds 5b, 6b, 7b and 8 (for Scheme see page 77).
76

1) NaOH, H2O, 
2) NaBH4, EtOH
1) NaOH, H2O, 
2) NaBH4, EtOH
OH
R
OH
1b
2a
4a
+
1a
+
8
8 +
4b +
+
R
O
OH
6b
9b
6 b R + R = (CH2)5
B
N
–
I
N+
R
O
8
A
R
1a,b
H
OH
OH
N
R
N
OH
R
R
R
NHMe
O
R
NMe
R
R
R
NMe
O
O
H
O
R
NMe
R
O
R
R
R
R
O
O
NMe
R
R
R
R
R
R
NHMe
OH
OH
6a,b
5a,b
OH
R
R
NMe
R
R
O
7a,b
a R = Me, b R+R = (CH2)5
77

The reduction of the reaction mixture (method B) from salt 1a gave compounds 2a, 4a, 8. Salt 1b gave the
amino alcohol 4b, 1'H-spiro(cyclohexane-1,2'-naphthalin)-1'-on-3'-ol (6b), 1'H-spiro(cyclohexane-1,2'-napthaline)-
1',3'-diol (9b), and 2-methylisoquinolin-1(2H)-one (8).
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Bruker Avance-400 spectrometer (400 and 100 MHz
respectively) using CDCl3 at 23ºC with TMS as internal standard. Mass spectra were taken on a Kratos MS-90
instrument with ionization energy 70 eV. High resolution spectra were recorded on a Bruker microTOF II
instrument using electrospray ionization (ESI) [9]. Measurement were carried out for positive ions (capillary
voltage -4500 V) or negative ions (capillary voltage 3200 V). The mass scanning range was m/z 50-3000 D with
external or internal calibration (Electrospray Calibrant Solution, Fluka). Spray introduction was used for
solutions in acetonitrile, methanol, or water with a flow rate of 3 l/min. The gas carrier (4 l/min) was nitrogen
and the interface temperature 180ºC. Monitoring of the reaction course and purity of the compounds was carried
out by TLC on Silufol-254 plates (254 nm) or Alufol in the systems benzene or benzene–ethyl acetate (1:1).
Reaction of 1-Substituted Isoquinolinium Salts with Alcoholic Sodium Hydroxide Solution
(General Method). A mixture of the isoquinolinium salt (1a,b) (1 mmol) and a 10% alcoholic solution of
sodium hydroxide (4-5 ml) was heated from 8 to 20 h, cooled to room temperature, and the solvent was
evaporated. The residue was dissolved in water, HCl solution added to pH ˂ 7, extracted with benzene, the
organic phase dried over CaCl2, and the solvent evaporated in vacuo. The reaction products were separated by
column chromatography on SiO2 (35-60 nm) eluting with benzene and subsequently increasing the polarity to
benzene–ethyl acetate (1:1). The mother liquor was neutralized with sodium carbonate, extracted with benzene,
the organic phase dried over CaCl2, and the solvent was evaporated in vacuo to give the amines.
When heated in a sealed ampoule at 150ºC for 18-20 h the 1-isopropyl-2-methylisoquinolinium iodide
(1a) (0.313 g, 1 mmol) gave compound 2a (0.062 g, 35%), compound 3a (0.040 g, 21%), compound 4a as an
diastereomeric pair (0.033 g, 17%). When heated for 8 h it gave compound 2a (0.055 g, 32%), compound 3a
(0.036 g, 19%), and compound 5a (0.080 g, 40%). When refluxed for 14 h it gave compound 2a (0.002 g, 1%);
compound 3a (0.015 g, 8%), compound 5a (0.118 g, 58%), and the compounds 6a and 7a in trace amounts.
When heated in a sealed ampoule at 150ºC for 18-20 h the 1-cyclohexyl-2-methylisoquinolinium iodide
(1b) (0.345 g, 1 mmol) gave compound 2b (0.103 g, 48%), compound 3b (0.092 g, 40%), and compound 4b (as
a mixture of two diastereomers, 0.03 g, 12%). When heated for 8 h it gave compound 2b (0.060 g, 28%) and
compound 3b (0.092 g, 40%). Upon refluxing for 8 h it produced compound 2b (0.060 g, 28%), compound 3b
(0.065 g, 28%), and compound 5b (0.070 g, 25%).
