Synthesis and some transformations of 4-aryl-substituted amines of the tetrahydropyran series

Article abstract of DOI:10.1134/S1070428011010143

The reaction of 2-isopropyltetrahydropyran-4-one [obtained by isomerization and hydration of 3-isopropylpent-1-en-4-yn-3-ol in the presence of 5% sulfuric acid and mercury(II) sulfate] with ethyl cyanoacetate gave ethyl cyano(2-isopropyltetrahydropyran-4-

Full text of DOI:10.1134/S1070428011010143

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 1, pp. 115–119. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © N.S. Arutyunyan, L.A. Akopyan, N.Z. Akopyan, G.A. Panosyan, G.A. Gevorgyan, 2011, published in Zhurnal Organicheskoi Khimii,
2011, Vol. 47, No. 1, pp. 116–120.
Synthesis and Some Transformations of 4-Aryl-Substituted
Amines of the Tetrahydropyran Series
N. S. Arutyunyana, L. A. Akopyana, N. Z. Akopyana, G. A. Panosyanb, and G. A. Gevorgyana
a Mndzhoyan Institute of Fine Organic Chemistry, Research and Technology Center of Organic
and Pharmaceutical Chemistry, National Academy of Sciences of Armenia,
pr. Azatutyan 26, Erevan, 0014 Armenia
e-mail: gyulgev@gmail.com
b Molecular Structure Research Center, National Academy of Sciences of Armenia, Erevan, Armenia
Received December 7, 2009
Abstract—The reaction of 2-isopropyltetrahydropyran-4-one [obtained by isomerization and hydration of
3-isopropylpent-1-en-4-yn-3-ol in the presence of 5% sulfuric acid and mercury(II) sulfate] with ethyl cyano-
acetate gave ethyl cyano(2-isopropyltetrahydropyran-4-ylidene)acetate which was treated with 4-tolylmagne-
sium chloride. The resulting ethyl cyano[2-isopropyl-4-(4-tolyl)tetrahydropyran-4-yl]acetate was subjected to
decarbethoxylation to obtain 2-isopropyl-4-(4-tolyl)tetrahydropyran-4-ylacetonitrile. The latter was reduced to
the corresponding amine with lithium tetrahydridoaluminate, and the reduction product was brought into con-
densation with aromatic aldehydes. The Schiff bases thus formed were reduced with sodium tetrahydridoborate,
followed by N-acylation with acetyl and propionyl chlorides.
DOI: 10.1134/S1070428011010143
We previously reported on the synthesis and trans-
formations of 2-[2-isopropyl-4-(o-methoxyphenyl)-
tetrahydropyran-4-yl]ethanamine [1]. With a view to
find a relation between the structure of compounds and
their biological activity (antibacterial, anti-inflam-
matory, anesthetic) in the present work we synthesized
analogous derivatives having a 4-methylphenyl substit-
uent. By reaction of 2-isopropyltetrahydropyran-4-one
(I) with ethyl cyanoacetate we obtained tetrahydro-
pyranylidene-substituted ethyl cyanoacetate II which
reacted with 4-tolylmagnesium chloride to produce
ester III. Treatment of III with potassium hydroxide
resulted in elimination of the ester group with forma-
tion of nitrile IV. The latter was reduced to primary
amine V with lithium tetrahydridoaluminate, and con-
densation of V with a series of aromatic aldehydes
afforded Schiff bases VI which were reduced (without
isolation from the reaction mixture) to the correspond-
ing secondary amines VII–XI with NaBH4. Acylation
of amines VII–XI with acetyl and propionyl chlorides
gave amides XII–XXI (Scheme 1).
EXPERIMENTAL
The IR spectra were measured on a Specord 75IR
1
spectrometer. The H and 13C NMR spectra were
recorded on a Varian Mercury VX-300 instrument at
300.08 and 75.46 MHz, respectively, using DMSO-d6–
CCl4 (1:3) as solvent and tetramethylsilane as internal
reference.
2-Isopropyltetrahydropyran-4-one (I). A mixture
of 400 ml of 20% sulfuric acid, 400 g (3.2 mol) of
3-isopropylpent-1-en-4-yn-3-ol, and 15 g of HgSO4 in
1.1 l of acetone was heated for 20 h at 62°C under
vigorous stirring. During this time, additional 30 g of
HgSO4 was added in portions. The most part of the
solvent was distilled off, and the residue was saturated
with potassium carbonate and extracted with diethyl
ether. The extract was dried over Na2SO4 and evap-
orated, and the residue was distilled under reduced
pressure. Yield 338.3 g (74%), bp 67–69°C (4 mm).
