Transformations of acylation products of functionally 4-substituted 2-alkyl(aryl)-5-hydrazino-1,3-oxazoles into 1,3,4-oxadiazole derivatives

Article abstract of DOI:10.1007/s11176-005-0244-8

Acylation products of 2-aryl-5-hydrazino-4-X-1,3-oxazoles [X = C(O)OAlk, P(O)(OAlk)²], when heated in acetic acid or ethanol, undergo recyclization and transform into the derivatives of 1,3,4-oxadiazol-2-ylglycine or its phosphonyl analog. A si

Full text of DOI:10.1007/s11176-005-0244-8

Russian Journal of General Chemistry, Vol. 75, No. 3, 2005, pp. 425 431. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005,
pp. 461 467.
Original Russian Text Copyright
2005 by Golovchenko, Pil’o, Brovarets, Chernega, Drach.
Transformations of Acylation Products of Functionally
4-Substituted 2-Alkyl(aryl)-5-hydrazino-1,3-oxazoles
into 1,3,4-Oxadiazole Derivatives
A. V. Golovchenko, S. G. Pil’o, V. S. Brovarets, A. N. Chernega, and B. S. Drach
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received August 6, 2003
Abstract Acylation products of 2-aryl-5-hydrazino-4-X-1,3-oxazoles [X = C(O)OAlk, P(O)(OAlk)2], when
heated in acetic acid or ethanol, undergo recyclization and transform into the derivatives of 1,3,4-oxadiazol-2-
ylglycine or its phosphonyl analog. A similar rearrangement also occurs in the reactions of 2-alkyl(aryl)-5-
hydrazino-1,3-oxazole-4-carbonitriles with carboxylic acid chlorides in pyridine, but it is accompanied by
additional cyclization involving the amide residue and nitrile group, yielding 2-(5-amino-1,3-oxazol-4-yl)-
1,3,4-oxadiazole derivatives.
A systematic study of the reactions of , -disubsti-
tuted enamides I III with hydrazine hydrate, initiated
recently [1 3] and continued in this work, showed that
the possible applications of this polycondensation are
fairly wide, and it is indispensable for preparative
synthesis of 5-hydrazino-1,3-oxazole derivatives IV
was unambiguously proved by spectral and chemical
methods [2]. The acylation pathway of substrates VI
changes if the acylation with carboxylic acid chlorides
is performed in pyridine. The -acylation products IX
formed in the first step are difficult to isolate pure,
because they readily undergo further transformations
VI containing in 4-position various electron-withdraw- (see scheme). However, we were able to isolate one of
ing groups: C(O)OAlk, P(O)(OAlk)2, and C N. The
1H NMR and IR spectra of these products are consist-
ent with their suggested structures (Table 1). Trans-
these compounds (X = CN, R1 = R2 = 4-CH3C6H4)
and to record its H NMR spectrum. The spectrum
contained two broadened singlets at 10.43 and
10.93 ppm, assignable to two different N H pro-
tons in the HtNHNHCO group.
1
formations I
IV, II
V, and III
VI are similar
to the extensively studied cyclocondensations of en-
amides I III with primary and secondary amines (see
references in [4]). Therefore, there is no doubt that
compounds IV VI are, indeed, the 5-hydrazino-1,3-
oxazole derivatives differently reacting with carboxyl-
ic acid chlorides in the presence of bases. The reaction
pathway essentially depends on the structure of elec-
tron-withdrawing substituents in 4-position of the
heteroring and on the acylation conditions. In particu-
lar, acylation of the hydrazino group in alkyl esters of
2-aryl-5-hydrazino-1,3-oxazole-4-carboxylic acids IV
and their phosphonyl analogs V in acetonitrile in the
presence of an equimolar amount of triethylamine
mainly occurs at the nitrogen atom more remote from
the oxazole ring. The reaction yields -acylation prod-
ucts VII and VIII containing the HtNHNHCO frag-
The structural similarity of -acylation products
VII IX was proved not only by spectroscopy, but
also by the fact that, in contrast to the isomeric
-acylation products, compounds VII IX after
approoriate treatment transformed into 1,3,4-oxa-
diazole derivatives. In particular, substrates VII
and VIII, when heated in acetic acid or ethanol,
recyclize (see scheme) into the corresponding de-
rivatives of 1,3,4-oxadiazol-2-ylglycine (X) or its
phosphonyl analog (XI) (Table 2). The presence of
the CHNH and PCHNH groups in X and XI is
1
confirmed by the H NMR spectra in the regions
of 6.1 6.4 and 9.6 9.8 ppm (Table 1). The signals
were reliably assigned by comparison of the 1H
NMR spectra of compounds X and those of the
related 1,3,4-oxadiazole derivatives C (see below)
whose structure was proved by single crystal X-ray
diffraction [2].
