Synthesis and Transformations of 4-Phosphorylated 2-Alkyl(aryl)-5-hydrazinooxazoles

Article abstract of DOI:10.1023/A:1013982122431

Treatment of 1-phosphorylated 2,2-dichloroethenylcarboxamides with excess hydrazine hy-drate gives in high yields phosphorylated derivatives of 2-alkyl(aryl)-5-hydrazinooxazoles containing the P(O)(OCH3)2, P(O)(OC2H5)2, and P⁺(C6H5)3ClO4^- groups in the 4-position of the ring. The presence of the hydrazine group in these oxazole derivatives was confirmed not only by the spectral data, but also by the reactions with p-toluic aldehyde, p-toluic chloride, and phenyl isothiocyanate.

Full text of DOI:10.1023/A:1013982122431

Russian Journal of General Chemistry, Vol. 71, No. 11, 2001, pp. 1726 1728. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 11, 2001,
pp. 1822 1824.
Original Russian Text Copyright
2001 by Brovarets, Vydzhak, Pil’o, Zyuz’, Drach.
Synthesis and Transformations
of 4-Phosphorylated 2-Alkyl(aryl)-5-hydrazinooxazoles
V. S. Brovarets, R. N. Vydzhak, S. G. Pil’o, K. V. Zyuz’, and B. S. Drach
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received August 4, 2000
Abstract Treatment of 1-phosphorylated 2,2-dichloroethenylcarboxamides with excess hydrazine hy-
drate gives in high yields phosphorylated derivatives of 2-alkyl(aryl)-5-hydrazinooxazoles containing the
P(O)(OCH3)2, P(O)(OC2H5)2, and P+(C6H5)3ClO4 groups in the 4-position of the ring. The presence of
the hydrazine group in these oxazole derivatives was confirmed not only by the spectral data, but also by
the reactions with p-toluic aldehyde, p-toluic chloride, and phenyl isothiocyanate.
Reaction of three types of phosphorus-containing
electrophilic reagents I III with amines is thoroughly
studied [1 3]. In this work we found that compounds
I III readily react not only with amines, but also
with hydrazine hydrate. The reaction yields phos-
phorus-containing 5-hydrazinooxazoles IV and V
ample, comparison of the IR spectra of the initial
compounds I III and the products of their reaction
with hydrazine hydrate IV and V suggests disap-
pearance of the carbonyl group of the amide moiety
which takes part in cyclization. At the same time,
the H NMR spectra of IV and V contain a broad
singlet of two protons of the NNH2 group in the range
4.2 4.8 ppm.
1
1
whose structure was confirmed by the IR and H
NMR spectra (see Experimental; Table 1). For ex-
R = C6H5 (Ia VIa, Ib, IIb, VIb, VII, VIIIa), 4-ClC6H4 (Ic, IIIc Vc, VIIIc), CH3 (Id, IVd, VId), C6H5CH=CH (Ie, IVe);
Alk = CH3 (Ia, Ic, Id, IIa), C2H5 (Ib, IIb); +R = C6H5 (Xa), CH2=CHCH2 (Xb);
IVd, VIa, VId), P(O)(OC2H5)2 (IVb, VIb), PPh3ClO4 (Va, Vc, VII).
= P(O)(OCH3)2 (IVa, IVc,
1070-3632/01/7111-1726$25.00 2001 MAIK Nauka/Interperiodica