Reaction of 1-Substituted Isoquinolinium Salts with Aqueous Sodium Hydroxide Solution. A. A
mixture of the isoquinolinium iodide 1a,b (1 mmol) and 10% aqueous sodium hydroxide solution (4-5 ml) was
heated in a sealed ampoule for 9 h at 150ºC, cooled to room temperature, water (20 ml) added, and extracted
with benzene. The organic phase was dried over CaCl2 and solvent was evaporated in vacuo. The residue was
treated with 5% aqueous hydrochloric acid (20 ml), stirred for 30 min at room temperature, and extracted with
benzene. The organic phase was dried over CaCl2 and the solvent was evaporated in vacuo. The reaction
products were separated by column chromatography on SiO2 (35-60 nm) eluting with benzene and subsequently
increasing the polarity to benzene–ethyl acetate (1:1). The mother liquor was basified with sodium carbonate,
extracted with benzene, the organic phase dried over CaCl2, and the solvent was evaporated in vacuo to give the
amines.
The 1-isopropyl-2-methylquinolinium iodide (1a) (0.313 g, 1 mmol) gave compound 6a (0.009 g,
4.7%), compound 7a (0.034 g, 20%), compound 8 (0.009 g, 6%), and compound 5a (0.013 g, 6%).
The 1-cyclohexyl-2-methylisoquinolinium iodide (1b (0.345 g, 1 mmol) gave: compound 6b (0.035 g,
15%), compound 7b (0.010 g, 5%), compound 8 (0.016 g, 10%), and compound 5b (0.030 g, 12%).
78

B. A mixture of the isoquinolinium iodide 1a,b (1 mmol) and 10% aqueous sodium hydroxide solution
(4-5 ml) was heated for 9 h in an ampoule at 150ºC, cooled to room temperature, water (20 ml) added, and
extracted with benzene. The organic phase was dried over CaCl2 and solvent was evaporated in vacuo. The
residue was dissolved in alcohol, sodium borohydride was added, and stirred for 1 h. The residual sodium
borohydride was neutralized using conc. HCl solution and solvent was evaporated in vacuo. Water (20 ml) was
added to the residue followed by HCl solution to pH ˂ 7, and extracted with benzene. The organic phase was
dried over CaCl2 and solvent was evaporated in vacuo. The reaction products were separated by column
chromatography on SiO2 (35-60 nm) eluting with benzene and subsequently increasing the polarity to benzene–
ethyl acetate (1:1). The mother liquor was basified with sodium carbonate, extracted with benzene, the organic
phase dried over CaCl2, and the solvent was evaporated in vacuo to give the amines.
The 1-isopropyl-2-methylisoquinolinium iodide (1a) (0.313 g, 1 mmol) gave compound 2a (0.015 g,
9%), compound 8 (0.026 g, 16%), and compound 4a (as one diastereomer, 0.049 g, 24%).
The 1-cyclohexyl-2-methylisoquinolinium iodide (1b) (0.345 g, 1 mmol) gave compound 2b (0.010 g,
4%), compound 9b (0.012 g, 5%), compound 8 (0.012 g, 8%), and compound 4b (0.054 g, 22%).
1
2,2-Dimethyl-1,2-dihydronaphthalin-1-ol (2a). H NMR spectrum, , ppm (J, Hz): 1.09 (3H, s, CH3);
1.14 (3H, s, CH3); 1.74 (1H, br. s, OH); 4.41 (1H, s, H-1); 5.78 (1H, d, J3,4 = 9.6, H-3); 6.40 (1H, d, J4,3 = 9.5,
H-4); 7.11-7.09 (1H, m, H-5); 7.28-7.25 (2H, m, H-6,7); 7.43-7.40 (1H, m, H-8). 13C NMR spectrum, , ppm:
21.18 (CH3); 25.62 (CH3); 37.41 (C-2); 77.11 (C-1); 124.88 (C-8); 126.17 (C-5); 126.91 (C-7); 127.63 (C-6);
128.04 (C-4); 131.95 (C-4a); 136.62 (C-8a); 138.15 (C-3). Mass spectrum, m/z (Irel, %): 174 [M]+ (28.05), 159
(45.88), 141 (22.77), 131 (100.00), 128 (31.25), 118 (75.83), 115 (46.40), 103 (13.65), 91 (28.82).
