Studies of 4H-3,1-benzoxazines. 14. Structure and some properties of 2-[2-hydroxyphenyl(naphthyl)]-1,2-dihydro-4H-3,1-benzoxazines

Article abstract of DOI:10.1007/s10593-006-0205-0

It has been shown that the condensation of tertiary aminophenylcarbinols with 2-hydroxybenz(naphth)aldehydes gives the corresponding 1,2- dihydrobenzoxazines and their structural Schiff base isomers. The reaction of 2-[2-hydroxyphenyl(naphthyl)]-1,2-dihyd

Full text of DOI:10.1007/s10593-006-0205-0

Chemistry of Heterocyclic Compounds, Vol. 42, No. 8, 2006
STUDIES OF 4H-3,1-BENZOXAZINES.
14*. STRUCTURE AND SOME PROPERTIES
OF 2-[2-HYDROXYPHENYL(NAPHTHYL)]-
1,2-DIHYDRO-4H-3,1-BENZOXAZINES
E. V. Gromachevskaya, T. P. Kosulina, and A. A. Borodavko
It has been shown that the condensation of tertiary aminophenylcarbinols with
2-hydroxybenz(naphth)aldehydes gives the corresponding 1,2-dihydrobenzoxazines and their structural
Schiff base isomers. The reaction of 2-[2-hydroxyphenyl(naphthyl)]-1,2-dihydro-4H-3,1-benzoxazines
with aliphatic aldehydes gives substituted 3,1-benzoxazino[1,2-c][1,3]benz(naphth)oxazines.
Keywords:
3,1-benzoxazino[1,2-c][1,3]benz(naphth)oxazines,
2-hydroxybenz(naphth)aldehydes,
1,2-dihydro-4H-3,1-benzoxazines, isomers, mass spectra.
The main method for preparing 1,2-dihydro-4H-3,1-benzoxazines is the condensation of o-aminobenzyl
alcohols with carbonyl compounds under acid catalysis conditions [2, 3]. Their structure was established by the
spectral methods [3, 4]. However, it has been shown that the heterocycle unsubstituted in the 4 position can exist
in tautomeric equilibrium with an open (azomethine) form [3]. This tendency is most clearly seen in compounds
in which the alternative unsaturated structure is stabilized by an intramolecular hydrogen bond [3, 5].
Extending our investigation in this area by treating the carbinols 1a-c with the salicylaldehydes 2a-d in
acetic acid medium we have obtained a series of 2,4,4-trisubstituted 1,2-dihydro-4H-3,1-benzoxazines 3a-f
(Scheme 1) and we have studied their properties. A similar reaction of the carbinols 1a,b with 3-hydroxy-2-
naphthaldehyde gave yellow-orange crystals of the naphthylbenzoxazines 4a,b (Table 1). The cyclic structure
for compounds 3a-f was confirmed by analysis of their IR, UV, and 1H NMR spectra (Table 2).
O
X
OH
CH
X
N
N
H
HO
H
O
X = H, Br
_______
* For Communication 13 see [1].
__________________________________________________________________________________________
Kuban State Technological University, Krasnodar 350072, Russia; e-mail: kosylina@rambler.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1230-1241, August, 2006. Original article
submitted April 22, 2004; revision submitted September 28, 2005.
1068
0009-3122/06/4208-1068©2006 Springer Science+Business Media, Inc.

