One-pot synthesis of (5-aminopyrazol-4-yl)-phosphonic acid derivatives from 1-aryl-5-arylcarboxamidopyrazoles through pyrazolo[4,3-c][1,5,2]-oxazaphosphinines

Article abstract of DOI:10.1055/s-2003-38685

1-Aryl-5-arylcarboxamidopyrazoles react with phosphorus(III) halides giving the new heterocyclic system: pyrazolo[4,3-c][1,5,2]oxazaphosphinine. Treatment of pyrazolo[4,3-c][1,5,2]oxazaphosphinines with nucleophilic or electrophilic reagents leads to a cleavage of the oxazaphosphinine ring yielding derivatives of (5-aminopyrazol-4-yl)phosphonic acid.

Full text of DOI:10.1055/s-2003-38685

906
PAPER
One-Pot Synthesis of (5-Aminopyrazol-4-yl)-phosphonic Acid Derivatives
from 1-Aryl-5-arylcarboxamidopyrazoles through Pyrazolo[4,3-c][1,5,2]-
oxazaphosphinines
S
ynthesis of (5-A
m
m
inopyrazol-4-yl)-
p
i
hospho
t
nic Aci
r
d Deriva
i
tives y M. Volochnyuk,*a Alexei O. Pushechnikov,a Dmitriy G. Krotko,a Georgiy N. Koydan,a Anatoliy P.
Marchenko,a Alexander N. Chernega,a Alexander M. Pinchuk,a Andrei A. Tolmachevb
a
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanskaya 5, Kyiv-94, 02094, Ukraine
Fax +380(44)2696794; E-mail: dov@fosfor.kiev.ua
b
Research and Development Center for Chemistry and Biology, National Taras Shevchenko University, 62 Volodymyrska st., Kyiv-33,
01033, Ukraine
Received 6 February 2003
In a previous work, we reported on phosphorylation of
Abstract: 1-Aryl-5-arylcarboxamidopyrazoles react with phos-
some electron-rich aminoheterocycles including 5-ami-
phorus(III) halides giving the new heterocyclic system: pyrazo-
lo[4,3-c][1,5,2]oxazaphosphinine. Treatment of pyrazolo[4,3-
c][1,5,2]oxazaphosphinines with nucleophilic or electrophilic re-
nopyrazole using formamidine function as protecting
group.6,10,11 It was considered for sometime that classical
agents leads to a cleavage of the oxazaphosphinine ring yielding de- acyl protecting of amino group was unsuitable for the
rivatives of (5-aminopyrazol-4-yl)phosphonic acid.
phosphorylation because of the high reaction ability of the
amide function towards phosphorus(III) halides.12 How-
Key words: 1-aryl-5-arylcarboxamidopyrazoles, phosphorus(III)
halides, phosphorylation, heterocyclization, ring opening
ever we have recently found that using an acyl group as a
protecting group for phosphorylation with 1,1-bielectro-
philic phosphorus(III) halides leads to formation of fused
1,5,2-oxazaphosphinine ring systems. For example, N-
acyl-N ,N -dimethyl-1,3-benzenediamine is phosphory-
lated with PBr3 giving 2,4,1-benzoxazaphosphinine ring
systems. Hydrolysis of 1-arylimino-2,4,1-benzoxaza-
phosphinines leads to cleavage of an oxazaphosphinine
ring yielding mixed amides of 2,4-diaminophenylphos-
phonic acid.13 In the present work, we apply our approach
to the synthesis of (5-aminopyrazol-4-yl)phosphonic acid
derivatives.
Pyrazoles are a class of heterocyclic compounds having
many derivatives with a wide range of interesting proper-
ties, such as drugs, pesticides, and new materials, amongst
others.1,2 In the past fifteen years derivatives of pyrazoles
were one of the general group of substances which were
used in the search for new insecticides and acaricides.
Among them the activity of 3,4-disubstituted derivatives
of 1-alkyl and 1-aryl-5-aminopyrazoles have been studied
in detail. As a result of these investigations, the highly ef-
fective insecticide fipronil, 5-amino-1-(2,6-dichloro-4-tri-
fluoromethylphenyl)-4-trifluoromethylsulfinyl-3-cyano-
pyrazole has been found.3 Besides this, it was established
that 5-aminopyrazoles bearing electron-withdrawing
groups in the 4 position including 4-phosphorylated 5-
aminopyrazoles have herbicidal properties.4 Continuing
our research in the direct phosphorylation of pyrazoles
with phosphorus(III) halides,5–9 we have given special
consideration to the synthesis of derivatives of 4-phos-
phorylated 5-aminopyrazoles.
1-Aryl-5-arylcarboxamidopyrazoles 1 react with phos-
phorus(III) halides forming the new heterocyclic system:
pyrazolo[4,3-c][1,5,2]oxazaphosphinine 3–5. We suggest
that heterocyclization runs through the acyclic O-phos-
phorylated intermediate 2 (Scheme 1).8,13,14
Pyrazolooxazaphosphinines 3–5, crystalline substances,
stable under inert atmosphere, are formed in a high yield.
Owing to the high rate and selectivity of the cyclization
reaction it is convenient to use substances 3–5 in situ as a
R
R
P
XP
i
O
O
O
N
N
N
Ar
N
N
N
Ar
N
N
N
Ar
H
Ph
Ph
Ph
1 a-d
2
3 a-d R = Br, δP = 155 ppm
4 a,b R = Ph, δP = 92 ppm
5 a,b R = 4-Me2N-C6H4, δP
90 ppm
Ar = a: Ph; b: 4-Cl-C6H4;
c: 3,4,5-(MeO)3C6H2; d: 4-F-C6H4.