1
1'H-Spiro(cyclohexane-1,2'-naphthalin)-1'-ol (2b). H NMR spectrum, , ppm (J, Hz): 1.71-1.28
(10H, m, C5H10), 1.80 (1H, br. s, OH); 4.37 (1H, s, H-1); 6.05 (1H, d, J3,4 = 9.7, H-3); 6.49 (1H, d, J4,3 = 9.8, H-
4); 7.13-7.11 (1H, m, H-5); 7.31-7.23 (2H, m, H-6,7) ; 7.36-7.34 (2H, m, H-8). 13C NMR spectrum, , ppm:
21.52, 22.35, 26.11, 30.37, 33.62 (C5H10); 39.96 (C-2); 76.12 (C-1); 125.22 (C-8); 126.31 (C-5); 127.63 (C-7);
128.00 (C-6); 128.32 (C-4); 132.11 (C-8a); 135.57 (C-3); 136.33 (C-4a). Mass spectrum, m/z (Irel, %): 214 [M]+
(10.14), 196 (5.93), 171 (10.23), 159 (28.43), 141 (26.69), 131 (69.10), 115 (69.92), 99 (46.07), 77 (49.09).
Found, %: С 84.01; Н 8.45. C15H18O. Calculated, %: С 84.07; Н 8.47.
1
1-Isopropyl-1,4-dihydro(3H)isochroman-3-one (3a). H NMR spectrum, , ppm (J, Hz): 1.08 (6H, d,
J = 6.7 CHCH3); 2.23 (1H, quin, J = 6.7, CHCH3); 3.70 (1H, d, J4',4'' = 19.3, H-4'); 3.80 (1H, d, J4'',4' = 19.3,
H-4''); 5.11 (1H, d, J1,9 = 6.36, H-1); 7.21-7.19 (2H, m, H-5,8); 7.34-7.31 (2H, m, H-6,7). 13C NMR spectrum, ,
ppm: 17.32 (1-CH3); 19.47 (2-CH3); 33.15 (CHCH3); 35.38 (C-5); 86.71 (C-1); 125.60 (C-7); 126.93 (C-5);
127.51 (C-6); 128.30 (C-8); 130.22 (C-4a); 133.27 (C-8a); 170.48 (C-3). Mass spectrum, m/z (Irel, %): 190 [M]+
(47.45), 170 (11.56), 149 (56.53), 147 (80.31), 146 (35.58), 121 (51.64), 119 (100.00), 91 (67.82), 89 (17.49).
1
1-Cyclohexyl-1,4-dihydro(3H)isochroman-3-one (3b). H NMR spectrum, , ppm (J, Hz): 1.96-1.17
(11H, m, C6H11); 3.70 (1H, d, J4',4'' = 19.4, H-4'); 3.80 (1H, d, J4'',4' = 19.4, H-4''); 5.13 (1H, d, J1,9 = 6.9, H-1);
7.20-7.16 (2H, m, H-5,8); 7.34-7.31 (2H, m, H-6,7). 13C NMR spectrum, , ppm: 25.74, 25.95 (2C), 27.88,
29.57, 42.90 (C6H11); 35.35 (C-4); 86.38 (C-1); 125.79 (C-7); 126.80 (C-5); 127.52 (C-6); 128.23 (C-8); 130.10
(C-4a); 133.04 (C-8a); 170.53 (C-3). Mass spectrum, m/z (Irel, %): 230 [M]+ (2.70), 149 (15.06), 148 (61.52),
147 (61.20), 146 (11.03), 128 (8.64), 119 (87.97), 105 (33.16), 91 (92.46), 77 (15.16). Found: 231.1386 [M+1].
C15H18O2. Calculated: 231.1380.
2,2-Dimethyl-3-methylamino-1,2,3,4-tetrahydronaphthalin-1-ol (4a) (as an approximately 3:1
1
mixture of diastereomers). H NMR spectrum, , ppm (J, Hz): 0.99 (0.93) (3H, s, CH3); 1.28 (1.24) (3H, s,
CH3); 2.45 (2.59) (3H, s, NHCH3); 2.77 (1H, dd, J3,4' = 4.9, J3,4'' = 3.6, H-3); 2.92 (1H, dd, J4',3 = 3.7, J4',4'' = 17.6,
H-4'); 3.09 (1H, dd, J4'',3 = 5.0, J4'',4' = 17.6, H-4''); 4.17 (4.33) (1H, s, H-1); 7.47-7.11 (1H, m, H-5); 7.26-7.21
(2H, m, H-6,7); 7.45-7.42 (1H, m, H-8). Mass spectrum, m/z (Irel, %): 205 [M]+ (7.05), 174 (2.67), 159 (3.77),
144 (12.109), 131 (9.03), 119 (9.52), 91 (12.29), 85 (15.49). Found, %: С 75.89; Н 9.31; N 6.72. C13H19NO.