1069

TABLE 1. Physicochemical Characteristics of Compounds 3a-i, 5a-j, 6a-d
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Rf
Yield,
%
mp, °С
(benzene)
C
H
N
3а
3b
3с
3d
C26H21NO2
82.53
82.32
73.85
73.58
68.33
68.27
62.21
62.15
5.31
5.54
4.55
4.72
4.42
4.38
3.72
3.78
3.92
3.69
6.35
6.60
3.10
3.06
5.49
5.58
160-170
155-158
146-148
191-193
0.35
0.30
0.80
0.65
75
72
65
65
С26Н20N2O4
С26H20BrNO2
С26H19BrN2O4
3е
3f
С18Н20N2O4
С16Н16N2O4
C25H11NO2
C17H21NO2
C15H17NO2
C27H21NO2
С30Н26N2O4
С27Н20N2O4
С33Н32N2O4
С28Н23NO2
С28Н22N2O4
С31Н29NO2
С19H20N2O4
С20Н22N2O4
С17Н16N2O4
С31Н23NO2
С23H23NO2
C32H25NO2
C37H35NO2
65.52
65.58
6.42
6.09
8.92
8.54
123-125
130-132
163-165
45-47
0.30
0.35
0.75
0.6
65
60
60
55
52
70
55
65
45
60
60
60
65
68
70
72
70
65
35
64.08
64.00
5.42
5.33
9.28
9.33
3g
3h
3i
81.78
81.74
5.59
5.72
3.68
3.81
75.32
75.28
7.61
7.75
5.05
5.17
74.18
74.07
6.83
6.99
5.59
5.76
109-110
215
0.45
0.59
0.70
0.60
0.75
0.73
0.40
0.57
0.70
0.55
0.65
0.48
0.52
5а
5b
5c
5d
5e
5f
82.42
82.86
5.62
5.37
3.20
3.58
75.74
75.31
74.55
74.31
5.31
5.44
4.31
4.58
5.52
5.86
6.15
6.42
170-172
228-230
200-201
200-205
218-220
172-173
123-124
140-142
135-137
250-252
102-105
236-237
198-201
76.48
74.15
6.34
6.15
5.12
5.38
82.51
82.96
5.83
5.68
3.21
3.46
74.42
74.67
4.65
4.89
6.53
6.22
5g
5h
5i
83.57
83.22
6.72
6.48
3.28
3.13
67.42
67.06
5.62
5.88
8.48
8.23
67.45
67.79
6.03
6.21
7.64
7.90
5j
65.32
65.38
5.16
5.12
8.91
8.97
6а
6b
6c
6d
84.72
84.35
5.44
5.21
3.41
3.17
80.21
80.80
6.82
6.66
4.11
4.06
84.58
84.39
5.22
5.49
3.35
3.07
0.68
(benzene + ether)
84.82
84.57
6.31
6.67
2.43
2.67
0.58
The IR spectra of these compounds show absorbance stretching bands for the N–H bonds at
3320-3350 cm-1 and broad OH absorption stretching bands in the region 3000-3600 cm-1 which point to the
presence of an intramolecular hydrogen bond [6]. In addition, the IR spectra of compounds 4a,b show both the
OH and NH group absorption bands at 3600-3030 cm-1 and also stretching bands for the azomethine fragment at
1630-1610 cm-1.
1070

TABLE 2. Spectroscopic Characteristics of Compounds 3a-i, 5a-j, 6a-d
IR spectrum,
Com-
ν, cm-1
1Н NMR spectrum (CDCl3)*, δ, ppm (J, Hz)
pound
(vaseline oil)
1