1
ment, as indicated by the H NMR spectra (Table 1).
At the same time, 2-aryl-5-hydrazino-1,3-oxazole-
4-carbonitriles VI structurally related to IV and V
react with carboxylic acid chlorides in the presence of
triethylamine quite differently, yielding mainly the
-acylation products HtN(COR2)NH2 whose structure
It should be noted that compounds VII do not
transform into X even upon prolonged heating when
acetic acid or ethanol as solvent is replaced by
1070-3632/05/7503-0425 2005 Pleiades Publishing, Inc.

426
GOLOVCHENKO et al.
X
X
N
HN
H2N NH2 H2O (excess)
R1
Cl
R1
NH
O Cl
O
NH2
Ia Ic, IIa IIc, IIIa IIIc
IVa IVc, Va Vc, VIa VIc
R2C(O)Cl, :B
X
X
X
HN
N
N
R1
R1
R1
N
N
NH
NH
HY
O Y
O
O
NH
NH
O
O
O
R2
R2
R2
VIIa VIIf, VIIIa VIIId,
IXa IXi
A
B
X = C(O)OAlk
X = P(O)(OAlk)2
H
H
N
N N
R2
O
N N
R2
O
R1
R1
N
P
O
O
OAlk
O
O
OAlk
X = CN
OAlk
XIa XId
Xa Xf
H
N N
O
N N
, :B
R2
R2
R1
N
N
O
NH2
R1
O
C
N
O
XIIa XIIi
XIIIa XIIIi
I, II, IV, V, R1 = C6H5, Alk = CH3 (a); R1 = 4-CH3C6H4, Alk = CH3 (b); R1 = C6H5, Alk = C2H5 (c). III, VI, R1 = C6H5
(a), 4-CH3C6H4 (b), CH3 (c). VII, X, R1 = R2 = C6H5, Alk = CH3 (a); R1 = 4-CH3C6H4, Alk = CH3, R2 = C6H5 (b);
R1 = R2 = C6H5, Alk = C2H5 (c); R1 = C6H5, Alk = CH3, R2 = 4-CH3C6H4 (d); R1 = C6H5, Alk = C2H5, R2 =
4-CH3C6H4 (e); R1 = R2 = 4-CH3C6H4, Alk = CH3 (f). VIII, XI, R1 = R2 = C6H5, Alk = CH3 (a); R1 = R2 = 4-CH3C6H4,
Alk = CH3 (b); R1 = C6H5, Alk = C2H5, R2 = 4-CH3C6H4 (c); R1 = C6H5, Alk = CH3, R2 = 4-CH3C6H4 (d). IX, XII,
XIII, R1 = R2 = C6H5 (a); R1 = 4-CH3C6H4, R2 = C6H5 (b); R1 = CH3, R2 = C6H5 (c); R1 = C6H5, R2 = 4-CH3C6H4 (d);
R1 = C6H5; R2 = CH3 (e); R1 = R2 = 4-CH3C6H4 (f); R1 = 4-CH3C6H4, R2 = CH3 (g); R1 = CH3, R2 = 4-CH3C6H4 (h);
R1 = R2 = CH3 (i). X = AlkOC(O) (I, IV, VII), (AlkO)2P(O) (II, V, VIII), N C (III, VI, IX).