1H NMR spectrum, δ, ppm: 0.92 d (3H, CH3, J =
6.8 Hz), 0.95 d (3H, CH3, J = 6.8 Hz), 1.75 sept.d [1H,
CH(CH3)2, J = 6.8, 5.9 Hz], 2.18 m (1H, 3-H), 2.22–
2.25 m (2H, 3-H, 5-H), 2.51 m (1H, 5-H), 3.26 m (1H,
2-H), 3.57 d.d.d (1H, 6-H, J = 12.4, 11.3, 2.8 Hz),
The structure of the newly synthesized compounds
1
was confirmed by their elemental analyses and H and
13C NMR spectra.
115

ARUTYUNYAN et al.
116
Scheme 1.
O
Me
O
O
O
4-MeC6H4MgCl
N
Me
CN
Me
+
Me
OEt
CN
O
Me
Me
O
O
OEt
Me
OEt
III
I
II
Me
Me
Me
O
O
O
LiAlH4
KOH
RCHO
Me
Me
Me
R
Me
Me
Me
NC
IV
NH2
N
V
VI
Me
Me
O
O
NaBH4
R'COCl
Me
Me
R
R'
Me
Me
HN
N
R
O
VII–XI
XII–XXI
VII, R = Ph; VIII, R = 4-MeOC6H4; IX, R = 3,4-(MeO)2C6H3; X, R = 2-FC6H4; XI, R = 2-furyl; XII, R = Ph, R′ = Me; XIII, R = Ph,
R′ = Et; XIV, R = 4-MeOC6H4, R′ = Me; XV, R = 4-MeOC6H4, R′ = Et; XVI, R = 4-i-PrOC6H4, R′ = Me; XVII, R = 4-i-PrOC6H4,
R′ = Et; XVIII, R = 2-FC6H4, R′ = Me; XIX, R = 2-FC6H4, R′ = Et; XX, R = 2-furyl, R′ = Me; XXI, R = 2-furyl, R′ = Et.
4.22 d.d.d (1H, 6-H, J = 11.3, 7.4, 1.4 Hz). 13C NMR
spectrum, δC, ppm: 17.46 and 17.55 (CH3), 32.45
(CHCH3), 41.53 (C3), 44.63 (C5), 65.67 (C6), 81.83
(C2), 204.71 (CO). Found, %: C 67.55; H 9.93.
C8H14O2. Calculated, %: C 67.57; H 9.92.
N 5.87. C13H19NO3. Calculated, %: C 65.80; H 8.07;
N 5.90.
[2-Isopropyl-4-(4-tolyl)tetrahydropyran-4-yl]-
acetonitrile (IV) was synthesized according to the
procedure described in [2]. Yield 93%, bp 164–166°C
(2 mm). IR spectrum: ν 2230 cm–1 (CN). Found, %:
C 79.36; H 8.99; N 5.41. C17H23NO. Calculated, %:
C 79.33; H 9.01; N 5.44.
Ethyl cyano(2-isopropyltetrahydropyran-4-yli-
dene)acetate (II) was synthesized according to the
procedure described in [2]. The product was a mixture
of E and Z isomers at a ratio of 1 : 1. Yield 74%,
bp 120–124°C (2 mm). IR spectrum, ν, cm–1: 2225
(CN), 1720 (C=O), 1610 (C=C). 1H NMR spectrum, δ,
ppm: 0.97 d (1.5H, J = 6.8 Hz), 0.96 d (1.5H, J =
6.8 Hz), 0.97 d (1.5H, J = 6.8 Hz), 0.98 d (1.5H, J =
6.8 Hz) [CH(CH3)2], 1.36 t (1.5H, CH3CH2O, J =
7.1 Hz), 1.36 t (1.5H, CH3CH2O, J = 7.1 Hz), 1.79 m
[1H, CH(CH3)2], 2.04 d.d (0.5H, J = 13.8, 10.7 Hz)
and 2.29 d.d (0.5H, J = 13.5, 10.7 Hz) (3-H),
2.34 d.d.d (0.5H, J = 14.3, 11.7, 6.3 Hz) and 2.56 d.d.d
(0.5H, J = 14.0, 11.7, 6.3 Hz) (3-H), 2.87 m (1H),
3.06 d.d.d (0.5H, J = 10.7, 5.8, 2.1 Hz) and 3.16 d.d.d
(0.5H, J = 10.7, 5.8, 2.1 Hz) (2-H), 3.38 t.d (0.5H,
J = 11.4, 2.5 Hz), 3.48 t.d (0.5H, J = 11.4, 2.5 Hz),
3.84 d.q (0.5H, J = 14.3, 1.6 Hz), 3.92 d.t (0.5H, J =
13.8, 2.1 Hz), 4.15 d.d.d (0.5H, J = 11.2, 6.3, 1.8 Hz),
4.22 d.d.d (0.5H, J = 11.2, 6.3, 1.8 Hz), 4.26 q (2H,
OCH2CH3, J = 7.1 Hz). Found, %: C 65.85; H 8.00;
2-[2-Isopropyl-4-(4-tolyl)tetrahydropyran-4-yl]-
ethanamine (V). A solution of 12.2 g (0.32 mol) of
LiAlH4 in 200 ml of anhydrous diethyl ether was
cooled to 0–2°C, a solution of 42 g (0.16 mol) of
nitrile IV in diethyl ether was added dropwise, the
mixture was stirred for 1 h at that temperature and