Calculated, %: С 76.06; Н 9.33; N 6.82.
79

3'-(Methylamino)-3',4'-dihydro-1'H-spiro(cyclohexane-1,2'-naphthalin)-1'-ol (4b) (as an approximately
3:1 mixture of diastereomers). 1H NMR spectrum, , ppm (J, Hz): 1.73-1.30 (10H, m, C5H10); 2.55 (2.42) (3H, s,
NHCH3); 2.69 (1H, dd, J4',3 = 8.0, J4',4'' = 16.8, H-4'); 3.04 (1H, dd, J3,4' = 8.1, J3,4'' = 5.3, H-3); 3.15 (1H, dd, J4'',3
= 5.2, J4'',4' = 16.8, H-4''); 4.84 (4.41) (1H, s, H-1); 7.16-7.11 (1H, m, H-5); 7.25-7.22 (2H, m, H-6,7); 7.45-7.39
(1H, m, H-8). Mass spectrum, m/z (Irel, %): 245 [M]+ (2.65), 214 (9.78), 162 (1.39), 144 (7.57), 120 (7.44), 119
(12.31), 91 (30.81), 83 (19.27), 77 (14.10). Found: 246.1859 [M+1]. C16H23NO. Calculated: 246.1852.
1
2,2-Dimethyl-3-methylamino-3,4-dihydronaphthalin-1(2H)-one (5a). H NMR spectrum, , ppm (J,
Hz): 1.20 (3H, s, CH3); 1.31 (3H, s, CH3); 2.49 (1H, s, NHCH3); 2.88 (1H, dd, J3,4' = 3.7, J3,4'' = 7.2, H-3); 2.95
(1H, dd, J4',3 = 3.7, J4',4'' = 16.7, H-4'); 3.27 (1H, dd, J4'',3 = 7.2, J4'',4' = 16.7, H-4''); 7.25 (1H, d, J5,6 = 7.6, H-5);
7.31 (1H, dd, J7,6 = 7.3, H7,8 = 7.8, H-7); 7.50 (1H, dd, J6,7 = 7.4, J6,5 = 7.6, H-6); 8.04 (1H, d, J8,7 = 7.7, H-8).
3'-(Methylamino)-3',4'-dihydro-1'H-spiro(cyclohexane-1,2'-naphthalin)-1'-one (5b). 1H NMR
spectrum, , ppm (J, Hz): 2.16-1.46 (10H, m, H-10 to H-14); 2.40 (1H, s, H-9); 3.07 (1H, dd, J4',3 = 2.8,
J4',4'' = 17.4, H-4'); 3.16 (1H, dd, J3.4' = 2.9, J3,4'' = 3.3, H-3); 3.24 (1H, dd, J4'',3 = 3.4, H4'',4' = 17.4, H-4''); 7.22
(1H, d, J5,6 = 7.7, H-5); 7.29 (1H, dd, J7,6 = 7.3, J7,8 = 7.8, H-7); 7.46 (1H, dd, J6,7 = 7.4, J6,5 = 7.6, H-6); 7.99
(1H, d, J8,7 = 7.8, H-8).
1
2,2-Dimethyl-3,4-dihydronaphthalin-1(2H)-on-3-ol (6a). H NMR spectrum, , ppm (J, Hz): 1.25
(3H, s, CH3); 1.29 (3H, s, CH3); 3.10 (1H, dd, J4',3 = 7.1, J4',4'' = 17.0, H-4'); 3.32 (1H, dd, J4'',3 = 4.0, J4'',4´ = 17.1,
H-4''); 4.08 (1H, dd, J3,4' = 7.1, J3,4'' = 4.0, H-3); 7.28 (1H, d, J5,6 = 7.4, H-5); 7.35 (1H, dd, J7,8 = 7.7, J7,6 = 7.5,
H-7); 7.52 (1H, dd, J6,7 = 7.5, J6,5 = 7.5, H-6); 8.06 (1H, d, J = 7.8, H-8). 13C NMR spectrum, , ppm: 18.73
(CH3); 21.99 (CH3); 34.20 (C-4); 47.86 (C-2); 74.71 (C-3); 127.04 (C-7); 127.84 (C-5); 129.33 (C-8); 130.91
(C-8a); 133.65 (C-6); 138.94 (C-4a); 201.68 (C-1). Mass spectrum, m/z (Irel, %): 190 [M]+ (60.75), 172 (81.17),
157 (63.30), 147 (98.03), 134 (100.00), 129 (63.40), 118 (70.67), 105 (8.35), 90 (75.05).