2
3
3а
3330 (NH);
4.40 (1H, br. s, NH); 5.60 (1H, s, H-a); 6.90 (8H, m, Нarom);
3200-3070 (OH) 7.27 (10Н, m, (С6Н5)2); 8.40 (1Н, br. s, ОН)
3b
3350 (NH);
3300-3100 (OH);
1520, 1325 (NO2)
4.45 (1H, br. s, NH); 5.60 (1H, s, H-a); 6.80 (5H, m, С6Н4 + Нγ);
7.32 (10Н, m, (С6Н5)2); 7.95 (1Н, s, Н-α); 8.15 (1Н, d, 3Jβγ=8.0, Н-β);
9.50 (1Н, br. s, ОН)
3с
3600-3200 (OH), 5.70 (1H, s, H-a); 6.30 (1H, s, NH); 6.90 (16H, m, Нarom);
3320 (NH) 7.75 (1H, s, H-a); 9.70 (1Н, s, ОН)
3600-3300 (OH), 5.80 (1H, s, H-a); 6.20 (1H, br. s, NH); 6.55 (1H, dd, H-7),
3d
3320 (NH);
6.62 (1Н, d, Н-8), 6.75 (1Н, d, Н-5), 7.00 (1Н, dd, Н-6),
3
1520, 1350 (NO2) J8,7 = 7.7; 3J7,6 = 6.5; 3J5,6 = 7.7; 7.30 (10Н, m, (С6Н5)2);
8.15 and 8.17 (2Н, ss, Н-α + Н-β); 10.55 (1Н, br. s, ОН)
3е
3340 (NH);]
0.55 and 1.25 (6H, two t, (СН3)2), 1.60, 1.80, 2.15 and 2.25 (4H, four q,
3250-3300 (OH); (СН2)2), 3JCH CH = 7.0; 4.52 (1H, br. s, NH); 5.45 (1Н, s, Н-а);
2
3
7.10 (5Н, m, (С6Н4) + Н-γ); 8.15 (1Н, d, 3Jβγ = 7.7; Н-β);
8.25 (1Н, s, Н-α); 9.20 (1Н, br. s, ОН)
1510, 1330 (NO2)
3f
3400-3100 (OH); 1.55 and 1.62 (6H, two s, (СН3)2); 5.80 (1H, br. s, NH);
3300 (NH);
1530, 1310 (NO2)
5.90 (1Н, s, Н-а); 6.80 (5Н, m, (С6Н4) + Н-γ);
8.00 (1Н, d, 3Jβγ = 7.5, Н-β); 8.35 (1Н, s, Н-α); 10.85 (1Н, br. s, ОН)
3g
3h
3450 (NH)
2.25 (3Н, s, СН3); 4.35 (1Н, d, NH), 5.45 (1Н, d, Н-а), 3JНαNH = 5.0;
5.85 (1Н, d, Н4fur), 6.30 (1Н, d, Н3fur), 3J3,4 = 3.0; 6.85 (4Н, m, С6Н4);
7.25 (10Н, m, (С6Н5)2)
3400 (NH)
0.6 and 1.0 (6H, two t, (СН3)2), 1.60, 1.80, 1.92 and 2.15 (4H, four q,
(СН2)2), 3JСН СН = 7.5; 2.35 (3Н, s, СН3); 5.50 (1Н, s, Н-а);
2
3
5.85 (1Н, br. s, NH); 6.00 (1Н, d, Н4fur), 6.35 (1Н, d, Н3fur) 3J3,4 = 3.0;
6.80 (4Н, m, С6Н4)
3i
3360 (NH)
1.50 and 1.60 (6H, two s, (СН3)2); 2.35 (3Н, s, СН3); 5.55 (1Н, s, Н-а);
5.90 (1Н, br. s, NH); 6.00 (1Н, d, Н4fur), 6.35 (1Н, d, Н3fur), 3J3,4 = 3.0;
6.80 (4Н, m, С6Н4)
5.15 and 5.25 (2Н, two d, 2Jbс = 8.0, Нb+Нс); 5.35 (1Н, s, На);
5а
—
7.20 (18Н, m, Нarom
)
0.90 (3Н, t, 3JCH CH = 6.5, СН3); 1.51 (4Н, m, (СН2)2); 5.40 (1H, s, Ha);
5b
1510, 1330 (NO2)
2
3
5.72 (1H, t, 3JCHCH = 5.0, Нb); 7.10 (15Н, m, С6Н4+(С6Н5)2+Нγ),
2
8.05 (1H, s, Нα); 8.20 (1Н, d, 3Jβγ= 7.8, Нβ)
5c
