2392
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 10, October, 2014
Makarov et al.
1
4
3
.00 (s, 4 H, OCH CH O). 13C NMR, : 31.34 (C(6), C(10));
633, 621, 559, 490, 457. H NMR, : 2.76 (t, 2 H, NCH CH N ,
2 2 3
2
2
3
3
7.55 (CH Cl); 51.12 (C(7), C(9)); 56.94 (NCH CH Cl); 64.76
JH,H = 5.9 Hz); 3.29 (t, 2 H, NCH CH N , J
3.89 (s, 4 H, C(2)H , C(6)H ); 7.46 (d, 4 H, C H , J
2 2 6 4 H,H
= 8.2 Hz); 7.79 (s, 2 H, =CH—CAr).
H,H
C NMR, : 48.73 (CH N ); 54.39 (C(2), C(6)); 55.29
= 5.9 Hz);
= 8.2 Hz);
2
2
2
2
2
3
H,H
3
and 64.91 (OCH CH O); 104.15 (O—C—O).
2
2
3
8ꢀ(2ꢀAzidoethyl)ꢀ1,4ꢀdioxaꢀ8ꢀazaspiro[4,5]decane (4). A mixꢀ
7.72 (d, 4 H, C H , J
6
4
1
3
ture of 8ꢀ(2ꢀchloroethyl)ꢀ1,4ꢀdioxaꢀ8ꢀazaspiro[4,5]decane
hydrochloride (6.15 g, 0.0254 mol) and sodium azide (5.0 g,
2 3
(CH CH N ); 112.53 (C —CN); 118.22 (CN); 130.46 (C H);
2
2
3
Ar
Ar
0
.077 mol) in water (30 mL) was heated at 77 C (the bath
132.28 (C H); 134.78 (C —CH=); 135.03 (C —CH=); 139.17
Ar Ar Ar
temperature) with stirring for 19 h. Then, the reaction solution
(C —CH=C); 185.96 (C=O).
Ar
was cooled to room temperature and filtered, a solution of NaOH
1ꢀ(2ꢀAzidoethyl)ꢀ3,5ꢀbis(4ꢀnitrobenzylidene)ꢀ4ꢀpiperidinone
(6b). Purification by column chromatography (gradient elution
from CHCl to CHCl —EtOH (100 : 0.5)) with subsequent reꢀ
(
1.04 g, 0.026 mol) in water (10 mL) was added to the filtrate.
The reaction mixture was extracted with Et O (~150 mL), the
2
3
3
organic phase was separated, dried with Na SO , filtered, and
precipitation by a slow diffusion of pentane into the solution of 6b
in acetone. The yield was 33%, m.p. 165 C (decomp.).
Found (%): C, 58.09; H, 4.21; N, 19.44. C H N O . Calculatꢀ
2
4
concentrated at reduced pressure to obtain the target product as
a light yellow liquid (4.77 g, 88%), which was used in the followꢀ
ing step without additional purification. Found (%): C, 50.99;
H, 7.46; N, 26.64. C H N O . Calculated (%): C, 50.93; H, 7.60;
21
18
6
5
–
1
ed (%): C, 58.06; H, 4.18; N, 19.35. IR (KBr), /cm : 3101,
3065, 2928, 2841, 2748, 2109 (N ), 1670, 1615, 1599, 1579, 1517
9
16
4
2
3
1
3
N, 26.40. H NMR, : 1.71 (t, 4 H, C(6)H , C(10)H , J
6.0 Hz); 2.54 (t, 4 H, C(7)H , C(9)H , J = 6.0 Hz); 2.57
H,H
=
(NO ), 1493, 1450, 1412, 1344 (NO ), 1305, 1280, 1261, 1216,
2
2
H,H
2
2
3
=
(
3
1190, 1153, 1110, 1062, 1013, 991, 941, 884, 858, 848, 811, 757,
2
2
3
1
t, 2 H, NCH CH N , J
= 6.0 Hz); 3.29 (t, 2 H, NCH CH N ,
714, 687, 599, 500, 444. H NMR, : 2.78 (t, 2 H, NCH CH N ,
2
2
3
H,H
2
2
3
2
2
3
13
3
3
JH,H = 6.0 Hz); 3.90 (s, 4 H, OCH CH O). C NMR,
JH,H = 5.8 Hz); 3.30 (t, 2 H, NCH CH N , J
3.91 (s, 4 H, C(2)H , C(6)H ); 7.53 (d, 4 H, C H , J
2 2 6 4 H,H
= 5.8 Hz);
= 8.7 Hz);
= 8.7 Hz).