1'H-Spiro(cyclohexane-1,2'-naphthalin)-1'-on-3'-ol (6b). 1H NMR spectrum, , ppm (J, Hz):
2.21-1.43 (10H, m, C5H10); 3.08 (1H, dd, J4',3 = 3.7, J4',4'' = 17.7, H-4'); 3.42 (1H, dd, J4'',3 = 3.4, J4'',4' = 17.6,
H-4''); 4.32 (1H, dd, J3,4' = 3.5, J3,4'' = 3.5, H-3); 7.24 (1H, d, J5,6 = 7.6, H-5); 7.34 (1H, dd, J7,8 = 7.6, J7,6 = 7.5,
H-7); 7.51 (1H, dd, J6,7 = 7.5, J6,5 = 7.6, H-6); 8.02 (1H, d, J = 7.7, H-8). 13C NMR spectrum, , ppm: 21.60,
22.34, 25.75, 28.07, 31.40 (C5H10); 33.35 (C-4); 50.32 (C-2); 73.14 (C-3); 126.83 (C-7); 127.41 (C-5); 129.36
(C-8); 131.75 (C-8a); 133.39 (C-6); 138.14 (C-4a); 202.27 (C-1). Mass spectrum, m/z (Irel, %): 230 [M]+ (20.33),
212 (6.10), 186 (7.04), 175 (34.43), 161 (35.07), 147 (19.10), 115 (24.47), 95 (100.00), 91 (85.60). Found, %:
С 78.29; Н 7.94. C15H18O2. Calculated, %: С 78.23; Н 7.88.
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2,2-Dimethylnaphthalin-1(2H)-one (7a). H NMR spectrum, , ppm (J, Hz): 1.28 (6H, s, 2CH3); 6.10
(1H, d, J3,4 = 9.7, H-3); 6.50 (1H, d, J4,3 = 9.7, H-4); 7.22 (1H, d, J5,6 = 7.6, H-5); 7.36 (1H, dd, J7,8 = 7.7,
J
7,6 = 7.5, H-7); 7.57 (1H, dd, J6,7 = 7.5, J6,5 = 7.6, H-6); 8.06 (1H, d, J8,7 = 7.8, H-8). 13C NMR spectrum, ,
ppm: 25.88 (2CH3); 45.23 (C-2); 122.53 (C-6); 127.15 (C-4,8); 127.75 (C-7); 128.82 (C-8a); 134.28 (C-5);
138.39 (C-4a); 141.26 (C-3); 203.68 (C-1). Mass spectrum, m/z (Irel, %): 172 [M]+ (78.84), 157 (51.96), 143
(13.49), 129 (100.00), 128 (76.60), 127 (30.23), 115 (25.09), 102 (18.80), 89 (12.24).
1
1'H-Spiro(cyclohexane-1,2'-naphthalin)-1'-one (7b). H NMR spectrum, , ppm (J, Hz): 1.95-1.45
(10H, m, C5H10); 6.61 (2H, s, H-3,4); 7.25 (1H, d, J5,6 = 7.5, H-5); 7.36 (1H, dd, J7,8 = 7.7, J7,6 = 7.5, H-7); 7.57
(1H, dd, J6,7 = 7.5, J6,5 = 7.6, H-6); 8.06 (1H, d, J8,7 = 7.9, H-8). 13C NMR spectrum, , ppm: 21.45 (2C), 25.56,
34.18 (2C), (C5H10); 48.86 (C-2); 123.30 (C-4); 126.99 (C-5); 127.14 (C-8); 127.73 (C-7); 129.20 (C-8a);
134.14 (C-6); 135.82 (C-4a); 137.50 (C-3); 204.02 (C-1). Mass spectrum, m/z (Irel, %): 212 [M]+ (61.55), 183
(21.20), 170 (20.04), 157 (100.00), 141 (54.16), 128 (96.11), 115 (80.16), 102 (37.59), 77 (44.37). Found, %:
С 85.04; Н 7.58. C15H18O. Calculated, %: С 84.87; Н 7.60.