1520, 1340 (NO2) 5.35 and 5.45 ( 2Н, two d, 2Jbc = 7.5, Нb+Нс); 5.55 (1Н, s, На);
7.25 (15Н, m, С6Н4+(С6Н5)2+Нγ); 7.90 (1Н, s, Нα); 8.20 (1Н, d,
3Jβγ = 8.0, Нβ)
0.85 (3Н, t, 3J CH CH = 7.0, СН3); 1.65 (10Н, m, (СН2)5);
5d
1520, 1330 (NO2)
2
3
5.30 (1Н, s, На); 5.95 (1Н, t, 3J CHCH = 5.5, Нb); 7.25 (15Н, m,
2
С6Н4+(С6Н5)2+Нγ); 7.85 (1Н, s, Нα); 8.20 (1Н, d, 3Jβγ= 7.5, Нβ)
1.62 (3Н, d, СН3), 5.35 (1Н, q, Нb), 3JCHCH = 6.0; 5.50 (1Н, s, На);
5e
5f
—
1510, 1350 (NO2)
—
3
7.25 (18Н, m, Нarom
)
1.57 (3Н, d, СН3), 5.45 (1Н, q, Нb), 3JCHCH = 6.0; 5.75 (1Н, s, На); 7.15
3
(15Н, m, С6Н4+(С6Н5)2+Нγ); 7.9 (1Н, s, Нα); 8.2 (1Н, d, 3Jβγ = 7.6, Нβ)
1.10 (6Н, d, 3J CHCH = 6.9, (СН3)2); 1.57 (2Н, m, СН2);
5g
3
2.55 (1Н, m, СН); 5.40 (1Н, s, На); 5.71 (1Н, t, 3J CHCH = 5.0, Нb);
2
7.05 (18Н, m, Нarom
)
5h
5i
1510, 1330 (NO2) 0.55 and 1.20 (6Н, two t, (СН3)2), 1.65, 1.82, 2.15 and 2.35 (4Н, four q,
(СН2)2), 3J CH CH = 7.0; 5.05 (2Н, s, Нb+Нс); 5.45 (1Н, s, На);
2
3
7.20 (5Н, m, С6Н4+Нγ); 8.15 (1Н, d, 3Jβγ= 7.8, Нβ); 8.25 (1Н, s, Нα)
1520, 1330 (NO2) 0.58 and 1.18 (6Н, two t, (СН3)2), 1.55 (3Н, d, СН3), 1.65, 1.85,
2.15 and 2.28 (4Н, four q, (СН2)2), 3JCH 3 = 7.0, 5.30 (1Н, q,
CH
2
3J CHCH = 5.5, Нb); 5.45 (1Н, s, На); 7.15 (5Н, m, С6Н4+Нγ);
3
8.15 (1Н, d, 3Jβγ = 7.8, Нβ); 8.20 (1Н, s, Нα)
1071

TABLE 2 (continued)
1
2
3
5j
1520, 1340 (NO2) 1.50 and 1.65 (6Н, two s, (СН3)2); 5.25 and 5.35 (2Н, two s, Hb+Hc);
5.50 (1Н, s, На); 7.10 (5Н, m, С6Н4+Нγ); 8.10 (1Н, d, 3Jβγ = 7.7, Нβ);
8.35 (1Н, s, Нα)
3030, 1610, 1590; 5.10 (1Н, d, Нb), 5.42 (1Н, d, Нс), 2Jbc = 8.0; 5.65 (1Н, s, На);
6а
1080, 1040
7.35 (20Н, m, Нarom
)
0.42 (3Н, t, СН3(а)), 1.25 (3Н, t, СН3(е)), 3J CH CH = 7.1; 2.08 (4Н, m,
6b
3030, 1610, 1580;
1070, 1030
2
3
(СН2)2); 4.95 (1Н, d, Нb), 5.20 (1Н, d, Нс), 2Jbc = 7.0; 5.90 (1Н, s, На);
7.50 (10Н, m, Нarom
1.68 (3Н, m, СН3); 5.80 (1Н, s, На); 6.35 (1Н, q, 3J CHCH = 6.0, Нb);
)
6c
3030, 1610, 1580;
1080, 1060
3
7.10 (20Н, m, Нarom
)
0.80 (3H, t, 3J CH CH = 6.0, CH3); 1.22 (10H, m, (CH2)5);
6d
30.30, 1590,
2
3
1580, 1050, 1100 5.85 (1H, t, 3J CHCH = 7.0, Hb); 7.05 (1H, s, Ha); 7.45 (20H, m, Harom
)
2
_______
* 1H NMR spectrum of compounds 5c,d recorded in DMSO-d6.