=
Scheme 1 Reagents and conditions: (i) for 3: PBr3, Py, 15 min; for 4: PhPBr2, Py, 15 min or PhPCl2, Py, 30 h; for 5: 4-Me2N–C6H4–PCl2,
Py, 40 h.
Synthesis 2003, No. 6, Print: 29 04 2003.
Art Id.1437-210X,E;2003,0,06,0906,0914,ftx,en;P01303SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
Synthesis of (5-Aminopyrazol-4-yl)-phosphonic Acid Derivatives
907
H
H
OH
Ph
O
O
P
P
ii
i
i
H
H
1a
3a
4a
N
N
Ph
Ph
N
N
N
N
O
O
Ph
Ph
6
7
Scheme 2 Reagents and conditions: (i) air, 24 h; (ii) H2O, 30 °C.
pyridine solution for further transformation. Above-men- phorus(V) in a series of pyrazolooxazaphosphinines, can
tioned pyrazolooxazaphosphinines hydrolize with air/wa- be rationalized by high basicity of the phosphaza group.
ter with cleavage of an oxazaphosphinine ring yielding The protonation of the phosphaza group leads to phospho-
hydrophosphoryl compounds 6 and 7. It should be noted nium cation 14, which reacts with nucleophiles like in-
that phosphonic acid 6, unlike phosphinoxide 7 is hydrol- tramolecular Arbuzov’s rearrangement (Scheme 4).15
ysis sensitive and hydrolized under mild conditions with
cleavage of the C–P bond giving starting pyrazole 1
(Scheme 2).
Bromoanhydrides 3 also react with the equivalent amount
of alcohol or phenol giving corresponding cyclic esters
15, which were oxidized with elemental sulfur to
Upon treatment with secondary aliphatic amines or thioesters 16. Esters 15 undergo a ring opening with an
anilines, cyclic bromoanhydrides 3 undergo halogen sub- excess of alcohol with formation of acyclic esters 17.16
stitution yielding amides 8 and 9 respectively, which can Esters 17 hydrolized in air to the monoester of pyra-
be oxidized with elemental sulfur to give stable in air cy- zolylphosphonic acid 18 and oxidized to stable in air thio-
clic thioamides 10 and 11. Amides 8 react with arylazides phosphonates 19 by elemental sulfur (Scheme 5). Ester
giving iminoamides 12, which are hydrolysis sensitive 18, like acid 6, is hydrolized by water to starting acylami-
and hydrolized with water in the presense of base with nopyrazole 1a. The C–P bond of thiophosphonate 19 is
opening of a ring giving in a high yield mixed amides of also hydrolysis sensitive, but, unlike the substances 18
5-amino-4-pyrazolylphosphonic acid 13 (Scheme 3).
and 6, hydrolysis needs more drastic conditions. In this
case the hydrolysis runs in boiling aqueous HCl and, be-
sides the cleavage of C–P bond, the hydrolysis of amide
Hydrolytic instability of iminoamides 12, which is not
typical for the other derivatives of tetracoordinate phos-
Scheme 3 Reagents and conditions: (i) for 8: HNAlk2, Py; for 9: ArNH2, Py; (ii) S, Py; (iii) Ar N3, Py, 50 °C, 3 h; (iv) H2O, Py.
Scheme 4
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

908
D. M. Volochnyuk et al.
PAPER
Scheme 5 Reagents and conditions: (i) 1 equiv HOR, Py; (ii) S, Py; (iii) 4 equiv MeOH, Py; (iv) H2O, 4 °C.
function with formation of the corresponding arylcarbon- bromophosphonium bromides 27 are hydrolized with wa-
ic acid and 5-aminopyrazole also occurred.
ter in the presence of base giving cyclic phosphorus(V)
amides 28 (Scheme 7).
Cyclic phosphines 4 and 5 can also be transformed into
stable in air derivatives of phosphorus(V). For example,
they can be oxidized to thioxides 20 and 21 by elemental
sulfur and iminated with arylazides to cyclic phosphaza
compounds 22. The latter are hydrolized with ring open-
ing giving mixed amides of 5-amino-4-pyrazolylphos-
phinic acid 23 analogous to phosphaza compounds 12
(Scheme 6).
Cyclic pyrazolooxazaphosphinines with a trivalent phos-
phorus atom can react with halogens with formation of
haloidphosphonium salts. Thus, cyclic phosphine 4a re-
acts with chlorine giving chlorophosphonium chloride 24,
which under heating undergoes an intramolecular Arbu-
zov’s rearrangement17 giving acyclic derivatives 25. The
latter was transformed into stable in air amidine 26
(Scheme 6).
Scheme 7 Reagents and conditions: (i) Br2, Py; (ii) H2O, Py.
Bromination of anilides 9 leads to bromophosphaza com-
pound 29, which reacted with morpholine affording imi-
noamide 12aa. However, side processes accompany this
transformation and the isolation of the targeted products is
more difficult compared with the arylazide approach
(Scheme 8).
In the same way, derivatives of haloidphosphonium salts
with retention of the oxazaphosphinine ring can also be
obtained. Thus, the products of bromination of amides 8,
Scheme 6 Reagents and conditions: (i) S, Py; (ii) Ar N3, Py, 50 °C, 3 h; (iii) H2O, Py; (iv) Cl2, CH2Cl2, –78 °C, (v) 90 °C, without solvent, 4
h; (vi) 4 equiv PhNH2, CH2Cl2.