zation B
X or XI resembles the previously found
H
N
N N
transformation of N,N -diacyl derivatives of hydra-
zine into 1,3,4-oxadiazole derivatives [5]. Recycliza-
tion IX
R
CH3
O
NH2
B
XII occurs similarly but is compli-
O
O
cated by additional intramolecular reaction of the
cyano group and amide residue. Cyclization XII
XIII is a particular case of well-known transforma-
tions of some -acylamino nitriles into 5-amino-
1,3-oxazole derivatives, which are formed in the
presence of bases or acids [6]. The disappearance
of the C N bond and formation of a primary
amino group in the series of successive reactions
C
dioxane. This fact suggests important role not only
of prototropic tautomers A, but also of acyclic
products B formed by cleavage of 5-imino-2-oxazo-
line moiety with ethanol, acetic acid, or other com-
pounds with a labile hydrogen atom. Further cycli-
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TRANSFORMATIONS OF ACYLATION PRODUCTS
427
Table 1. Spectroscopic data for compounds IV, V, VII XI, and XIII
1
IR spectrum, , cm
1H NMR spectrum, , ppm (J, Hz)
IVa
IVb
IVc
1680 (C=O), 3360 (NH)
1680 (OC=O), 3340 (NH)
1660 (OC=O), 3220 (NH)
1240(P=O), 3280 (NH)
3.75 s (3H, OCH3), 4.70 br.s (2H, NH2), 7.40 7.88 m (5H, C6H5),
8.09 br.s (1H, NH)
2.34 s (3H, CH3), 3.71 s (3H, OCH3), 4.80 br.s (2H, NH2), 7.31 7.73 m
(4H, C6H4), 8.27 br.s (1H, NH)
1.31 t (3H, CH3), 4.22 q (2H, OCH2), 4.74 br.s (2H, NH2), 7.40 7.95 m
(5H, C6H5), 8.09 br.s (1H, NH)
3
Va
3.69 d (6H, 2OCH3, JHP 12.1), 4.80 br.s (2H, NH2), 7.48 7.84 m (6H,
NH)
VIIa
VIIc
VIId
VIIe
VIIf
1640(NC=O), 1680(OC=O), 3480(NH) 3.82 s (3H, OCH3), 7.43 7.95 m (10H, 2C6H5), 9.28 s (1H, NH),
10.87 s (1H, NH)
1645(NC=O), 1680(OC=O), 3370(NH) 1.36 t (3H, CH3), 7.32 q (2H, OCH2), 7.43 7.96 m (10H, 2C6H5), 9.17 s
(1H, NH), 10.86 s (1H, NH)
1640 (NC=O), 1670 (OC=O), 3390 (NH) 2.41 s (3H, CH3), 3.81 s (3H, OCH3), 7.33 7.86 m (9H, C6H5, C6H4),
9.21 s (1H, NH), 10.77 s (1H, NH)
1620 (NC=O), 1680 (OC=O), 3420 (NH) 1.35 t (3H, CH3), 2.41 s (3H, CH3), 4.32 q (2H, OCH2), 7.36 7.93 m
(9H, C6H5, C6H4), 9.10 s (1H, NH), 10.76 s (1H, NH)
1630 (NC=O), 1680 (OC=O), 3410 (NH)
VIIIb 1220 (P=O), 1680 (NC=O), 3220 (NH) 2.35 s (3H, CH3), 2.40 s (3H, CH3), 3.72 m (6H, 2OCH3), 7.23 7.83 m
(8H, 2C6H4), 8.43 s (1H, NH), 10.64 s (1H, NH)
IXf
Xa
Xb
Xc
1660 (NC=O), 2200 (C N), 3200 (NH) 2.37 s (6H, 2CH3), 7.32 7.81 m (8H, 2C6H4), 10.43 br.s (1H, NH),
10.93 br.s (1H, NH)
3
1650 (NC=O), 1750 (OC=O), 3250 (NH) 3.81 s (3H, OCH3), 6.20 d (1H, CH, JHH 7.5), 7.46 8.07 m (10H,
3
2C6H5), 9.69 d (1H, NH, JHH 7.5)
1650 (NC=O), 1770 (OC=O), 3225 (NH) 2.39 s (3H, CH3), 3.81 s (3H, OCH3), 6.15 d (1H, CH, 3JHH 7.5), 7.26
3