The UV spectra of compound 3a show the presence of two absorption maxima at 242 and 277 nm which
are typical of a benzoxazine structure [2]. However, the UV spectra of compounds 4a,b show both the short
wavelength maximum absorptions at 231 and 263 nm (structure A) and also two long wavelength maxima at 317
and 450 nm which are evidently typical of a longer chain π-π* and p-π* conjugated azomethine system (B)
which points to the presence of these compounds as a tautomeric equilibrium of the cyclic (A) and linear (B)
forms in the alcohol solvents [6].
1
The H NMR spectra of compounds 3a-f show broad singlets for the phenolic groups at 8.4-10.8, NH
protons at 4.4-6.3, and the Ha proton singlets at 5.4-5.9 ppm and this confirms the cyclic structure of the
1
benzoxazines. At the same time, the H NMR spectra of compounds 4a,b show signals for both the protons of
the cyclic form A (Ha at 4.2-4.8, phenolic OH at 8.81-9.25, and NH protons at 8.08-8.35 ppm) and also for the
linear (azomethine) form B (CH=N at 8.55, OHphen 9.68-9.80, and OHalc 6.32-6.42 ppm). Comparison of the
integrated intensities of these signals shows that the ratio of forms A to B is 1:4.
Analysis of the mass spectra of compounds 3a-d,f and 4a,b (Table 3) shows the presence of the sample
molecular ion peaks [M]+. The fragmentation of M+ for the dihydrobenzoxazines 3a-d,f (Scheme 2) is
characterized by the fission of a 2-hydroxybenzaldehyde [retrodiene decomposition (RDD)] or of an aromatic
aldehyde radical (RDD + H) to give ions Φ2 and Φ4 which, in turn, lose an atom or molecule of hydrogen Φ3
(RDD – H process). The ions Φ2-Φ4 are typical of the mass spectroscopic decomposition of M+ in 2,4-substituted
1,2-dihydro-4H-3,1-benzoxazines [4].
An additional fragmentation event for the molecular ion in these compounds is the loss of water to form
the ion Φ1 which is specific to the decomposition of saturated alcohols [7] and can point to the presence of the
hydroxyl group in the structures studied. Hence on the basis of the spectroscopic analytical data (see Tables 2
and 3) we have shown that the products 3a-f are substituted dihydrobenzoxazines and compounds 4a,b are a
mixture of the structural isomers A and B (see Scheme 1) with the latter predominating.
The dihydrobenzoxazines 3a-d and 4a,b (form A) have two potential reaction centers able to interact
with carbonyl compounds, i.e. the amino NH and phenol groups. The reactivity of such systems in similar
reactions has been studied before for dihydroquinazolinones [8] which have a hydroxyl group in the β-position
of an aryl substituent placed at position 2 of the heterocycle. Such a reaction for dihydrobenzoxazines has been
little studied and only isolated examples have been reported [5, 9].
We have studied the reactions of compounds 3a,b,e,f and 4a,b with aliphatic, aromatic, and furan
aldehydes.
1072

1073

1074

It was found that the dihydrobenzoxazines 3a,b,e,f and 4a,b react with aliphatic aldehydes in acetic acid
[2] to give 45-70% yields of the corresponding tetra(penta)cyclic structures 3,1-benzoxazino[1,2-c][1,3]-
benzoxazines 5a-j and 3,1-benzoxazino[1,2-c][1,3]naphthoxazines 6a-d. The preparation of the latter is possible
in the case of a shift of the A to B tautomeric equilibrium to the side of the cyclic form A which takes part in the
reaction (see Scheme 1 and Tables 1 and 2).