cooled to –10°C (NaCl–ice bath), and 12 ml of water,
12 ml of a 15% solution of sodium hydroxide, and
36 ml of water were added in succession. The mixture
was filtered, the inorganic precipitate was washed with
diethyl ether, the organic phase of the filtrate was com-
bined with the washings, dried, and evaporated, and
the residue was distilled under reduced pressure. Yield
41 g (94%), bp 155–157°C (1.5 mm). IR spectrum:
ν 3300 cm–1 (NH2). 1H NMR spectrum, δ, ppm: 0.94 d
3
[6H, CH(CH3)2, J = 6.8 Hz], 1.23 br (2H, NH2),
1.35 d.d (1H, 3-H, 2J = 13.4, 3J = 11.5 Hz), 1.62 sept.d
3
[1H, CH(CH3)2, J = 6.8, 5.6 Hz], 1.72 t.d (1H, 5-H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

SYNTHESIS AND SOME TRANSFORMATIONS OF 4-ARYL-SUBSTITUTED AMINES
117
3
2J = 12.3, J = 5.3 Hz), 1.83–1.94 m (2H, 3-H, 5-H),
7.14 m (6H) (Harom). Found, %: C 78.62; H 9.22;
N 3.59. C25H35NO2. Calculated, %: C 78.70; H 9.25;
N 3.67.
2.18–2.26 m (4H, CH2CH2NH2), 2.31 s (3H,
CH3C6H4), 3.31 d.d.d (1H, 2-H, 3J = 11.5, 5.6, 1.5 Hz),
2
3
3.73 d.d.d (1H, 6-H, J = 12.0, J = 12.3, 1.9 Hz),
N-(3,4-Dimethoxybenzyl)-2-[2-isopropyl-4-(4-
tolyl)tetrahydropyran-4-yl]ethanamine (IX). Yield
77%, bp 226–230°C (1 mm). IR spectrum: ν 3300 cm–1
2
3
3.85 d.d.d (1H, J = 12.0, J = 5.2, 1.3 Hz), 7.06 m
(2H) and 7.12 m (2H) (C6H4). Found, %: C 78.00;
H 10.51; N 5.27. C17H27NO·HCl. Calculated, %:
C 78.11; H 10.41; N 5.35.
1
(NH). H NMR spectrum, δ, ppm: 0.91 d (3H, CH3,
3
3J = 6.8 Hz), 0.92 d (3H, CH3, J = 6.8 Hz), 1.12 br
(1H, NH), 1.35 d.d (1H, 3-H, 2J = 12.7, 3J = 11.8 Hz),
N-Arylmethylidene-2-[2-isopropyl-4-(4-tolyl)-
tetrahydropyran-4-yl]ethanamines VII–XI (general
procedure). A mixture of equimolar amounts
(0.01 mol) of amine II and aromatic aldehyde in 50 ml
of benzene was heated for 4 h under reflux in a flask
equipped with a Dean–Stark trap until complete re-
moval of water. The solvent was removed, the residue
was dissolved in methanol, and an equivalent amount
of NaBH4 was added in portions under stirring and
cooling with water, maintaining the temperature below
20°C. The mixture was then stirred for 1 h at room
temperature, the solvent was distilled off, and the resi-
due was made alkaline by adding a 20% solution of
sodium hydroxide and extracted with benzene. The
extract was dried, the solvent was distilled off, and
amines VII–XI were isolated from the residue by
distillation.
3
3
1.60 sept.d [1H, CH(CH3)2, J = 6.8, J = 5.8 Hz],
2
3
1.69 t.d (1H, 3-H, J = 13.2, J = 12.8, 5.3 Hz), 1.83–
1.94 m (2H, 3-H, 5-H), 1.97 m (2H, CH2CH2NH),
2.17 m (2H, CH2CH2NH), 2.31 s (3H, C6H4CH3),
3.29 d.d.d (1H, 2-H, 3J = 11.8, 5.8, 1.6 Hz), 3.45 s (2H,
C6H3CH2), 3.72 m (1H, 6-H), 3.75 s (3H, OCH3),
3.76 s (3H, OCH3), 3.85 d.d.d (1H, 6-H, 2J = 11.8, 3J =
5.2, 1.4 Hz), 6.62 d.d (1H, 6′-H, 3J = 8.1, 4J = 2.0 Hz),
3
4
6.69 d (1H, 5′-H, J = 8.1 Hz), 6.75 d (1H, 2′-H, J =
2.0 Hz), 7.05 m and 7.11 m (2H each, C6H4). Found,
%: C 75.76; H = 8.95; N 3.50. C26H37NO3. Calculated,
%: C 75.87; H 9.06; N 3.40.