8.03 m (9H, C6H5), 9.54 d (1H, NH, JHH 7.5)
1645 (NC=O), 1745 (OC=O), 3270 (NH) 1.28 s (3H, CH3), 4.27 q (2H, OCH2), 6.13 d (1H, CH, 3JHH 7.5), 7.46
3
8.09 m (10H, 2C6H5), 9.65 d (1H, NH, JHH 7.5)
Xd
Xe
1650 (NC=O), 1750 (OC=O), 3260 (NH) 2.42 s (3H, CH3), 3.81 s (3H, OCH3), 6.18 d (1H, CH3, 3JHH 7.5), 7.38
3
7.95 m (9H, C6H5, C6H4), 9.64 d (1H, NH, JHH 7.5)
1645 (NC=O), 1750 (OC=O), 3250 (NH) 1.27 t (3H, CH3), 2.42 s (3H, CH3), 4.26 q (2H, OCH2), 6.10 d (1H, CH,
3
3JHH 7.5), 7.38 7.97 m (9H, C6H5, C6H4), 9.62 d (1H, NH, JHH 7.5)
Xf
1645 (NC=O), 1760 (OC=O), 3250 (NH) 2.42 s (6H, 2CH3), 3.80 s (3H, OCH3), 6.13 d (1H, CH, 3JHH 7.5), 7.26
3
7.91 m (8H, 2C6H4), 6.34 d (1H, NH, JHH 7.5)
3
2
XIa
XIb
1240 (P=O), 1680 (OC=O), 3230 (NH) 3.86 m (6H, 2OCH3), 6.70 d.d (1H, CH, JHH 8.7, JHP 21.6), 7.45
3
8.04 m (10H, 2C6H5), 9.59 d (1H, NH, JHH 8.7)
1240 (P=O), 1670 (OC=O), 3230 (NH) 2.41 s (3H, CH3), 2.42 s (3H, CH3), 3.84 m (6H, 2OCH3), 6.21 d.d (1H,
NCHP, 3JHH 8.7, 2JHP 21.6), 7.25 7.91 m (8H, 2C6H4), 9.43 d (1H, NH,
3JHH 8.7)
XIc
XId
1240 (P=O), 1680 (OC=O), 3220 (NH) 1.27 m (6H, 2CH3), 2.42 s (3H, CH3), 4.18 m (4H, 2CH2), 6.09 d.d (1H,
NCHP, 3JHH 8.6, 2JHP 21.8), 7.38 7.96 m (9H, C6H4, C6H5), 9.57 d (1H,
3
NH, JHH 8.6)
1235 (P=O), 1685 (OC=O), 3220 (NH) 2.42 s (3H, CH3), 3.84 m (6H, 2OCH3), 6.21 d.d (1H, NCHP, 3JHH 8.7,
3
2JHP 21.6), 7.37 7.97 m (9H, C6H5, C6H4), 9.53 d (1H, NH, JHH 8.7)
XIIIa 3280, 3410 (NH2)
XIIIb 3280, 3410 (NH2)
XIIIc 3290, 3380 (NH2)
XIIIda 3280, 3420 (NH2)
7.43 8.14 m (12H, 2C6H5, NH2)
2.36 s (3H, CH3), 7.34 8.10 m (11H, C6H5, C6H4, NH2)
2.33 s (3H, CH3), 7.14 br.s (2H, NH2), 7.59 8.07 m (5H, C6H5)
2.40 s (3H, CH3), 7.40 8.01 m (11H, C6H5, C6H4, NH2)
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428
GOLOVCHENKO et al.
Table 1. (Contd.)
.
1
IR spectrum, , cm
1H NMR spectrum, , ppm (J, Hz)
XIIIe 3280, 3420 (NH2)
XIIIfb 3280, 3420 (NH2)
XIIIg 3280, 3390 (NH2)
2.54 s (3H, CH3), 7.34 br.s (2H, NH2), 7.49 7.82 m (5H, C6H5)
2.39 s (3H, CH3), 2.43 s (3H, CH3), 7.28 8.00 m (10H, 2C6H4, NH2)
2.37 s (3H, CH3), 2.53 s (3H, CH3), 7.15 br.s (2H, NH2), 7.28 7.70 m
(4H, C6H4)
2.34 s (3H, CH3), 2.41 s (3H, CH3), 6.97 br.s (2H, NH2), 7.37 7.93 m
(4H, C6H4)
XIIIhc 3280, 3410 (NH2)
XIIIi 3280, 3440 (NH2)
2.31 s (3H, CH3), 2.49 s (3H, CH3), 6.76 br.s (2H, NH2)
a 13
1
2
C NMR spectrum of XIIId (DMSO-d ),
, ppm (Ht = 2-R -5-amino-1,3-oxazol-4-yl and Ht = 5-R -1,3,4-oxadiazol-2-yl):
C
6
3
4
2
5
2
5
b
21.13 (CH ), 98.27 (C ), 120.83 141.47 (C ), 150.18 (C ), 156.89 (C ), 159.83 (C ), 161.75 (C ). Mass spectrum, m/z:
332 [M] , 318, 199, 169, 144, 117, 90, 65.
(C H CH ), 96.25 (C ), 120.89 141.31 (C ), 150.34 (C ), 156.42 (C ), 159.93 (C ), 161.35 (C ).