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of (5-Aminopyrazol-4-yl)-phosphonic Acid Derivatives
909
Scheme 8 Reagents and conditions: (i) Br2, Py; (ii) HN(CH2CH2)2O, Py; (iii) H2O, Py.
Our attempts to carry out hydrolysis of amide function on sence of intensive IR absorption band at around 1650
compounds 13 and 19 leaving the C–P bond intact were cm–1 (C=O). Pyrazolooxazaphosphinines do not exhibit
unsuccessful due to lability of C–P bond and harsh condi- IR absorption from 1600 to 2870 cm–1 and have the medi-
tions needed for removing the benzoyl protecting group.18 um intensive IR absorption from 1500 to 1600 cm–1.
IFA protecting group, which can be removed under mild
basic conditions,19 is a suitable group for this purpose. It
was illustrated by the synthesis of dimethyl ester of 5-ami-
no-3-methyl-1-phenyl-1H-4-pyrazolylphosphonic acid
31 (Scheme 9). In the case of dimethyl ester of 3-methyl-
1-phenyl-5-trifluoromethylcarboxamido-1H-4-pyrazolyl-
phosphonic acid 30 one-pot method for synthesis did not
work and synthesis was carried out in several steps.
Deprotection of the amino group was carried out with
N2H4 in methanol at room temperature.
It should be noted that reaction of opening cyclic esters
with an excess of alcohol is reversible. It was found dur-
ing an attempt to isolate acyclic ester 17e. The ester 17e is
stable in a methanol solution in the absence of water and
oxygen, however under evaporating methanol in vacuo
cyclic ester 15ae was isolated in low yield.
The structure of the new phosphorus substances was con-
firmed by NMR 1, 31 and 13, IR, mass-spectroscopy and el-
emental analysis. Also the structure of compound 10a was
confirmed by the single crystal X-ray diffraction study
(Figure 1). The absence of a signal for C(4)–H proton of
pyrazole ring at 5.5 ppm in the 1H NMR spectra and a sig-
nal with a considerable coupling constant (1JCP ~ 160–200
Figure 1. Molecular structure of 10a. Selected bond lengths (Å)
and angles: P(1)–S(1) 1.915(2), P(1)–O(2) 1.645(3), P(1)–N(1)
1.631(4), P(1)–C(8) 1.752(4), O(2)–C(3) 1.365(5), N(4)–C(3)
1.279(5), N(4)–C(9) 1.369(5), C(8)–C(9) 1.378(6); O(2)P(1)C(8)
Hz) for C(4) of pyrazole ring at around 100 ppm in the 13C
NMR spectra are the most convincing evidence for the
formation of the C–P bond. In the case of the bicyclic
98.2(2),
P(1)O(2)C(3)
129.6(3),
O(2)C(3)N(4)
124.3(4),
structure one observes the absence of the signal for an C(3)N(4)C(9) 117.5(4), P(1)C(8)C(9) 118.7(3), N(4)C(9)C(8)
1
130.4(4).
amide proton at 10 ppm in H NMR spectra and the ab-
Scheme 9 Reagents and conditions: (i) PBr3, Et3N, dioxane, r.t., 24 h; (ii) MeOH, Et3N, Et2O, –30 °C; (iii) MeOH, r.t.; (iv) r.t. reduce pres-
sure; (v) 80% H2O2, MeOH, –40 °C; (vi) N2H4 H2O, MeOH, r.t. 48 h.
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

910
D. M. Volochnyuk et al.
PAPER