H,H
2
2
2
2
3
H,H
3
: 34.79 (C(6), C(10)); 48.62 (CH N ); 51.46 (C(7), C(9)); 56.81
2
3
3
(
NCH CH N ); 64.27 (OCH CH O); 107.12 (O—C—O).
7.83 (s, 2 H, =CH—C ); 8.28 (d, 4 H, C H , J
2
2
3
2
2
Ar
6
4
1
3
1
ꢀ(2ꢀAzidoethyl)piperidinꢀ4ꢀone (5). A stirring mixture of
C NMR, : 48.67 (CH N ); 54.39 (C(2), C(6)); 55.33
2 3
8
0
ꢀ(2ꢀazidoethyl)ꢀ1,4ꢀdioxaꢀ8ꢀazaspiro[4,5]decane (4.7 g,
.022 mol), glacial acetic acid (22 mL), and 37% aqueous HCl
(CH CH N ); 123.78 (C H); 130.71 (C H); 134.62 (C —CH=);
2 2 3 Ar Ar Ar
135.16 (CAr—CH=); 141.03 (C —CH=C); 147.55 (C —NO );
Ar
Ar
2
(
28 mL) was heated at 70 C (the bath temperature) for 35 h. The
185.87 (C=O).
volatile components were removed at reduced pressure, the resꢀ
idue was dissolved in water (15 mL), an aq. solution of NaHCO3
1ꢀ(2ꢀAzidoethyl)ꢀ3,5ꢀbis[(pyridinꢀ3ꢀyl)methylidene]ꢀ4ꢀpiperiꢀ
dinone (6c). Purification by column chromatography (gradient
elution from CHCl to CHCl —EtOH (100 : 5)). The yield was
(
1.85 g, 50 mL) was added to reach pH 8. The aqueous phase
3
3
was extracted with CH Cl . The organic phase was separated,
31%, m.p. 114—118 C (decomp.). Found (%): C, 65.85; H, 5.05;
2
2
dried with Na SO , and filtered. The solvent was evaporated on
N, 24.38. C H N O. Calculated (%): C, 65.88; H, 5.24;
N, 24.26. IR (KBr), /cm : 3082, 3046, 2933, 2885, 2820, 2752,
2
4
19 18
6
–1
a rotary evaporator to obtain the target compound as a clear light
yellow liquid (3.70 g, 99%). Found (%): C, 50.27; H, 7.11; N, 33.19.
C H N O. Calculated (%): C, 49.99; H, 7.19; N, 33.31.
2102 (N ), 1674, 1617, 1588, 1580, 1560, 1478, 1458, 1413,
3
1340, 1327, 1305, 1275, 1244, 1208, 1198, 1179, 1156, 1133,
1107, 1061, 1020, 988, 982, 959, 882, 824, 813, 770, 704, 636,
7
12
4
1
3
H NMR, : 2.45 (t, 4 H, C(3)H , C(5)H , J = 6.1 Hz); 2.71
t, 2 H, NCH CH N , J
C(6)H , J
2
2
H,H
3
1
(
= 5.8 Hz); 2.80 (t, 4 H, C(2)H ,
= 6.1 Hz); 3.36 (t, 2 H, NCH CH N , J
618, 556, 547, 509. H NMR, : 2.76 (t, 2 H, NCH CH N ,
2
2
3
H,H
2
=
2
2
3
3
3
3
3
JH,H = 5.9 Hz); 3.28 (t, 2 H, NCH CH N , J = 5.8 Hz);
3.90 (s, 4 H, C(2)H , C(6)H ); 7.35 (dd, 2 H, PyH, J = 4.8 Hz,
2 2 H,H
JH,H = 7.9 Hz); 7.67 (d, 2 H, PyH, JH,H = 8.0 Hz); 7.77
(s, 2 H, =CH—C ); 8.58 (dd, 2 H, PyH, JH,H = 4.9 Hz,
2
H,H
2
2
3
H,H
2
2
3
H,H
3
13
=
5.8 Hz). C NMR, : 40.76 (C(3), C(5)); 48.22 (CH N );
2
3
3
3
5
2.66 (C(2), C(6)); 55.77 (NCH CH N ); 208.15 (C=O).