The yields and ease of carrying out the reactions reported depend on the size of the radical of the
attacking aliphatic aldehyde. With formaldehyde the reaction occurs at room temperature. The reaction of
compound 3b and the mixture of isomers 4a with heptanal occurs at a higher temperature (34-36°C) for 3 h to
give the products 5d and 6d in 45 and 35% yields respectively (Table 1). Monitoring of the reaction was carried
out by TLC.
1
The H NMR spectra of compounds 5a,c and 6a,b show Hb and Hc geminal proton signals as two
doublets and in compounds 5f,i, 6c and 5d,g, 6d the Ha signal appears as quadruplets and triplets respectively
(Table 2) thus confirming the structure of the heterocycle. In the 1H NMR spectra of compounds 5h,j the doublet
splitting of the Hb and Hc protons is absent but the tetracyclic structure of these compounds is confirmed by mass
spectroscopic data with the fragmentation of the molecular ions [M]+ following the overall scheme (Table 3 and
Scheme 3). Initial mass spectroscopic decomposition of M+ in compounds 5a,d,h,j, 6b occurs with fission of 2-
hydroxybenz(naphth)oyl (RDD + H process [4]) and aliphatic R and R3 radicals to give the cations Φ4, Φ7, and
Φ9 respectively.
TABLE 3. Mass Spectra of Compounds 3a-d,f, 4a,b, 5a,d,h,j, 6b
Com-
pound*
m/z (Irel, %)*2
3a
3b
3c
379 (12), 361 (23), 258 (30), 256 (100), 255 (16), 254 (22), 180 (95), 165 (30),
152 (22), 121 (30), 105 (26), 77 (38)
424 (25), 406 (15), 258 (23), 256 (100), 255 (19), 254 (20), 180 (45), 165 (18),
105 (19), 77 (30)
457 (20), 439 (90), 272 (6), 258 (50), 256 (100), 255 (31), 254 (38), 180 (35),
165 (15), 152 (10), 105 (12), 77 (18)
3d
3f
502 (10), 484 (8), 258 (10), 256 (100), 254 (15), 180 (22), 165 (5), 105 (8), 77 (5)
300 (28), 285 (18), 282 (5), 267 (9), 144 (30), 134 (60), 133 (100), 132 (65),
118 (28), 106 (10), 91 (31), 77 (16)
4а
4b
5а
429 (28), 411 (95), 272 (18), 258 (51), 256 (100), 255 (81), 254 (38), 180 (60),
172 (13), 165 (42), 105 (30), 77 (71)
333 (29), 315 (5), 304 (35), 286 (13), 162 (36), 160 (100), 159 (40), 144 (61),
132 (20), 115 (40), 91 (15), 77 (20)
391 (25), 313 (10), 270 (100), 194 (5), 180 (9), 165 (22), 152 (8), 132 (3), 121 (8),
105 (4), 91 (10), 77 (12)
5d
5h
520 (52), 435 (80), 354 (100), 270 (19), 254 (3), 206 (4), 180 (3), 165 (22), 91 (3), 77 (4)
340 (18), 311 (100), 265 (6), 174 (12), 144 (10), 132 (15), 130 (15), 118 (6), 91 (8),
77 (10)
5j
312 (15), 297 (12), 146 (100), 131 (20), 130 (30), 118 (10), 117 (13), 106 (6), 91 (18),
77 (16)
6b
345 (15), 316 (48), 174 (100), 144 (39), 132 (21), 130 (40), 118 (27), 115 (33),
91 (19), 77 (35)
_______
* Compound 3g M+ = 367; compound 3h M+ = 271.
*2 M+ peaks and ion intensities are given. For compounds 3c,d the m/z
values are calculated for the lighter halogen isotope.