Table 1 Yields, Melting Points and 1H, 31P NMR Data of Phosphorus Compoundsa and Starting N-acylaminopyrazoles
No.
Yields Mp
31P NMR,
(ppm), solvent
1H NMR, (ppm), J (Hz)
(%)b (°C)c
1ad 78
84
–
–
–
2.27 (3 H, s, CH3), 6.46 (1 H, s, CH), 7.35–7.45 (7 H, m, CH), 7.50 (1 H, t, 3JHH = 7.5 Hz, CH), 7.7
(2 H, d, 3JHH = 7.6 Hz, CH), 8.45 (1 H, s, NH)
1be 68
140
2.26 (3 H, s, CH3), 6.30 (1 H, s, CH), 7.30 (1 H, t, 3JHH = 7.5 Hz, CH), 7.44 (2 H, t, 3JHH = 7.5 Hz,
CH), 7.56 (4 H, m, CH), 7.89 (2H, d, 3JHH = 7.5 Hz, CH), 10.4 (1 H, s, NH)
1ce 87
202–
203
2.27 (3 H, s, CH3), 3.72 (3 H, s, OCH3), 3.82 (6 H, s, OCH3), 6.28 (1 H, s, CH), 7.22 (2 H, s, CH),
7.31 (1H, t, 3JHH = 7.6 Hz, CH), 7.45 (2 H, t, 3JHH = 7.6 Hz, CH), 7.54 (2 H, d, 3JHH = 7.5 Hz, CH),
10.3 (1 H, s, NH)
1dd 70
1ed 70
3ad 80
3ed 93
4ad 70
130
–
–
2.31 (3 H, s, CH3), 6.55 (1 H, s, CH), 7.10 (2 H, t, 3JHH = 3JHF = 8.4 Hz, CH), 7.44–7.46 (5 H, m,
CH), 7.72 (2 H, dd, 3JHH = 8.4, 4JHF = 5.1 Hz, CH), 8.14 (1 H, s, NH)
182–
185
2.29 (3 H, s, CH3), 6.46 (1 H, s, CH), 7.37 (2 H, d, 3JHH = 8.7 Hz, CH), 7.43–7.53 (3 H, m, CH), 8.59
(1 H, br s, NH)
153– 157, CHCl3
155
2.24 (3 H, s, CH3), 7.14 (2 H, t, 3JHH = 7.5 Hz, CH), 7.2–7.4 (4 H, m, CH), 7.70 (2 H, d, 3JHH = 7.8
Hz, CH), 7.93 (2 H, d, 3JHH = 8.4 Hz, CH)
71
–73
158, pentane
2.39 (3 H, s, CH3), 7.39 (1 H, t, 3JHH = 7.2 Hz, CH), 7.50 (2 H, t, 3JHH = 8.4 Hz, CH), 7.80 (2 H, d,
3JHH = 8.4 Hz, CH)
173– 92, CHCl3
174
2.10 (3 H, s, CH3), 7.0–7.16 (7 H, m, CH), 7.20–7.28 (4 H, m, CH), 7.74 (2 H, d, 3JHH = 8.4 Hz, CH),
7.77 (2 H, d, 3JHH = 7.2 Hz, CH)
6e
7d
70
53
183– 5.8 (d, 1JPH = 543 2.40 (3 H, s, CH3), 7.37 (1 H, t, 3JHH=7.5 Hz, CH), 7.45 (1 H, d, 1JPH = 543 Hz, PH), 7.40–7.65 (7 H,
185 Hz), CHCl3
m, CH), 7.88 (2 H, d, 3JHH = 6.9 Hz, CH), 10.52 (1 H, s, NH)
226 6.0 (d, 1JPH = 496 2.02 (3 H, s, CH3), 7.37–7.65 (11 H, m, CH), 7.73 (2 H, dd, 3JHH = 8.1, 3J;H = 14.0 Hz, CH), 7.93 (1
Hz), CHCl3
H, d, 1JPH = 496 Hz, PH), 7.93 (2 H, d, 3JHH = 7.2 Hz, CH)
10ad 75
10bd 72
11bad 31
175 63, CHCl3
2.50 (3 H, s, CH3), 3.38 (4 H, m, NCH2), 3.65 (4 H, m, OCH2), 7.38 (1 H, t, 3JHH = 7.5 Hz, CH), 7.42–
7.60 (5 H, m, CH), 7.92 (2 H, d, 3JHH = 7.5 Hz, CH), 8.18 (2 H, d, 3JHH = 8.4 Hz, CH)
177– 63, CHCl3
178
2.50 (3 H, s, CH3), 3.37 (4 H, m, NCH2), 3.64 (4 H, m, OCH2), 7.30–7.60 (5 H, m, CH), 7.88 (2 H,
d, 3JHH = 7.5 Hz, CH), 8.10 (2 H, d, 3JHH = 8.4 Hz, CH)
156– 56, Py
158
2.50 (3 H, s, CH3), 6.10 (1 H, d, 3JPNH = 9.9 Hz, NH), 6.67 (2 H, d, 3JHH = 7.2 Hz, CH), 6.90 (1 H, t,
3JHH = 7.2 Hz, CH), 7.11 (2 H, t, 3JHH = 7.5 Hz, CH), 7.38 (1 H, t, 3JHH = 7.6 Hz, CH), 7.41 (2 H, d,
3JHH = 8.4 Hz, CH), 7.50 (2 H, t, 3JHH = 7.6 Hz, CH), 7.88 (2 H, d, 3JHH = 7.6 Hz, CH), 8.07 (2 H, d,
3JHH = 8.4 Hz, CH)
11bbe 42
13aad 47
156– 54, Py
158
2.50 (3 H, s, CH3), 7.20 (1 H, m, CH), 7.27 (2 H, m, CH), 7.47 (2 H, m, CH), 7.60 (2 H, t, 3JHH = 7.5
Hz, CH), 7.69 (2 H, d, 3JHH = 8.7 Hz, CH), 7.86 (2 H, d, 3JHH = 7.8 Hz, CH), 8.14 (2 H, d, 3JHH = 8.7