N-(2-Fluorobenzyl)-2-[2-isopropyl-4-(4-tolyl)-
tetrahydropyran-4-yl]ethanamine (X). Yield 85%,
bp 200–204°C (1 mm). IR spectrum: ν 3340–
1
3310 cm–1 (NH). H NMR spectrum, δ, ppm: 0.92 d
(3H, CH3, 3J = 6.8 Hz), 0.93 d (3H, CH3, 3J = 6.8 Hz),
N-Benzyl[2-isopropyl-4-(4-tolyl)tetrahydropyr-
an-4-yl]ethanamine (VII). Yield 83%, bp 198–200°C
(1 mm). IR spectrum: ν 3320–3310 cm–1 (NH). 1H NMR
2
3
1.28 br (1H, NH), 1.36 d.d (1H, 3-H, J = 13.0, J =
11.7 Hz), 1.62 sept.d [1H, CH(CH3)2, 3J = 6.8, 5.8 Hz],
1.71 t.d (1H, 3-H, 2J = 12.5, 3J = 5.1 Hz), 1.83–1.96 m
(2H, 3-H, 5-H), 1.99 m (2H, CH2CH2NH), 2.20 m
(2H, CH2CH2NH), 2.32 s (3H, C6H4CH3), 3.29 d.d.d
3
spectrum, δ, ppm: 0.91 d (3H, CH3, J = 6.8 Hz),
3
0.92 d (3H, CH3, J = 6.8 Hz), 1.15 br (1H, NH),
1.35 d.d (1H, 3-H, 2J = 12.7, 3J = 11.7 Hz), 1.61 sept.d
3
3
(1H, 2-H, J = 11.6, 5.8, 1.5 Hz), 3.60 s (2H,
[1H, CH(CH3)2, J = 6.8, 5.8 Hz], 1.70 t.d (1H, 3-H,
2
3
3
2J = 12.7, J = 5.1 Hz), 1.83–1.93 m (2H, 3-H, 5-H),
C6H4CH2), 3.73 d.d.d (1H, 6-H, J = 11.9, J = 12.5,
2
3
2.1 Hz), 3.86 d.d.d (1H, 6-H, J = 11.9, J = 5.3,
1.7 Hz), 6.92–7.25 m (8H, Harom). Found, %: C 77.90;
H 8.64; N 3.71. C24H32FNO. Calculated, %: C 78.01;
H 8.73; N 3.79.
1.97 m (2H, CH2CH2NH), 2.19 m (2H, CH2CH2NH),
3
2.32 s (3H, C6H4CH3), 3.28 d.d.d (1H, 2-H, J = 11.7,
5.8, 1.6 Hz), 3.54 s (2H, PhCH2), 3.72 d.d.d (1H, 6-H,
2J = 11.8, 3J = 12.6, 1.9 Hz), 3.85 d.d.d (1H, 6-H, 2J =
3
11.8, J = 5.2, 1.5 Hz), 7.04–7.23 m (9H, Harom).
N-(Furan-2-ylmethyl)-2-[2-isopropyl-4-(4-tolyl)-
tetrahydropyran-4-yl]ethanamine (XI). Yield 87%,
bp 191–194°C (2 mm). IR spectrum: ν 3320 cm–1
Found, %: C 82.11; H 9.37; N 4.06. C24H33NO. Calcu-
lated, %: C 82.00; H 9.46; N 3.98.
1
(NH). H NMR spectrum, δ, ppm: 0.91 d (3H, CH3,
2-[2-Isopropyl-4-(4-tolyl)tetrahydropyran-4-yl]-
N-(4-methoxybenzyl)ethanamine (VIII). Yield 80%,
bp 218–220°C (1 mm). IR spectrum: ν 3330 cm–1
(NH). 1H NMR spectrum, δ, ppm: 0.92 d (3H, CH3, J =
6.8 Hz), 0.94 d (3H, CH3, J = 6.8 Hz), 1.12 br (1H,
NH), 1.36 d.d (1H, CH2, J = 12.8, 11.8 Hz), 1.62 m
[1H, CH(CH3)2], 1.70 t.d (1H, CH2, J = 12.8, 5.1 Hz),
1.83–2.00 m (6H, CH2), 2.12–2.21 m (2H, CH2), 2.33 s
(3H, C6H4CH3), 3.29 d.d.d (1H, OCH, J = 11.5, 5.9,
1.2 Hz), 3.47 s (2H, C6H4CH2), 3.68–3.89 m (2H,
OCH2), 3.75 s (3H, OCH3), 6.73 m (2H) and 7.03–
3
3J = 6.8 Hz), 0.92 d (3H, CH3, J = 6.8 Hz), 1.30 br
(1H, NH), 1.34 d.d (1H, 3-H, 2J = 12.8, 3J = 11.6 Hz),
3
1.60 sept.d [1H, CH(CH3)2, J = 6.8, 5.8 Hz], 1.69 t.d
2
3
(1H, 3-H, J = 12.7, J = 5.2 Hz), 1.82–1.92 m (2H,
3-H, 5-H), 1.93 m (2H, CH2CH2NH), 2.16 m (2H,
CH2CH2NH), 2.31 s (3H, C6H4CH3), 3.28 d.d.d (1H,
2-H, 3J = 11.6, 5.8, 1.7 Hz), 3.51 s (2H, C4H3OCH2),
2
3
3.71 d.d.d (1H, 6-H, J = 11.8, J = 12.7, 1.6 Hz),
3.84 d.d.d (1H, 6-H, 2J = 11.8, 3J = 5.2, 1.6 Hz), 5.97 d
(1H, 3′-H, J = 3.2 Hz), 6.21 d.d (1H, 4′-H, J = 3.2,
3
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

ARUTYUNYAN et al.