1075

According to the mechanism of interaction of aminoalcohols with aldehydes [10, 11] the first stage in
the formation of the 3,1-benzoxazino[1,2-c][1,3]benz(naphth)oxazines 5a-j, 6a-d is likely a nucleophilic
addition of the amino group of the dihydrobenz(naphth)oxazines 3a-d, 4a,b to the carbonyl carbon to form the
intermediate C (see Scheme 1). Further reaction can then occur by two routes which are determined by the
structure both of the benzoxazines and the aldehyde. Formation of an additional six-membered heterocycle and
thus the structure 5a-j, 6a-d is characteristic only of aliphatic aldehydes. On changing to more bulky or aromatic
aldehydes (chloral, furfural, nitrofurfural, or methylfurfural) exchange in the starting substrate of a
2-hydroxyphenyl(naphthyl) or 2-hydroxy-5-nitrophenyl radical for the attacking aldehyde occurs. The
parameters for the dihydrobenzoxazines 3j-l formed agree with those given in [4]. The data for the
dihydrobenzoxazines 3a-i are recorded for the first time by us and are given in the Experimental and in Tables 1
and 2.
The dihydrobenzoxazines 3a-d do not react with ketones (acetone, methylethyl ketone), probably as a
result of steric hindrance.
EXPERIMENTAL
IR spectra were taken on Specord-71 and Infralum FT-02 instruments using vaseline oil or in CCl4 and
1H NMR spectra on Tesla BS-467 (60 MHz), Varian VXR-400 (400 MHz), or Bruker DRX 500 (500 MHz)
instruments using TMS as internal standard. Mass spectra were obtained on a Varian MAT CH-6 instrument
with direct introduction of the sample into the ionization chamber at a temperature of 50-180°C and ionization
energy of 70 eV. Electronic spectra were recorded on a Specord UV-vis spectrometer using ethanol. TLC was
carried out on Silufol UV-254 plates using the system benzene–ether (4:1) and were revealed using iodine vapor.
o-Aminophenylcarbinols 1a-c were prepared by reaction of methyl anthranilate with the corresponding
alkylmagnesium halide [2]. Carbinol 1b. Yield 76%; mp 59-60°C. Found, %: C 73.9; H 9.20; N 7.6. C11H17NO.
Calculated, %: C 74.2; H 9.5; N 7.8.
Dihydrobenzoxazines 3a-f were prepared by method [2] in acetic acid at room temperature.
Mixture of 2-(2-Hydroxynaphthyl)-4,4-diphenyl-1,2-dihydro-4H-3,1-benzoxazine (4a, A) and o-(3-
Hydroxy-2-naphthylideneaminophenyl)diphenylmethanol (4a, B). 3-Hydroxy-2-naphthaldehyde (1.1 g, 6.4
mmol) was added to a vigorously stirred solution of the carbinol 1a (1.76 g, 6.4 mmol) in acetic acid (5-7 ml)
and the mixture was heated for 2 h on a water bath at 40-50°C. The product was cooled and the precipitate
formed was filtered off and washed with a small amount of acetic acid and water. Yield 72%, mp 160-164°C. IR
spectrum (thin layer), ν, cm-1: 3600, 3540, 3200, 3030, 1610, 1590. UV spectrum (EtOH), λmax, nm (log ε): 231
1
(4.65), 263 (4.6), 317 (3.99), 450 (4.01). H NMR spectrum (DMSO-d6), δ, ppm: A 8.81 (1H, s, OHPh); 8.08
(1H, s, NH); 6.5-7.8 (20H, m, Harom); 4.2 (1H, s, Ha). B 9.68 (1H, s, OHPh); 8.55 (1H, s, CH=N); 6.5-7.8 (20H,
m, Harom) and 6.42 (1H, s, OHalc). Found, %: C 84.72; H 5.44; N 3.41. C31H23NO2. Calculated, %: C 84.35;
H 5.21; N 3.17. M+ 429.