Hz, CH), 9.01 (1 H, d, 3JPNH = 9.1 Hz, NH)
213– 11, CDCl3
215
2.07 (3 H, s, CH3), 2.86 (4 H, m, NCH2), 3.20 (4 H, m, OCH2), 6.20 (1 H, d, 3JPNH = 13 Hz, PNH),
6.65 (1 H, t, 3JHH = 7.8 Hz, CH), 6.73 (2 H, t, 3JHH = 7.8 Hz, CH), 6.86 (2 H, d, 3JHH = 7.8 Hz, CH),
7.37–7.65 (6 H, m, CH), 7.73 (2 H, dd, 3JHH = 7.5 Hz, CH), 7.93 (2 H, d, 3JHH = 6.9 Hz, CH), 10.26
(1 H, s, NH)
13cbe 56
194– 10, (CH3)2CO
197
0.89 [6 H, t, 3JHH = 6.9 Hz, N(CH2CH3)2], 2.17 (3 H, s, CH3), 2.36 (3 H, s, CH3), 3.04 [4 H, m,
N(CH2CH3)2], 3.72 (3 H, s, OCH3), 3.80 (6 H, s, OCH3), 6.90 (2 H, d, 3JHH = 6.0 Hz, CH), 7.03 (2
H, d, 3JHH = 6.0 Hz, CH), 7.17 (2 H, s, CH), 7.17 (1 H, d, 3JPNH = 12 Hz, PNH), 7.35 (1 H, t,
3JHH = 7.8 Hz, CH), 7.45 (2 H, t, 3JHH = 7.8 Hz, CH), 7.60 (2 H, d, 3JHH = 8.1 Hz, CH), 10.26 (1 H,
s, NH)
13dbe 53
15eaf 96
211 10, (CH3)2CO
0.88 [6 H, t, 3JHH = 6.9 Hz, N(CH2CH3)2], 2.17 (3 H, s, CH3), 2.35 (3 H, s, CH3), 3.12 [4 H, m,
N(CH2CH3)2], 6.93 (2 H, d, 3JHH = 6.0 Hz, CH), 7.01 (2 H, d, 3JHH = 6.0 Hz, CH), 7.21 (1 H, d,
3JPNH = 12 Hz, PNH), 7.34 (3 H, m, CH), 7.44 (2 H, t, 3JHH = 7.8 Hz, CH), 7.53 (2 H, d, 3JHH = 7.8
Hz, CH), 7.90 (2 H, dd, 3JHH = 8.4, 4JHF = 5.1 Hz, CH), 10.32 (1 H, s, NH)
46– 146, pentane
47
2.17 (3 H, s, CH3), 2.83 (3 H, d, 3JPH = 10.5 Hz, POCH3), 6.96 (1 H, td, 3JHH = 7.2, 4JHH = 1.8 Hz,
CH), 7.14 (2 H, t, 3JHH = 7.2 Hz, CH), 8.04 (2 H, dd, 3JHH = 7.2, 4JHH = 1.8 Hz, CH)
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of (5-Aminopyrazol-4-yl)-phosphonic Acid Derivatives
911
Table 1 Yields, Melting Points and 1H, 31P NMR Data of Phosphorus Compoundsa and Starting N-acylaminopyrazoles (continued)
No.
Yields Mp
31P NMR,
(ppm), solvent
1H NMR, (ppm), J (Hz)
(%)b (°C)c
16aad 43
126 69, CHCl3
2.56 (3 H, s, CH3), 3.90 (3 H, d, 3JPH = 15.9 Hz, OCH3), 7.39 (2 H, m, CH), 7.48 (2 H, t, 3JHH = 7.5
Hz, CH), 7.55 (2 H, t, 3JHH = 7.8 Hz, CH), 7.89 (2 H, d, 3JHH = 7.8 Hz, CH), 8.18 (2 H, d, 3JHH = 7.5
Hz, CH)
16abd 40
173 65, CHCl3
2.60 (3 H, s, CH3), 7.08 (2 H, d, 3JHH = 7.2 Hz, CH), 7.20 (1 H, t, 3JHH = 7.2 Hz, CH), 7.29 (2 H, t,
3JHH = 7.2 Hz, CH), 7.40 (1H, t, 3JHH = 7.5 Hz, CH), 7.45–7.65 (5 H, m, CH), 7.87 (2 H, d, 3JHH = 7.8
Hz, CH), 8.17 (2 H, d, 3JHH = 8.1 Hz, CH)
18d
30
137 9.6
2.36 (3 H, s, CH3), 3.73 (3 H, d, 3JPH = 13.2 Hz, OCH3), 7.50 (1 H, d, 1JPH = 595 Hz, PH), 7.3–7.6 (8
(d, 1JPH = 595 Hz), H, m, CH), 7.85 (2 H, d, 3JHH = 6.9 Hz, CH), 9.77 (1 H, s, NH)
CHCl3
19ad 45
19be 58
19ce 67
164 79.6, CHCl3
2.43 (3 H, s, CH3), 3.72 (6 H, d, 3JPH = 14.4 Hz, OCH3), 7.2–7.5 (5 H, m, CH), 7.54 (3 H, m, CH),
7.88 (2 H, d, 3JHH = 7.8 Hz, CH), 9.84 (1 H, s, NH)
183 79.1, CHCl3
170 79.8, CHCl3
2.36 (3 H, s, CH3), 3.60 (6 H, d, 3JPH = 14.0 Hz, OCH3), 7.33 (1 H, t, 3JHH = 7.5 Hz, CH), 7.43 (2 H,
t, 3JHH = 7.5 Hz, CH), 7.54 (4 H, m, CH), 7.90 (2 H, d, 3JHH = 7.5 Hz, CH), 10.38 (1 H, s, NH)