118
2.0 Hz), 7.05 m and 7.11 m (2H each, C6H4), 7.28 d
(1H, 5′-H, J = 2.0 Hz). Found, %: C 77.41; H 9.06;
N 4.02. C22H31NO2. Calculated, %: C 77.38; H 9.15;
N 4.10.
N-{2-[2-Isopropyl-4-(4-tolyl)tetrahydropyran-4-
yl]ethyl}-N-(4-methoxybenzyl)acetamide (XIV).
Yield 67% (a mixture of four diastereoisomers),
bp 240–244°C (1 mm). IR spectrum, ν, cm–1: 3280
(NH), 1650 (amide I). 1520 (amide II). 1H NMR spec-
trum, δ, ppm: 0.89–0.93 m [6H, (CH3)2CH, J =
6.9 Hz], 1.28–1.38 m (1H, 3-H), 1.52–1.99 m [6H,
5-H, (CH3)2CH, CH2CH2N], 1.72 s (1.8H) and 1.97 s
(1.2H) (CH3CO), 2.32 s (1.2H) and 2.35 s (1.8H,
C6H4CH3), 2.59–2.87 m (2H, CH2CH2N), 3.18 d.d.d
3
N-Benzyl-N-{2-[2-isopropyl-4-(4-tolyl)tetrahy-
dropyran-4-yl]ethyl}acet(propion)amides XII–XXI
(general procedure). Acetyl or propionyl chloride,
0.03 mol, was added to a solution of 0.03 mol of amine
VII–XI and 3 g (0.032 mol) of triethylamine in 30 ml
of anhydrous benzene. The mixture was heated for 4 h
under reflux, cooled, washed with water, and extracted
with benzene, the solvent was distilled off, and the
residue was distilled under reduced pressure to isolate
amides XII–XXI.
3
(0.6H, J = 11.8, 5.8, 1.0 Hz) and 3.25 d.d.d (0.4H,
3J = 11.8, 5.8, 1.0 Hz) (2-H), 3.58–3.73 m and 3.79–
3.88 m (1H each, 6-H), 3.75 s (1.8H ) and 3.75 s
2
(1.2H) (CH3O); 4.13 d (0.4H, J = 11.7 Hz), 4.16 d
2
2
(0.4H, J = 11.7 Hz), 4.19 d (0.6H, J = 14.2 Hz), and
2
N-Benzyl-N-{2-[2-isopropyl-4-(4-tolyl)tetrahy-
dropyran-4-yl]ethyl}acetamide (XII). Yield 73%
(a mixture of four diastereoisomers), bp 220–225°C
(0.5 mm). IR spectrum, ν, cm–1: 3280 (NH), 1640
(amide I), 1520 (amide II). 1H NMR spectrum, δ, ppm:
0.89–0.94 m [6H, (CH3)2CH, J = 6.9 Hz], 1.26–1.38 m
(1H, 3-H), 1.52–1.89 m [4H, (CH3)2CH, 5-H), 1.75 s
(1.8H) and 1.97 s (1.2H (COCH3), 1.91–2.02 m (2H,
CH2CH2N), 2.31 s (1.2H) and 2.34 s (1.8H)
(C6H4CH3), 2.65–2.76 m (1.2H) and 2.77–2.89 m
4.28 d (0.6H, J = 14.2 Hz) (C6H4CH2); 6.68–6.75 m
(2H), 6.82–6.89 m (2H), and 7.04–7.14 m (4H) (Harom).
Found, %: C 76.67; H 8.71; N 3.23. C27H37NO3. Cal-
culated, %: C 76.56; H 8.80; N 3.31.
N-{2-[2-Isopropyl-4-(4-tolyl)tetrahydropyran-4-
yl]ethyl}-N-(4-methoxybenzyl)propionamide (XV).