2-Methylisoquinolin-1(2H)-one (8). 1H NMR spectrum, , ppm (J, Hz): 3.62 (3H, s, CH3); 6.51 (1H, d,
J3,4 = 7.2, H-3); 7.09 (1H, d, J4,3 = 7.3, H-4); 7.54-7.49 (2H, m, H-5,6); 7.67 (1H, dd, J7,8 = 8.0, J7,6 = 6.9, H-7);
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8.46 (1H, d, J8,7 = 8.0, H-8). Mass spectrum, m/z (Irel, %): 159 [M]+ (100.00), 130 (32.35), 118 (24.97), 116
(39.36), 103 (11.68), 90 (28.21), 89 (56.65), 77 (23.74), 63 (41.05).
1
1'-H-Spiro(cyclohexane-1,2'-naphthaline)-1',3'-diol (9b). H NMR spectrum, , ppm (J, Hz): 1.67-
1.30 (10H, m, C6H10); 2.82 (1H, dd, J4',3 = 8.1, J4',4'' = 17.2, H-4'); 3.15 (1H, d, J4'',3 = 5.6, J4'',4' = 17.3, H-4''); 4.31
(1H, dd, J3,4'' = 5.7, J3,4' = 8.1, H-3); 4.88 (1H, s, H-1); 7.14-7.11 (1H, m, H-5); 7.25-7.21 (1H, m, H-6,7); 7.44-
7.42 (1H, m, H-8). 13C NMR spectrum, , ppm: 21.23, 21.32, 25.53, 26.24, 27.63 (C5H10); 34.15 (C-4); 40.63
(C-2); 68.65 (C-1); 71.77 (C-3); 126.66 (C-6); 127.83 (C-7); 129.05 (C-5); 129.24 (C-8); 134.07 (C-4a); 137.28
(C-8a). Mass spectrum, m/z (Irel, %): 214 [M–18]+ (60.45), 185 (2.20), 171 (18.58), 158 (17.01), 132 (24.85),
120 (100.00), 119 (72.65), 104 (19.41), 91 (72.30), 77 (40.07). Found: 233.1544 [M+1]. C15H20O2. Calculated:
233.1538.
Measurements of high resolution mass spectra were made in the Structural Investigation Department of
the Institute of Organic Chemistry, Russian Academy of Sciences, Moscow.
REFERENCES
1.
V. I. Terenin and A. S. Ivanov, Khim. Geterotsikl. Soedin., 296 (2005). [Chem. Heterocycl. Comp., 41,
265 (2005)].
2.
3.
4.
5.
D. Armesto, M. J. Ortiz, A. R. Agarrabeitia, and M. Martin-Fontecha, Org. Lett., 6, 2261 (2004).
J. Shabtai, H. Klemm, and D. R. Taylor, J. Org. Chem., 3, 1489 (1968).
B. Wuench, Arch. Pharm., 323, 493 (1990).
M. P. Coogan, R. Haigh, A. Hall, L. D. Harris, D. E. Hibbs, R. L. Jenkins, C. L. Jones, and
N. C. O. Tomkinson, Tetrahedron, 59, 7389 (2003).
6.
7.
C. Almansa, L. A. Gomez, F. L. Cavalcanti, R. Rodriguez, E. Carceller, J. Bartroli, J. Garcia-Rafanell,
and J. Forn, J. Med. Chem., 36, 2121 (1993).
V. I. Terenin, A. A. Volkov, A. S. Ivanov, and E. V. Kabanova, Khim. Geterotsikl. Soedin., 454 (2010).
[Chem. Heterocycl. Comp., 45, 361 (2010)].
8.
9.
A. P. Venkov and S. M. Statkova-Abeghe, Tetrahedron, 52, 1451 (1996).
P. A. Belyakov, V. I. Kadentsev, A. O. Chizhov, N. G. Kolotyrkina, A. S. Shashkov, and
V. P. Ananikov, Mendeleev Commun., 20, 125 (2010).
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