2.40 (3 H, s, CH3), 3.65 (6 H, d, 3JPH = 14.1 Hz, OCH3), 3.73 (3 H, s, OCH3), 3.82 (6 H, s, OCH3),
7.22 (2 H, s, CH), 7.39 (1 H, t, 3JHH = 7.5 Hz, CH), 7.48 (2 H, t, 3JHH = 7.5 Hz, CH), 7.55 (2 H, d,
3JHH = 7.5 Hz, CH), 10.25 (1 H, s, NH)
20ad 45
20bd 40
21ae 48
158– 72, dioxane
159
2.31 (3 H, s, CH3), 7.43 (3 H, m, CH), 7.54 (6 H, m, CH), 7.95 (4 H, m, CH), 8.14 (2 H, m, CH)
186– 72, CHCl3
187
2.30 (3 H, s, CH3), 7.40 (2 H, d, 3JHH = 8.1 Hz, CH), 7.47–7.56 (6 H, m, CH), 7.85–8.0 (4 H, m, CH),
8.08 (2 H, d, 3JHH = 8.4 Hz, CH)
197– 72, CHCl3
198
2.15 (3 H, s, CH3), 3.00 [6 H, s, N(CH3)2], 6.82 (2 H, d, 3JHH = 8.1 Hz, CH), 7.46 (1 H, t, 3JHH = 7.5
Hz, CH), 7.52–7.64 (5 H, m, CH), 7.69 (2 H, dd, 3JHH = 8.1 Hz, 3JPH = 14.4 Hz, CH), 7.98 (2 H, d,
3JHH = 7.8 Hz, CH), 8.04 (2 H, d, 3JHH = 7.8 Hz, CH)
21be 41
228 72, CHCl3
2.15 (3 H, s, CH3), 3.00 [6 H, s, N(CH3)2], 6.82 (2 H, d, 3JHH = 8.7 Hz, CH), 7.46 (1 H, t, 3JHH = 7.5
Hz, CH), 7.58–7.62 (4 H, m, CH), 7.69 (2 H, dd, 3JHH = 8.7, 3JPH = 15 Hz, CH), 7.96 (2 H, d,
3JHH = 7.8 Hz, CH), 8.04 (2 H, d, 3JHH = 8.4 Hz, CH)
23e
30
233 14.5, (CH3)2CO
2.17 (3 H, s, CH3), 2.29 (3 H, s, CH3), 6.90 (1 H, m, CH), 7.05 (1 H, d, 3JHH = 6.5 Hz, CH), 7.16 (1
H, s, CH), 7.3–7.6 (11 H, m, CH), 7.68 (2 H, m, CH), 7.77 (2 H, m, CH), 8.27 (1 H, d, 3JPNH = 11.4
Hz, NH), 10.14 (1 H, s, NH)
26eg 32
271– 10, CHCl3
272
2.18 (3 H, s, CH3), 6.53 (2 H, m, CH), 6.72 (1 H, t, 3JHH = 6.9 Hz, CH), 6.78 (2 H, d, 3JHH = 7.5 Hz,
CH), 7.0 (4 H, m, CH), 7.09–7.26 (7 H, m, CH), 7.39 (5 H, m, CH), 7.75 (2 H, dd, 3JHH = 7.8,
3JPH = 7.8 Hz, CH), 7.82 (1 H, br s, NH), 7.86 (2 H, d, 3JHH = 7.5 Hz, CH), 9.6 (1 H, s, NH)
28aad 70
28bbe 40
28ccd 65
160 11, CHCl3
178 10, CHCl3
2.55 (3 H, s, CH3), 3.24 (4 H, m, NCH2), 3.68 (4 H, m, OCH2), 7.39 (1 H, t, 3JHH = 7.5 Hz, CH), 7.4–
7.6 (5 H, m, CH), 7.94 (2 H, d, 3JHH = 7.1 Hz, CH), 8.17 (2 H, d, 3JHH = 7.5 Hz, CH)
1.92 (4 H, m, CH2), 2.50 (3 H, s, CH3), 3.64 (4 H, m, NCH2), 7.43 (3 H, m, CH), 7.53 (2 H, t,
3JHH = 7.5 Hz, CH), 7.9 (2 H, d, 3JHH = 7.1 Hz, CH), 8.1 (2 H, d, 3JHH = 7.8 Hz, CH)
163– 10, CHCl3
164
1.08 [6 H, t, 3JHH = 6.9 Hz, N(CH2CH3)2] 2.40 (3 H, s, CH3), 3.05 [4 H, dq, N(CH2CH3)2], 3.79 (3
H, s, OCH3), 3.87 (6 H, s, OCH3), 7.39 (2 H, s, CH), 7.41 (1 H, t, 3JHH = 7.5 Hz, CH), 7.6 (2 H, t,
3JHH = 7.5 Hz, CH), 8.02 (2 H, d, 3JHH = 7.5 Hz, CH)
30d
31d
54
53
133– 15.9, CHCl3
135
2.29 (3 H, s, CH3), 3.26 (3 H, d, 3JPH = 16.8 Hz, POCH3), 7.16 (5 H, m, CH), 11.69 (1 H, br s, NH)
oilh
20.5, CHCl3
2.24 (3 H, s, CH3), 3.74 (3 H, d, 2.83 (3 H, d, 3JPH = 18.0 Hz, POCH3), 5.21 (2 H, br s, NH2), 7.40 (1
H, m, CH), 7.51 (4 H, m, CH)
a Satisfactory microanalysis obtained: N 0.21; P 0.13.
b Yields refer to pure isolated products.
c Melting points are uncorrected.
d CDCl3.
e DMSO-d6.
f C6D6.
g Spectra was recorded at 50 °C.
h Bp 185 °C / 0.02 mm Hg.
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