Yield 65% (a mixture of two diastereoisomers),
bp 243–245°C (0.5 mm). IR spectrum, ν, cm–1: 3275
1
(NH), 1650 (amide I), 1510 (amide II). H NMR spec-
trum, δ, ppm: 0.89–0.93 m [6H, (CH3)2CH, J =
3
3
(0.8H) (CH2CH2N), 3.17 d.d.d (0.6H, J = 11.6, 5.9,
6.9 Hz], 0.95 t (1.8H, J = 7.3 Hz) and 1.03 t (1.2H,
3
3J = 7.3 Hz) (CH3CH2CO), 1.28–1.38 m (1H, 3-H),
1.52–1.97 m [6H, 5-H, (CH3)2CH, CH2CH2N], 1.91 q
1.2 Hz) and 3.26 d.d.d (0.4H, J = 11.6, 5.9, 1.2 Hz)
(2-H), 3.57–3.73 m and 3.80–3.87 m (1H each, 6-H);
2
2
3
3
4.22 d (0.4H, J = 12.1 Hz), 4.24 d (0.4H, J =
(1.2H, J = 7.3 Hz) and 2.24 q (0.8H, J = 7.3 Hz)
(CH3CH2CO), 2.32 s (1.2H) and 2.35 s (1.8H)
(C6H4CH3), 2.61–2.87 m (2H, CH2CH2N), 3.17 d.d.d
2
12.1 Hz), 4.29 d (0.6H, J = 14.5 Hz), and 4.36 d
(0.6H, J = 14.5 Hz) (PhCH2); 6.94–7.24 m (9H,
2
3
Harom). Found, %: C 79.42; H 9.03; N 4.00. C26H35NO2.
Calculated, %: C 79.35; H 8.96; N 3.56.
(0.6H, J = 11.5, 5.8, 1.2 Hz) and 3.26 d.d.d (0.4H,
3J = 11.5, 5.8, 1.2 Hz) (2-H), 3.58–3.73 m and 3.78–
3.88 m (1H each, 6-H), 3.75 s (3H, CH3O); 4.15 s
N-Benzyl-N-{2-[2-isopropyl-4-(4-tolyl)tetrahy-
dropyran-4-yl]ethyl}propionamide (XIII). Yield
70% (a mixture of four diastereoisomers), bp 230–
234°C (1 mm). IR spectrum, ν, cm–1: 3380 (NH), 1637
(amide I), 1510 (amide II). 1H NMR spectrum, δ, ppm:
0.89–0.94 m [6H, (CH3)2CH, J = 6.9 Hz], 0.97 t (1.8H,
2
(0.8H), 4.19 d (0.6H, J = 14.3 Hz), and 4.29 d (0.6H,
2J = 14.3 Hz) (C6H4CH2); 6.67–6.75 m (2H), 6.80–
6.88 m (2H), 7.03–7.10 m (1.6H), and 7.11 s (2.4H)
(Harom). Found, %: C 77.57; H 8.00; N 3.22. C28H39NO3.
Calculated, %: C 77.64; H 7.92; N 3.11.
3
3J = 7.3 Hz) and 1.03 t (1.2H, J = 7.3 Hz)
N-(4-Isopropoxybenzyl)-N-{2-[2-isopropyl-4-(4-
tolyl)tetrahydropyran-4-yl]ethyl}acetamide (XVI).
Yield 68% (a mixture of two diastereoisomers),
bp 242–246°C (0.5 mm). IR spectrum, ν, cm–1: 3280
(CH3CH2CO), 1.29–1.38 m (1H, 3-H), 1.52–2.00 m
3
[6H, 5-H, (CH3)2CH, CH23CH2N], 1.94 q (1.2H, J =
7.3 Hz) and 2.23 q (0.8H, J = 7.3 Hz) (CH3CH2CO),
2.31 s (1.2H) and 2.35 s (1.8H) (C6H4CH3), 2.62–
1
(NH), 1640 (amide I), 1520 (amide II). H NMR spec-
3
2.89 m (2H, CH2CH2N), 3.17 d.d.d (0.6H, J = 11.5,
trum, δ, ppm: 0.89–0.93 m [6H, (CH3)2CH, J =
6.9 Hz], 1.26–1.39 m (1H, 3-H), 1.30 d [6H,
(CH3)2CHO, J = 6.1 Hz], 1.50–1.97 m [6H, 5-H,
(CH3)2CH, CH2CH2N], 1.72 s (2H) and 2.00 s (1H)
(CH3CO); 2.31 s, 2.32 s, and 2.35 s (3H, C6H4CH3);
2.65–2.89 m (2H, CH2CH2N), 3.18 (1.3H) and
3.25 d.d.d (0.7H, 3J = 11.5, 5.9, 1.3 Hz) (2-H), 3.62 t.d
3
5.7, 1.2 Hz) and 3.26 d.d.d (0.4H, J = 11.5, 5.7,
1.2 Hz) (2-H), 3.57–3.74 m and 3.80–3.87 m (1H each,
2
6-H); 4.23 s (0.8H), 4.29 d (0.6H, J = 14.5 Hz), and
2
4.37 d (0.6H, J = 14.5 Hz) (PhCH2); 6.93–7.26 m
(9H, Harom). Found, %: C 79.64; H 9.03; N 3.38.