Ht
Ar
Ht
Ht
Ht
Ht
+
c 13
C NMR spectrum of XIIIh [(CD ) SO],
, ppm: 13.05 (Ht CH ), 21.03
3 2
C
3
4
2
5
2
5
6
4
3
Ht
Ar
Ht
Ht
Ht
Ht
Table 2. Constants, yields, and elemental analyses of IV, V, VII XI, and XIII
.
Found, %
Calculated, %
H (P)
mp, C (solvent for crystallization)
Formula
C
H (P)
N
C
N
IVa
IVb
IVc
Va
Vb
Vc
VIIa
VIIb
VIIc
VIId
VIIe
VIIf
VIIIa
VIIIb
VIIIc
VIIId
IXf
Xa
Xb
Xc
Xd
Xe
Xf
XIa
XIb
XIc
85
88
73
84
87
90
66
71
78
62
73
81
65
79
75
82
35
61
67
63
69
64
71
73
69
77
190 191 (methanol)
195 196 (methanol)
119 120 (ethanol)
104 105 (benzene)
120 121 (aqueous ethanol)
78 80 (benzene)
146 147 (benzene)
194 195 (methanol)
170 172 (ethanol)
127 129 (benzene)
153 154 (benzene)
187 189 (methanol)
134 136a
57.04
58.43
58.51
5.06
5.53
5.41
(10.84) 14.67
(10.12) 13.86
(9.91)
4.61
5.11
5.06
5.02
5.37
5.12
18.37
17.19
16.85
C11H11N3O3
C12H13N3O3
C12H13N3O3
C11H14N3O4P
C12H16N3O4P
C13H18N3O4P
C18H15N3O4
C19H17N3O4
C19H17N3O4
C19H17N3O4
C20H19N3O4
C20H19N3O4
C18H18N3O5P
C20H22N3O5P
C21H24N3O5P
C19H20N3O5P
C19H16N4O2
C18H15N3O4
C19H17N3O4
C19H17N3O4
C19H17N3O4
C20H19N3O4
C20H19N3O4
C18H18N3O5P
C20H22N3O5P
C21H24N3O5P
56.65
58.29
58.29
4.75
5.30
5.30
(10.94) 14.84
(10.42) 14.14
(9.95) 13.50
4.48
4.88
4.88
4.88
5.24
5.24
4.68
(7.46) 10.12
(7.21) 9.79
(7.72) 10.47
4.85
4.48
4.48
4.88
4.88
5.24
5.24
4.68
18.02
17.00
17.00
13.45
12.31
11.90
11.78
12.16
11.67
11.37
10.67
10.25
10.01
10.56
16.69
12.54
12.07
12.15
12.09
11.38
11.41
10.91
10.25
10.03
64.33
65.08
65.09
65.14
65.91
65.89
56.04
64.09
64.95
64.95
64.95
65.74
65.74
55.82
12.46
11.96
11.96
11.96
11.50
11.50
10.85
4.89
158 159a
(7.61)
(7.15)
(7.91)
4.98
4.63
5.03
5.12
5.07
5.41
5.38
150 152a
155 157a
>260b
68.83
64.27
65.12
65.16
65.09
65.89
65.83
55.98
68.66
64.09
64.95
64.95
64.95
65.74
65.74
5.82
16.86
12.46
11.96
11.96
11.96
11.50
11.50
10.85
136 137 (ethanol)
126 127 (ethanol)
115 116 (ethanol)
119 120 (ethanol)
132 133 (ethanol)
133 134 (ethanol)
150 151 (benzene hexane)
158 159 (aqueous ethanol)
140 142 (aqueous ethanol)
4.79
(7.31)
(7.08)
(7.46) 10.12
(7.21) 9.79
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TRANSFORMATIONS OF ACYLATION PRODUCTS
Found, %
429
Table 2. (Contd.)
.