912
D. M. Volochnyuk et al.
PAPER
Table 2 13C NMR Data of Phosphorus Compounds 3a, 10b, 28aa, 13aa, 19a, 19b and 26; , J (Hz)
N
CH3 C3 or
C=X
C4a or C7 or
C7a or C1
C4
C2
C3
C4
C1
C2
C3
C4
Other Signals
C5
C3
3aa 13.2 153.7
(2JCP
142.7
147.7
99.4
138.0 123.0 128.6 127.2 131.6 128.8 129.9 132.4 -
(2JCP
(2JCP
(1JCP
= 18.0) = 7.8) = 19.7) = 41.3)
10ba 13.8 155.7
(2JCP
147
148.7
95.1
138.2 123.2 128.9 127.3 129.4 129.0 130.0 139.2 45.2 (NCH2), 67.3 (OCH2)
(2JCP
(1JCP
(3JCP
= 15.0)
= 3.8) = 166.0)
= 5.4)
28aaa 14.2 156.9
(2JCP
148.7
151.0
93.1
138.3 123.3 128.7 127.4 130.7 128.8 128.9 132.9 44.1 (NCH2), 67.3 (3JCP = 7.6,
(2JCP
(2JCP
(1JCP
(3JCP
OCH2)
= 12.8) = 8.5) = 16.2) = 200.6)
= 5.4)
13aaa 14.3 167.1
140.7
(2JCP
150.4
103.1 138.8 123.6 128.0 127.7 132.4 128.5 129.1 132.5 44.2 (NCH2), 66.8 (OCH2),
(1JCP
118.7 (3JCP = 6.8, o-CNHPh),
= 16.7)
= 159.6)
123.9 (m-CNHPh), 122.2 (p-CN-
HPh), 139.5 (ipso-CNHPh
)
19ab 14.9 167.3
19bb 14.9 166.3
26b,c 14.1 158.2
140.7
150.8
107.4 138.5 124.5 128.9 128.5 133.8 128.4 129.4 132.4 53.0 (OCH3)
(2JCP
(2JCP
(1JCP
= 22.1) = 10.3) = 179.3)
140.6
150.8
107.2 138.3 124.4 129.0 128.5 132.3 130.2 129.4 137.9 53.0 (OCH3)
(2JCP
(2JCP
(1JCP
= 23.1) = 9.5) = 178.6)
150.9
(2JCP
151.2
98.5
138.6 122.7 127.2 126.1 133.8 128.6 127.6 129.6 117.5 (3JCP = 7, o-CPNHPh),
128.6 (m-CPNHPh), 120.0
(1JCP
= 23.1)
= 153.9)
(p-CPNHPh), 142.1 (ipso-CPN-
HPh), 131.3 (2JCP = 10.6, o-CP-
Ph), 128.1 (3JCP = 12.8, m-
CPPh), 131.0 (4JCP = 2.5, p-CP-
Ph), 134.8 (1JCP = 131.5, ipso-
CPPh), 121.3 (o-CCNHPh), 128.6
(m-CCNHPh), 123.7 (p-CCNHPh),
139.8 (ipso-CCNHPh
)
a CDCl3.
b DMSO-d6.
c Spectra were recorded at 50 °C.
1
corded on a Varian VXR-300 spectrometer: H and 13C (300 and
75.4 MHz, respectively), CDCl3 and DMSO-d6 as solvents with
TMS as an internal standard; 31P (121 MHz) with 85% H3PO4 as an
external standard. IR-spectra were recorded on an UR-20 spectrom-
eter for samples in KBr discs. Mass-spectra were obtained on a HP
GC/MS 5890/5972 instrument (EI, 70 eV). Starting N-acylami-
nopyrazoles 1 were prepared from corresponding aminopyrazoles
and acyl chlorides or TFAA in pyridine medium.20 p-N,N-Dimeth-
ylaminophenyldichlorophosphine was prepared from N,N-dimethy-
laniline and PCl3 in pyridine medium.21
Finally, we synthesized a novel heterocyclic system: pyra-
zolo[4,3-c][1,5,2]oxazaphosphinine and based on which a
convenient preparative method for the synthesis of deriv-
atives of (5-amino-4-pyrazolyl) phosphonic acid has been
developed. This method permits the introduction of a
wide range of substituents both at the phosphorus, and the
5-amino group of the pyrazole ring. Moreover, the princi-
pal possibility of using TFA protecting group under phos-
phorylation of aminoderivatives of electron-rich aromatic
and heteroaromatic systems at the ortho-position to the
amino group with 1,1-bielectrophilic phosphorus(III) ha-
lides has been shown.
1-Bromo-7-methyl-3,5-diphenyl-1,5-dihydropyrazolo[4,3-
c][1,5,2]oxazaphosphinine (3a)
To a stirred soln of 1a (4.00 g. 14.4 mmol) and Et3N (6.00 mL, 43.3
mmol) in anhyd dioxane (100 mL), PBr3 (1.37 mL, 14.4 mmol) was
added. After 24 h precipitate of Et3N HBr formed was filtered off.
The solvents were evaporated in vacuo to 60 mL, cooled to r.t., hex-
All procedures with hydrolysis and oxidation sensitive compounds
were carried out under an atmosphere of anhyd argon. All solvents
were purified and dried by standard methods. NMR spectra were re-
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of (5-Aminopyrazol-4-yl)-phosphonic Acid Derivatives
913
ane (20 mL) was added and the mixture was refluxed for 5 min. Liq-
uid was decanted under an atmosphere of anhyd argon and the
above procedure was repeated. The light-yellow crystalline precip-
itate formed was dried in vacuo.
1-Methoxy-7-methyl-3,5-diphenyl-1 5-1,5-dihydropyrazolo-
[4,3-c][1,5,2]oxazaphosphinine-1-thioxide (16a) and 7-Methyl-
1-phenoxy-3,5-diphenyl-1 5-1,5-dihydropyrazolo[4,3-
c][1,5,2]oxazaphosphinine-1-thioxide (16ab); Typical Proce-
dure
1-Bromo-7-methyl-5-phenyl-3-trifluoromethyl-1,5-dihydropy-
razolo[4,3-c][1,5,2]oxazaphosphinine (3e)
To a stirred soln of bromoanhydride 3 in pyridine equimolar
amounts of alcohol or phenol and elemental sulfur were added. Af-
ter complete dissolution of the sulfur, pyridine was evaporated in
vacuo. The residue was triturated with H2O and crystallized from 2-
propanol.