Mixture of 4,4-Diethyl-2-(2-hydroxynaphthyl)-1,2-dihydro-4H-3,1-benzoxazine (4b, A) and
o-(3-Hydroxy-2-naphthylideneaminophenyl)diethylmethanol (4b, B) was obtained similarly. Yield 70%;
1
mp 98-103°C. IR spectrum (thin layer), ν, cm-1: 3400, 3290, 3100, 3030, 1630, 1590, 1580. H NMR spectrum
(DMSO-d6), δ, ppm: A 9.25 (1H, s, OHPh); 8.35 (1H, s, NH); 6.7-7.8 (10H, m, Harom); 4.8 (1H, s, Ha); 2.25 (4H,
m, 2CH2) and 0.95 (6H, t, 2CH3). B 9.80 (1H, s, OHPh); 8.55 (1H, s, CH=N); 6.7-7.8 (10H, m, Harom); 6.32 (1H,
s, OHalc); 1.75 (4H, m, 2CH2); 0.75 (6H, t, 2CH3). Found, %: C 80.21; H 6.82; N 4.11. C23H23NO2.
Calculated, %: C 80.80; H 6.66; N 4.06. M+ 333.
2-(5-Methylfur-2-yl)-4,4-diphenyl-1,2-dihydro-4H-3,1-benzoxazine (3g). A.
A
solution of
5-methylfurfural (0.09 g, 0.84 mmol) in acetic acid (2-3 ml) was added in small portions with vigorous stirring
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to a solution of the benzoxazine 3a (0.32 g, 0.84 mmol) in acetic acid (5 ml) at room temperature and stirred for
30-40 min. The precipitated crystals were filtered off, recrystallized from alcohol, and dried. Yield 0.18 g (60%).
B. A solution of 5-methylfurfural (0.09 g, 0.84 mmol) in acetic acid (3 ml) was added in small portions
to a solution of the dihydrobenzoxazine 4a (a mixture of A and B isomers) (0.38 g, 0.84 mmol) in acetic acid
(5 ml). The mixture was heated on a water bath at 40-45°C for 2-3 h until the yellow color had disappeared. It
was then cooled, recrystallized from alcohol, and dried. Yield 0.14 g (45%).
4,4-Diethyl(methyl)-2-(5-methylfur-2-yl)-1,2-dihydro-4H-3,1-benzoxazines 3h,i (see Table 1) were
prepared similarly from the dihydrobenzoxazines 3e,f using method A.
Dihydrobenzoxazines 3j-l were prepared by methods A and B.
4,4-Diphenyl-3,1-benzoxazino[1,2-c][1,3]benzoxazine (5a). A mixture of the dihydrobenzoxazine 3a
(0.95 g, 2.5 mmol) and formalin (0.2 ml, containing 2.5 mmole formaldehyde) in acetic acid (10 ml) was stirred
at room temperature for 40 min. The original precipitate of the dihydrobenzoxazine 3a disappeared and was
replaced by a new precipitate which was filtered off, washed with aqueous alcohol (3:1), dried, and
recrystallized from toluene. Yield 0.69g (70%).
Compounds 5b-j and 6a-c were prepared similarly using the dihydrobenzoxazines 3a,b,e,f, 4a,b and
the corresponding aldehyde.
11-Hexyl-15-nitro-4,4-diphenyl-3,1-benzoxazino[1,2-c][1,3]benzoxazine (5d). A mixture of the
dihydrobenzoxazine 3b (1.06 g, 2.5 mmol) and heptanal (0.28 g, 2.5 mmol) in acetic acid (10 ml) was stirred for
3 h at 35-40°C. The precipitate formed was filtered off, washed with aqueous alcohol (3:1), dried, and
recrystallized from toluene. Yield 0.58 g (45%).
11-Hexyl-4,4-diphenyl-3,1-benzoxazino[1,2-c][1,3]naphthoxazine (6d) was prepared similarly from
4a and heptanal.
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