Calculated, %
H (P) N
mp, C (solvent for crystallization)
Formula
C
H (P)
N
C
XId
63
86
89
62
81
65
89
63
65
52
147 148 (benzene hexane)
231 232 (DMF acetonitrile)
238 239 (DMF acetonitrile)
182 184 (ethanol)
241 242 (DMF acetonitrile)
227 228 (acetonitrile)
253 254 (DMF acetonitrile)
193 194 (ethanol)
251 253 (acetonitrile)
(7.91)
4.15
4.58
4.33
4.67
4.29
4.97
4.89
5.01
4.62
10.63
18.27
17.51
22.97
17.73
23.37
16.65
21.98
21.63
31.46
C19H20N3O5P
C17H12N4O2
C18H14N2O2
C12H10N2O2
C18H14N4O2
C12H10N4O2
C19H16N4O2
C12H10N4O2
C13H12N4O2
C7H8N4O2
(7.22) 10.47
XIIIa
XIIIb
XIIIc
XIIId
XIIIe
XIIIf
XIIIg
XIIIh
XIIIi
67.32
68.11
59.83
68.07
58.89
68.91
60.81
61.16
46.81
67.10
67.92
59.50
67.92
59.50
68.66
60.93
60.93
46.67
3.98
4.43
4.16
4.43
4.16
4.85
4.72
4.72
4.48
18.41
17.60
23.13
17.60
23.13
16.86
21.86
21.86
31.10
146 147 (aqueous ethanol)
a
b
Compounds VIIIa VIIId are unstable, and therefore they were not recrystallized.
After washing with ethanol.
1
IX
XII
XIII can be traced by H NMR and
the 1,3,4-oxadiazole fragment are widely used in
the search for bioactive agents. In this connection,
further modification of compounds X and XI is of
doubtless interest; this will be the subject of fur-
ther studies.
IR spectroscopy (Table 1). Furthermore, the struc-
ture of one of the simplest representatives of com-
pounds XIII (R1 = R2 = CH3) in the form of the
dihydrate was determined by single crystal X-ray
diffraction (figure, Table 3). Owing to the symme-
try conditions in the crystal, the molecule is ideally
planar (all the nonhydrogen atoms occupy special
positions on plane m). The N4 atom has a trigonal
planar configuration: The sum of the bond angles
at this atom is 360.0 within the experimental
error. Owing to very efficient n(N4) (C3=C4) con-
jugation, the N4 C4 bond [1.320(3) ] is apprecia-
EXPERIMENTAL
The IR spectra were recorded on a Specord
1
M-80 spectrometer (KBr pellets). The H and 13C
NMR spectra were measured on a Varian VXR-
300 spectrometer at 300 and 75 MHz, respectively
(solvent DMSO-d6, reference TMS). The mass
spectrum of XIIIf was taken with a Varian MAT-
311A device.
2
2
bly shortened compared to a single Nsp Csp bond
(typical length 1.43 1.45
[7, 8]). The short dis-
tance N2 N4 suggests formation of an intramolec-
The single crystal X-ray diffraction study of
XIIIi 2H2O (crystal size 0.25 0.31 0.43 mm)
was performed at room temperature with an
ular hydrogen bond N2 H41 N4 [N2 N4 3.064(3),
N2 H41 2.51(3)
six-membered ring.
,
N2H41N4 121(2) ] closing a
H41 N4
Thus, there is no doubt that heating of accessi-
ble substrates VI with carboxylic acid chlorides in
pyridines involves succesive, quite regioselective
C4
N2
O2
transformations VI
IX
XII
XIII, allowing
one-pot synthesis of previously unknown 2-(5-ami-
no-1,3-oxazol-4-yl)-1,3,4-oxadiazole derivatives in
high yield.
N1
C1
C2 C3
C5
Of no less importance are also the preparative
syntheses of glycine (X) and aminomethylphos-
phonic acid (XI) derivatives containing a 1,3,5-oxa-
diazole ring at the asymmetric center. Such trans-
C6
N3
O1
C7
formations of
-amino phosphonic [19 24] acids containing
residues of other nitrogen heterocycles instead of
-amino carboxylic [9 18] and
General view of the molecule of XIIIi in the crystal of
XIIIi 2H O (water molecules are not shown).
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

430
GOLOVCHENKO et al.
Table 3. Selected bond lengths (d, ) and bond angles
( , deg) in XIIIi 2H2O
IIc in 30 ml of THF, we added 0.035 mol of hy-
drazine hydrate. The mixture was allowed to stand
for 24 h at 20 25 C. The precipitate was filtered
off, washed with a minimal amount of water, and
mixed with the substance obtained from the THF
filtrate. For analysis, the product was dried and
recrystallized from appropriate solvent. Com-
pound Va was prepared previously [28].