SYNTHESIS AND TRANSFORMATIONS OF 4-PHOSPHORYLATED 2-ALKYL
Table 1. 1H NMR spectra of IV IX
1727
Comp. no.
, ppm (DMSO-d6)
3.69 d (6H, 2CH3O, JHP 12.1 Hz), 4.80 br.s (2H, NH2), 7.48 7.84 m (6H, C6H5, NH)
3
IVa
IVe
Va
3
3.67 d (6H, 2CH3O, JHP 12.0 Hz), 4.75 br.s (2H, NH2), 7.03 7.64 m (8H, C6H5, CH=CH, NH)
4.20 br.s (2H, NH2), 7.48 7.95 m (21H, 4C6H5, NH), 9.82 br.s (1H, NH)
3
VIa
2.35 s (3H, CH3), 3.74 d (6H, 2CH3O, JHP 11.9 Hz), 7.25 7.80 m (9H, C6H5, C6H4), 8.35 s
(1H, CH=N), 10.86 s (1H, NH)
VIb
VId
1.27 t (6H, 2CH3), 2.35 s (3H, CH3), 4.07 q (4H, 2CH2O), 7.28 7.95 m (9H, C6H5, C6H4),
8.29 s (1H, CH=N), 10.75 s (1H, NH)
2.38 d (6H, 2CH3O, JHP 12.5 Hz), 3.63 s (3H, CH3), 3.70 s (3H, CH3), 7.23 7.53 m
3
(4H, C6H4), 8.18 s (1H, CH=N), 10.35 s (1H, NH)
VII
VIIIa
2.21 s (3H, CH3), 6.46 7.95 m (25H, 4C6H5, C6H4, CH=N), 12.79 br.s (1H, NH)
2.38 s (3H, CH3), 3.73 d (6H, 2CH3O, JHP 11.6 Hz), 7.35 7.88 m (9H, C6H5, C6H4),
3
8.65 br.s (1H, NH), 10.71 br.s (1H, NH)
3
VIIIc
IX
2.38 s (3H, CH3), 3.67 d (6H, 2CH3O, JHP 11.9 Hz), 7.40 7.84 m (8H, 2C6H4), 8.77 s
(1H, NH), 10.75 s (1H, NH)
2.26 s (3H, CH3), 2.36 s (3H, CH3), 7.13 7.88 m (28H, 4C6H5, 2C6H4), 11.95 br.s (1H, NH)
Table 2. Constants, yields, and elemental analyses of IV X
Found, %
Calculated, %
Cl (S) P
Comp. Yield,
no.
mp,
C
Formula
%
(solvent for crystallization)
Cl (S)
10.96
N
P
N
IVa
84a 104 105 (benzene)
14.67 10.81 C11H14N3O4P
13.39
13.15
18.88 13.86 C6H12N3O4P
13.58
7.83
7.15
10.71
10.15
12.90
6.45
9.65
8.91
14.84 10.94
b
IVb
IVc
IVd
IVe
Va
77a
9.81 C13H18N3O4P
9.60 C11H13ClN3O4P
13.50
13.23
9.95
9.75
86
72
75
78
82
79
83
72
85
82
74
68
77
69
48 50 (aqueous methanol)
11.16
b
19.00 14.01
13.59 10.02
118 120 (benzene)
9.90 C13H16N3O4P
5.67 C27H23ClN3O5P
5.35 C27H22Cl2N3O5P
7.92 C19H20N3O4P
7.40 C21H24N3O4P
9.43 C14H18N3O4P
4.79 C35H29ClN3O5P
7.05 C19H20N3O5P
6.52 C19H19ClN3O5P
3.93 C43H35ClN3O7P
7.39 C18H19N4O4PS
7.90 C15H19N4O4PS
206 209c (methanol)
208 210c (methanol)
118 120 (ethanol)
6.49
12.65
6.62
12.43
7.84
7.37
10.90
10.16
13.00
6.59
9.72
9.00
5.44
5.78
5.43
8.04
7.49
9.58
4.85
7.16
6.64
4.01
7.40
8.10
Vc
VIa
VIb
VId
VII
VIIIa
VIIIc
IX
136 137 (ethanol)
120 121 (aqueous ethanol)
230 232c (ethanol)
5.39
5.56
155 158 (methanol)
152 155 (acetonitrile)
238 242c (acetonitrile)
145 147 (aqueous ethanol)
75 80 (aqueous ethanol)
7.63
4.45
7.60
4.59
(7.66) 13.39
(8.39) 14.65
5.32
(7.53) 13.28
(8.25) 14.51
Xa
Xb
a
b
c
Yield in procedure a.
The product was isolated as a viscous oil.
Melts with noticeable decomposition.
Also, similarly to other alkyl, aryl, and heteryl-
hydrazines, compounds IV and V readily react with
aldehydes, acid chlorides, and aryl isothiocyanates
possible to obtain not only compounds VI X, but
also numerous other derivatives, because compounds
I III are readily available, and their cyclocon-
densation with hydrazine hydrate proceeds quite selec-
tively.
(see the transformations IV
VI, V
VII, IV
VIII, and V IX or X in the scheme).
It is quite evident that from the two new types
of phosphorylated heterylhydrazines IV and V it is
The yields and physicochemical characteristics of
the obtained products are listed in Table 2.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