C27H37NO2. Calculated, %: C 79.56; H 9.15; N 3.44.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

SYNTHESIS AND SOME TRANSFORMATIONS OF 4-ARYL-SUBSTITUTED AMINES
119
2
3
3
(0.6H) and 3.67 t.d (0.4H, J = 12.0, J = 2.1 Hz)
(6-H), 3.79–3.87 m (1H, 6-H); 4.12 d and 4.15 d (0.4H
each, 2J = 12.8 Hz), 4.18 d and 4.28 d (0.6H each, 2J =
14.3 Hz) (C6H4CH2); 4.50 m (1H, OCH); 6.64–6.73 m
(2H), 6.80–6.87 m (2H), and 7.04–7.15 m (4H) (Harom).
Found, %: C 77.00; H 9.21; N 3.02. C29H41NO3. Cal-
culated, %: C 77.12; H 9.15; N 3.10.
(CH3CH2CO, J = 7.3 Hz), 2.31 s (1.2H) and 2.32 s
(1.8H (C6H4CH3), 2.69–2.92 m (2H, CH2CH2N),
3
3
3.20 d.d.d (0.6H) and 3.27 d.d.d (0.4H, J = 11.4, J =
3
5.8, J = 1.2 Hz) (2-H), 3.64 t.d (0.6H) and 3.69 t.d
(0.4H, 2J = 11.9, 3J = 2.1 Hz) (6-H), 3.80–3.88 m (1H,
6-H), 4.29 s (0.8H) and 4.46 s (1.2H (C6H4CH2), 6.82–
7.28 m (8H, Harom). Found, %: C 76.11; H 8.60; N 3.36.
C27H36FNO2. Calculated, %: C 76.20; H 8.53; N 3.29.
N-(4-Isopropoxybenzyl)-N-{2-[2-isopropyl-4-
(4-tolyl)tetrahydropyran-4-yl]ethyl}propionamide
(XVII). Yield 63%, bp 247–249°C (0.5 mm). IR spec-
trum, ν, cm–1: 3270 (NH), 1655 (amide I), 1515 (amide
II). H NMR spectrum, δ, ppm: 0.89–0.93 m [6H,
(CH3)2CH, J = 6.8 Hz], 0.95 t (2H) and 1.03 t (1H)
(CH3CH2CO, J = 7.3 Hz), 1.26–1.38 m (1H, 3-H),
1.30 d [6H, (CH3)2CHO, J = 6.0 Hz], 1.50–1.97 m
[6H, 5-H, (CH3)2CH, CH2CH2N], 1.91 q (1.3H) and
N-(Furan-2-ylmethyl)-N-{2-[2-isopropyl-4-(4-
tolyl)tetrahydropyran-4-yl]ethyl}acetamide (XX).
Yield 70% (a mixture of two diastereoisomers),
bp 210–213°C (1 mm). IR spectrum, ν, cm–1: 3300
(NH), 1635 (amide I), 1520 (amide II). H NMR spec-
trum, δ, ppm: 0.91 d (3.2H) and 0.92 d (2.8H)
1
1
3
3
[(CH3)2CH, J = 6.7 Hz], 1.28–1.39 m (1H, 3-H),
1.54–1.74 m [2H, CH(CH3)2, 3-H], 1.64 s (1.6H) and
2.04 s (1.4H) (CH3CO), 1.78–1.95 m (4H, 5-H,
CH2CH2N), 2.33 s (3H, C6H4CH3), 2.73–2.86 m (2H,
CH2CH2N), 3.24 m (1H, 2-H), 3.67 m and 3.84 m (1H
each, 6-H); 4.15 s (~1H), 4.34 d (0.5H), and 4.36 d
3
2.24 q (0.7H) (CH3CH2CO, J = 7.3 Hz); 2.30 s,
2.32 s, and 2.35 s (3H) (C6H4CH3); 2.64–2.89 m (2H,
CH2CH2N), 3.17 d.d.d (0.6H) and 3.25 d.d.d (0.4H,
3J = 11.4, 5.9, 1.2 Hz) (2-H), 3.57–3.73 m and 3.79–
3.88 m (1H each, 6-H); 4.14 s (0.6H), 4.18 d (0.6H,
2
(0.5H, J = 15.2 Hz) (C4H3OCH2); 5.91 d and 6.04 d
(0.5H each, 3′-H, J = 3.3 Hz), 6.25 m (1H, 4′-H),
3
2J = 14.2 Hz), and 4.29 d (0.6H, J = 14.2 Hz)
2
7.06–7.15 m (4H, Harom), 7.33 d and 7.36 d (0.5H each,
5′-H, 3J = 1.7 Hz). Found, %: C 75.10; H 8.58; N 3.58.