Bond
d
Angle
O1 C1
O1 C2
N1 C1
N1 N2
N2 C2
O2 C4
O2 C5
N3 C3
N3 C5
N4 C4
C2 C3
C3 C4
1.364(2)
1.359(3)
1.281(3)
1.415(3)
1.294(3)
1.365(3)
1.383(3)
1.406(3)
1.282(3)
1.320(3)
1.434(3)
1.355(3)
C1O1C2
C4O2C5
N2N1C1
N1N2C2
C3N3C5
O1C1N1
O1C2N2
N3C3C4
O2C4C3
O2C5N3
102.9(1)
104.8(2)
107.0(2)
105.3(2)
104.9(2)
112.1(2)
112.7(2)
109.0(2)
107.7(2)
113.5(2)
2-Aryl(methyl)-5-hydrazino-1,3-oxazole-4-carbo-
nitriles VIa VIc was prepared by the published
procedure [1, 2].
Alkyl 2-aryl-5-(2-acylhydrazino)-1,3-oxazole-4-
carboxylates VIIa VIIf. To a solution of 0.01 mol
of IVa IVc in 15 ml of anhydrous acetonitrile, we
added 0.025 mol of anhydrous triethylamine and
then 0.0105 mol of appropriate acyl chloride. The
mixture was allowed to stand for 24 h at 20 25 C,
after which 50 ml of water was added, and the
precipitate was filtered off, dried, and recrystal-
lized from appropriate solvent.
Enraf-Nonius CAD-4 automatic four-circle diffrac-
tometer (CuK radiation,
1.54178 , scanning
70 , sphere segment 0
7, 30 max
l 30). A total of 2268 re-
rate ratio 2 / 1.2,
Dialkyl 2-aryl-5-(2-acylhydrazino)-1,3-oxazol-
4-ylphosphonates VIIIa VIIId. To a solution of
0.01 mol of Va Vc in 10 ml of anhydrous aceto-
nitrile, we added 0.025 mol of anhydrous triethyl-
amine and 0.0105 mol of appropriate acyl chloride.
The mixture was allowed to stand for 24 h at 20
25 C, and the precipitate was filtered off, washed
with water, combined with the product obtained
from the filtrate, and used for further transforma-
tions without additional purification.
h
7, 0
k
flections were measured; 1046 of them were unique
(Rint 0.015). The crystals are rhombic; a 6.627(1),
b 6.274(2), c 24.834(6) ; V 1032.6(4) 3, M 216.2,
3
1
Z 4, dcalc 1.39 g cm ,
9.43 cm , F(000) 457.6,
space group Pmna (no. 53). The structure was
solved by the direct method and refined by the
least-squares method in the full-matrix anisotropic
approximation using the CRYSTALS program
package [25]. In the refinement, we used 800 re-
flections with I > 3 (I) (111 refined parameters, 7.2
reflections per parameter); all the hydrogen atoms
were revealed by the differential electron density
synthesis and refined positionally with fixed ther-
mal parameters. We used the Chebyshev scheme
[26] with five parameters: 3.89, 4.66, 4.09, 1.27,
and 0.78. The final divergence factors were R 0.040
and RW 0.043; GOF 1.129. The residual electron
density from the differential Fourier series is 0.24
and 0.32 e 3. The absorption in the crystal was
taken into account by azimuthal scanning [27].
2-p-Tolyl-5-(2-p-toluylhydrazino)-1,3-oxazole-
4-carbonitrile IXf. To a solution of 0.01 mol of
IVb in 20 ml of anhydrous pyridine, we added
0.0105 mol of p-toluyl chloride. The mixture was
allowed to stand for 24 h at 20 25 C; 70 ml of
water was added, and the precipitate was filtered
off and washed with ethanol.
Alkyl 5-aryl-1,3,4-oxadiazol-2-yl(acylamino)ace-
tic acids Xa Xf. A solution of 0.01 mol of VIIa
VIIf in 15 ml of glacial acetic acid was heated
for 8 h at 110 120 C. The solvent was vacuum-
evaporated, and the oily residue was treated with
water for crystallization. The precipitate was fil-
tered off and recrystallized from appropriate sol-
vent.
Alkyl 2-aryl-5-hydrazino-1,3-oxazole-4-carbox-
ylates IVa IVc. To a solution of 0.01 mol of Ia or
Ib in 30 ml of methanol, we added 0.035 mol of
hydrazine hydrate. The mixture was allowed to
stand for 24 h at 20 25 C. The precipitate of IVa
or IVb was filtered off, washed with water, dried,
and recrystallized from appropriate solvent. Com-
pound IVc was prepared similarly using ethanol
instead of methanol.