2
2
3
3
Synthesis of compounds 6a—d (general procedure). Azide 5
5.3 mmol) and the corresponding aldehyde (10.6 mmol) were
mixed in a flask, followed by addition of diethylamine (0.78 g,
0.7 mmol) and lithium perchlorate (0.56 g, 5.3 mmol). The
Ar
4
4
13
(
JH,H = 1.6 Hz); 8.63 (d, 2 H, PyH, J
= 2.1 Hz). C NMR,
H,H
: 48.46 (CH N ); 54.29 (C(2), C(6)); 55.22 (CH CH N );
2
3
2
2
3
1
123.30 (CPyH); 130.58 (=CH—CPy); 133.26 (C=CH—CPy);
134.08 (C=CH—CPy); 136.86 (CPyH); 149.61 (CPyH); 150.73
(CPyH); 185.71 (C=O).
reaction mixture was stirred at room temperature until it became
dense and allowed to stand for 16 h at room temperature. Then,
the mixture was diluted with water and CH Cl . The organic
1ꢀ(2ꢀAzidoethyl)ꢀ3,5ꢀbis(4ꢀdimethylaminobenzylidene)ꢀ4ꢀ
piperidinone (6d). Purification by recrystallization from a mixꢀ
ture of toluene—hexane. The yield was 56%, m.p. 176–178 C
(decomp.). Found (%): C, 69.65; H, 7.14; N, 19.44. C H N O.
2
2
solution was separated, dried with Na SO , and filtered. The
2
4
solvent was evaporated on a rotary evaporator to obtain a crude
product as yellow (compounds 6a—c) or red (compound 6d)
solid compounds, which were purified by column chromatography
and, if neccesary, by subsequent recrystallization (reprecipꢀ
itation) (purification conditions for each compound are given below).
2
5
30
6
–
1
Calculated (%): C, 69.74; H, 7.02; N, 19.52. IR (KBr), /cm
:
3093, 2910, 2881, 2810, 2100 (N ), 1659, 1587, 1522, 1445,
3
1432, 1367, 1305, 1283, 1230, 1182, 1169, 1146, 1102, 1059,
1
1
ꢀ(2ꢀAzidoethyl)ꢀ3,5ꢀbis(4ꢀcyanobenzylidene)ꢀ4ꢀpiperidinone
6a). Purification by column chromatography (gradient elution
from CHCl to CHCl —EtOH (100 : 1)). The yield was 52%,
992, 939, 913, 874, 813, 777, 657, 527, 512, 460. H NMR,
3
(
: 2.78 (t, 2 H, NCH CH N , J
= 6.2 Hz); 3.02 (s, 12 H,
2
2
3
H,H
3
NMe ); 3.31 (t, 2 H, NCH CH N , J
C(2)H , C(6)H ); 6.71 (d, 4 H, C H , JH,H= 8.8 Hz); 7.33
(d, 4 H, C H , JH,H = 8.8 Hz); 7.80 (s, 2 H, =CH—CAr).
6 4
C NMR, : 39.85 (Me); 48.71 (CH N ); 54.63 (C(2), C(6));
= 6.2 Hz); 3.96 (s, 4 H,
3
3
3
2
2
2
3
H,H
m.p. 180—182 C (decomp.). Found (%): C, 69.96; H, 4.41;
2
2
6
4
3
N, 21.40. C23H18N O. Calculated (%): C, 70.04; H, 4.60;
6
–
1
13
N, 21.31. IR (KBr), /cm : 3076, 3061, 3042, 3023, 2950, 2924,
2 3
2
1
1
854, 2806, 2745, 2230 (CN), 2101 (N ), 1673, 1613, 1586, 1505,
459, 1414, 1386, 1352, 1327, 1308, 1288, 1271, 1222, 1191,
171, 1156, 1121, 1066, 1015, 985, 958, 940, 880, 834, 777, 652,
54.84 (CH CH N ); 111.46 (CArH); 122.95 (CAr—CH=);
2 2 3
128.43 (CAr—CH=C); 132.33 (CArH); 137.06 (CAr—CH=);
3
150.38 (CAr—NMe ); 186.39 (C=O).
2