1728
BROVARETS et al.
EXPERIMENTAL
the precipitate was filtered off, and compound VII
was purified by crystallization. IR spectrum, , cm :
1
The IR spectra were recorded on a UR-20 spec-
trometer in KBr pellets. The H NMR spectra were
1640 (C=N), 3200 (NHassoc).
1
2-Aryl-4-dimethoxyphosphoryl-5-(2-p-toluylhy-
drazino)oxazoles VIIIa and VIIIc. To a solution of
0.005 mol of IVa or IVc in 15 ml of anhydrous
acetonitrile were added 0.005 mol of triethylamine
and 0.005 mol of p-toluyl chloride. The mixture was
left for 48 h at 20 25 C, and the precipitate was
filtered off and washed with water. Compound VIIIa
or VIIIc was purified by crystallization. IR spectrum
recorded on a Varian VXR-300 spectrometer in
DMSO-d6 relative to TMS.
2-Alkyl(aryl)-5-hydrazino-4-dialkoxyphosphoryl-
oxazoles IVa IVe. a. To a solution of Ia Ie in 15 ml
of THF was added 0.045 mol of hydrazine hydrate.
The resulting mixture was stirred for 72 h at 20 25 C,
the solvent was removed in a vacuum, and the residue
was treated with water. Compounds IVa, IVc, and
IVe were purified by crystallization. Compounds IVb
and IVd were extracted from the aqueous emulsion
with methylene chloride and dried over sodium sul-
fate, the solvent was removed in a vacuum, and the
resulting viscous oil was used in further reactions
without additional purification. The IR spectra of
IVa IVe contain no intense bands in the range 1620
1
of VIIIa, , cm : 1680 (C=O), 3250 (NHassoc).
5-[(1,2-Di-p-toluyl)hydrazino]-4-triphenylphos-
phonio-2-phenyloxazole perchlorate IX. To a sus-
pension of 0.002 mol of phosphonium salt Va in
10 ml of anhydrous acetonitrile, 0.0042 mol of tri-
ethylamine and then 0.004 mol of p-toluyl chloride
were added at cooling with ice-cold water. The mix-
ture was left for 1 h at 20 25 C, 5 ml of diethyl ether
was added, the precipitate was filtered off and washed
with water, and phosphonium salt IX was purified by
1
1750 cm .
b. To a solution of IIa or IIb in 15 ml of THF was
added 0.035 mol of hydrazine hydrate, and compound
IVa or IVb was isolated as described above in
a 70 80% yield. The mixed sample of two prepara-
tions of IVa obtained by procedures a and b gave no
depression of the melting point.
1
crystallization. IR spectrum, , cm : 1690 (C=O),
1720 (C=O), 3300 (NHassoc).
4-Dimethoxyphosphoryl-2-phenyl-5-(4-phenyl-
thiosemicarbazido)oxazole Xa. To a solution of
0.003 mol of IVa in 10 ml of acetonitrile was added
0.0036 mol of phenyl isothiocyanate. The mixture was
refluxed for 3 h, the precipitate was filtered off, and
compound Xa was purified by crystallization.
(2-Aryl-5-hydrazinooxazol-4-yl)triphenylphos-
phonium perchlorates Va and Vc. To a solution of
0.02 mol of phosphonium salt IIIa or IIIc in 25 ml of
methanol was added 0.03 mol of hydrazine hydrate.
The resulting mixture was left for 12 h at 20 25 C,
the precipitate was filtered off, and 0.5 ml of acetic
acid and 5 ml of saturated aqueous solution of sodium
perchlorate were added. The precipitate was filtered
off, and compound Va or Vc was purified by crys-
tallization.
5-(4-Allylthiosemicarbazido)-4-dimethoxyphos-
phoryl-2-phenyloxazole Xb was obtained similarly
to Xa from substituted 5-hydrazinooxazole IVa and
allyl isothiocyanate.
ACKNOWLEDGMENTS
p-Toluic aldehyde 2-[4-dialkoxyphosphoryl-2-
methyl(phenyl)oxazol-4-yl]hydrazones VIa, VIb,
and VId. A mixture of 0.001 mol of compound IVa,
IVb, or IVd, 0.001 mol of p-toluic aldehyde, and
10 ml of ethanol was refluxed for 3 h, the solvent was
removed in a vacuum, and compound VIa, VIb, or
VId was purified by crystallization.
The authors are grateful to the State Foundation for
Basic Research of Ukraine (project no 3.4/26) for
the financial support.
REFERENCES
1. Drach, B.S. and Sviridov, E.P., Zh. Obshch. Khim.,
1973, vol. 43, no. 7, pp. 1648 1649.
p-Toluic aldehyde 2-[4-triphenylphosphonio-2-
phenyloxazol-4-yl]hydrazone perchlorate (VII). To
a solution of 0.001 mol of phosphonium salt Va
in 10 ml of ethanol was added 0.001 mol of p-toluic
aldehyde. The resulting mixture was refluxed for 3 h,
2. Drach, B.S., Sviridov, E.P., and Shaturskii, Ya.P.,
Zh. Obshch. Khim., 1974, vol. 44, no. 8, pp. 1712 1715.
3. Drach, B.S., Sviridov, E.P., and Kirsanov, A.V.,
Zh. Obshch. Khim., 1975, vol. 45, no. 1, pp. 12 16.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001