Dialkyl 5-aryl-1,3,4-oxadiazol-2-yl(acylamino)-
methylphosphonates XIa XId.
A
solution of
0.01 mol of VIIIa VIIId in 10 ml of 80% ethanol
was heated for 30 min. The precipitate was filtered
off and recrystallized from appropriate solvent.
Dialkyl 2-aryl-5-hydrazino-1,3-oxazol-4-ylphos-
phonates Va Vc. To a solution of 0.01 mol of IIa
2-[5-Amino-2-aryl(methyl)-1,3-oxazol-4-yl]-5-
aryl(methyl)-1,3,4-oxadiazoles XIIIa XIIIi. a. To
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

TRANSFORMATIONS OF ACYLATION PRODUCTS
a solution of 0.01 mol of VIa VIc in 20 ml of anhy- Sect. B, 1976, vol. 32, no. 12, p. 3216.
431
drous pyridine, we added 0.0105 mol of appropri-
ate acyl chloride. The mixture was heated for 8 h
at 110 120 C. The solvent was removed in a vacu-
um, and the oily residue was treated with water for
crystallization. The precipitate was filtered off,
dried, and recrystallized from appropriate solvent.
In the synthesis of XIIIi, the oily residue was dis-
solved in water, and crystals of XIIIi 2H2O formed
in 48 h. A crystal of this product was selected for
an X-ray diffraction study. For analysis, the sol-
vate was dried in a vacuum desiccator over P2O5.
9. Whitlock, B.J., Lipton, S.H., and Strong, F.M., J. Org.
Chem., 1965, vol. 30, no. 1, p. 115.
10. Eugster, C.H., Muller, G.F.R., and Good, R., Tetra-
hedron Lett., 1965, no. 23, p. 1813.
11. Myers, A.G. and Gleason, J.L., J. Org. Chem., 1996,
vol. 61, no. 2, p. 813.
12. Matzen, L., Engesgaard, A., Ebert, B., Didriksen, M.,
Frolund, B., Krogsgaard-Larsen, P., and Jaroszew-
ski, J.W., J. Med. Chem., 1997, vol. 40, no. 4, p. 520.
13. Adlington, R.M., Baldwin, J.E., Catteric, D., and
Pritchard, G.J., J. Chem. Soc., Perkin Trans. 1, 1999,
no. 8, p. 855.
14. Adlington, R.M., Baldwin, J.E., Catteric, D., and
Pritchard, G.J., J. Chem. Soc., Perkin Trans. 1, 2000,
no. 3, p. 299.
15. Jones, R.C.F., Berthelot, D.J.C., and Iley, J.N., Chem.
Commun., 2000, no. 21, p. 2131.
16. Adlington, R.M., Baldwin, J.E., Catteric, D., Prit-
chard, G.J., and Tang, L.T., J. Chem. Soc., Perkin
Trans. 1, 2000, no. 15, p. 2311.
b. A mixture of 0.01 mol of VIa or VIb with 4 g
of benzoic anhydride was heated for 8 h at 130 C
and then allowed to stand for 12 h at 20 25 C,
after which 15 ml of acetonitrile was added, and
the mixture was heated to reflux. The precipitate
was filtered off and recrystallized from dimethyl-
formamide acetonitrile, 1 : 1. Yields: XIIIa 76%
and XIIIb 83%. Mixing of the samples of XIIIa
prepared by procedures a and b gave no depres-
1
sion of the melting point. The H NMR spectra of
17. Adlington, R.M., Baldwin, J.E., Catteric, D., and
Pritchard, G.J., J. Chem. Soc., Perkin Trans. 1, 2001,
no. 7, p. 668.
these samples, and also of the two samples of XIIIb
prepared by procedures a and b, were identical.
18. Stensbol, T.B., Uhlmann, P., Morel, S., Eriksen, B.L.,
Felding, J., Kromann, H., Hermit, M.B., Green-
wood, J.R., Brauner-Osborne, H., Madsen, U., Juna-
ger, F., Krogsgaard-Larsen, P., Begtrup, M., and
Vedso, P., J. Med. Chem., 2002, vol. 45, no. 1, p. 19.
19. Aminophosphonic and Aminophosphinic Acids Che-
mistry and Biological Activity, Kukhar, V.P. and
Hudson, H.R., Eds., Chichester: Wiley, 2000.
20. Boduszek, B., Phosphorus, Sulfur, Silicon, 1995,
vol. 104, p. 63.
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