C24H33NO3. Calculated, %: C 75.16; H 8.67; N 3.65.
(C6H4CH2); 4.49 m (1H, OCH); 6.63–6.72 m (2H),
6.78–6.86 m (2H), and 7.04–7.14 m (4H) (Harom).
Found, %: C 77.47; H 9.23; N 3.08. C30H43NO3. Cal-
culated, %: C 77.38; H 9.31; N 3.01.
N-(Furan-2-ylmethyl)-N-{2-[2-isopropyl-4-
(4-tolyl)tetrahydropyran-4-yl]ethyl}propionamide
(XXI). Yield 78%, bp 220–222°C (1 mm). IR spec-
trum, ν, cm–1: 3380 (NH), 1650 (amide I), 1520 (amide
N-(2-Fluorobenzyl)-N-{2-[2-isopropyl-4-(4-tolyl)-
tetrahydropyran-4-yl]ethyl}acetamide (XVIII).
Yield 66%, bp 220–223°C (1.5 mm). IR spectrum, ν,
cm–1: 3380 (NH), 1660 (amide I), 1520 (amide II).
1H NMR spectrum, δ, ppm: 0.89–0.93 m [6H,
(CH3)2CH, J = 6.9 Hz], 1.26–1.39 m (1H, 3-H), 1.52–
2.04 m [6H, 5-H, (CH3)2CH, CH2CH2N], 1.68 s (1.8H)
and 1.98 s (1.2H) (CH3CO), 2.31 s (3H, C6H4CH3),
2.68–2.89 m (2H, CH2CH2N), 3.20 d.d.d (0.6H) and
3.26 d.d.d (0.4H, 3J = 11.7, 5.8, 1.4 Hz) (2-H), 3.63 t.d
1
II). H NMR spectrum, δ, ppm: 0.89–0.94 m
3
[(CH3)2CH, J = 6.8 Hz], 0.95 t (2H) and 1.03 t (1H)
3
(CH3CH2CO, J = 7.3 Hz), 1.26–1.38 m (1H, 3-H),
3
1.31 d (6H, CH3, J = 6.1 Hz), 1.50–1.97 m [6H,
CH(CH3)2, 5-H, CH2CH2N], 1.91 q (1.3H) and 2.24 q
3
(0.7H) (CH3CH2CO, J = 7.3 Hz); 2.30 s, 2.32 s, and
2.35 s (3H, C6H4CH3), 2.64–2.89 m (2H, CH2CH2N),
3
2
3
3.17 d.d.d (0.6H) and 3.25 d.d.d (0.4H, J = 11.4, 5.9,
(0.6H) and 3.68 t.d (0.4H, J = 12.0, J = 2.1 Hz)
(6-H), 3.80–3.88 m (1H, 6-H), 4.28 s (0.8H) and 4.44 s
(1.2H) (C6H4CH2), 6.82–7.29 m (8H, Harom). Found,
%: C 75.91; H 8.41; N 3.32. C26H34FNO2. Calculated,
%: C 75.88; H 8.33; N 3.40.
1.2 Hz) (2-H), 5.91 d and 6.04 d (0.5H each, 3-H, 3J =
3.3 Hz), 6.25 m (1H, 4′-H), 7.06–7.15 m (4H, Harom),
3
7.33 d and 7.36 d (0.5H each, 5′-H, J = 1.7 Hz).
Found, %: C 75.42; H 8.79; N 3.63. C25H35NO3. Cal-
culated, %: C 75.53; H 8.87; N 3.52.
N-(2-Fluorobenzyl)-N-{2-[2-isopropyl-4-(4-tolyl)-
tetrahydropyran-4-yl]ethyl}propionamide (XIX).
Yield 64%, bp 223–226°C (1.5 mm). IR spectrum, ν,
cm–1: 3280 (NH), 1640 (amide I), 1510 (amide II).
1H NMR spectrum, δ, ppm: 0.90–0.94 m [6H,
(CH3)2CH, J = 6.7 Hz], 0.93 t (1.8H) and 1.03 t (1.2H)
REFERENCES
1. Arutyunyan, N.S., Akopyan, L.A., Akopyan, N.Z., Ge-
vorgyan, G.A., and Panosyan, G.A., Khim. Geterotsikl.
Soedin., 2010, p. 835.
2. Arutyunyan, N.S., Akopyan, L.A., Gevorgyan, G.A.,
Snkhchyan, G.M., and Panosyan, G.A., Khim. Geterotsikl.
Soedin., 2005, p. 517.
3
(CH3CH2CO, J = 7.3 Hz), 1.27–1.40 m (1H, 3-H),
1.53–1.74 m [2H, CH(CH3)2, 3-H], 1.78–2.03 m (4H,
5-H, CH2CH2N), 1.86 q (1.2H) and 2.24 q (0.8H)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011