To a stirred soln of 1e (3.2 g. 14 mmol) and Et3N (4.16 mL, 30
mmol) in anhyd dioxane (25 mL) at 0 °C, PBr3 (1.33 mL, 14 mmol)
was added and the reaction mixture was allowed to warm to r.t. Af-
ter 15 h, precipitate of Et3N HBr formed was filtered and dioxane
was evaporated in vacuo. The residue was crystallized from pen-
tane.
Methyl(3-methyl-1-phenyl-5-phenylcarboxamido-1H-4-pyra-
zolyl)phosphonite (18)
To a stirred soln of bromoanhydride 3a (1g, 2.6 mmol) in pyridine
(15 mL) anhyd MeOH (0.35 mL, 10.4 mmol) was added. After 15
min, the reaction mixture was added to a stirred ice H2O (80 mL).
The crystalline precipitate formed was filtered.
3-Aryl-1-bromo-7-methyl-5-phenyl-1,5-dihydropyrazolo[4,3-
c][1,5,2]oxazaphosphinine (3); Typical Procedure for One-Pot
Transformations
To a stirred soln of 1 (1.5 mmol) in anhyd pyridine (20 mL), PBr3
(0.14 mL, 1.5 mmol) was added. After 5 min, the reaction mixture
can be used for further transformations.
Dimethyl(3-methyl-1-phenyl-5-arylcarboxamido-1H-4-pyra-
zolyl)thiophosphonates (19);Typical Procedure
To a stirred soln of bromoanhydride 3 (2.6 mmol) in pyridine, an-
hyd MeOH (0.35 mL, 10.4 mmol) and elemental sulfur (83 mg, 2.6
mmol) were added. After complete dissolution of the sulfur, pyri-
dine was evaporated in vacuo. The residue was triturated with H2O
and crystallized from 2-propanol.
7-Methyl-1,3,5-triphenyl-1,5-dihydropyrazolo[4,3-c][1,5,2]ox-
azaphosphinine (4a)
Compound 4a was prepared from 1a and PhPBr2 using the above
procedure for 3a.
19a
3-Methyl-1-phenyl-5-phenylcarboxamido-1H-4-pyrazolylphos-
phinic Acid (6)
The crystals of 3a (500 mg, 1.47 mmol) were ground to a powder
and kept in a thin layer on air within 24 h. The powder was triturated
with ice H2O (2 mL), filtered and dried in vacuo.
EI MS: m/z (%) = 401 (26) [M+], 369 (2.9) [M+ – S], 353 (22)
[M+ – S – CH4], 105 (100) [PhCO+], 93 (8.6), 77 (55) [C6H5 ].
+
1-Aryl-5-Aryl -7-methyl-5-phenyl-1 5-1,5-dihydropyrazolo-
[4,3-c][1,5,2]oxazaphosphinine-1-thioxide (20 and 21); Typical
Procedure
To a stirred soln of 1 (3.6 mmol) in pyridine (20 mL) was added an
equimolar amount of aryldiclorophosphine. After 30 h, elemental
sulfur (120 mg, 3.6 mmol) was added. After full dissolution of the
sulfur, pyridine was evaporated in vacuo. The residue was triturated
with H2O and crystallized from 2-propanol
Phenyl(3-methyl-1-phenyl-5-phenylcarboxamido-1H-4-pyra-
zolyl)phosphinoxide (7)
The crystals of 4a (500 mg, 1.25 mmol) were ground to a powder
and were kept in a thin layer on air within 24 h. The powder was
crystallized from 2-propyl alcohol.
1-Amido-3-aryl-7-methyl-5-phenyl-1 5-1,5-dihydropyrazo-
lo[4,3-c][1,5,2]oxazaphosphinine-1-thioxide (10, 11)
Typical procedure: To a stirred soln of bromoanhydride 3 in pyri-
dine, equimolar amounts of amine and elemental sulfur were added.
After complete dissolution of the sulfur, pyridine was evaporated in
vacuo. The residue was triturated with H2O and crystallized from 2-
propanol.
3-Chloro-4-methylanilido(3-methyl-1-phenyl-5-phenylcarbox-
amido-1H-4-pyrazolyl)(phenyl)phosphinate (23)
To a stirred soln of 4a (1g, 2.6 mmol) in toluene (20 mL) was added
3-chloro-4-methylphenylazide (440 mg, 2.6 mmol). The reaction
mixture was refluxed for 4 h. Toluene was evaporated in vacuo and
the residue was crystallized from 2-propanol.
10b
1-Chloro-7-methyl-1,3,5-triphenyl-1,5-dihydropyrazolo[4,3-
c][1,5,2]oxazaphosphinin-1-ium Chloride (24)
EIMS: m/z (%) = 458 (19) [M+], 372 (32) [M+ – N(CH2CH2)2O],
340 (100) [M+ – N(CH2CH2)2O – S], 326 (5.7), 292 (10), 111 (12)
A soln of 4a (4g, 10.4 mmol) in CH2Cl2 (40 mL) was frozen to
–90 °C. To a crystalline mixture was added a soln of chlorine (0.74
g, 10.4 mmol) in CH2Cl2 (20 mL). After warming to r.t., CH2Cl2
was evaporated in vacuo. The residue obtained was used for further
transformation without purification.
[ClC6H4 ], 86 (59) [N(CH2CH2)2O]+, 77 (21) [C6H5 ].
+
+
5-Arylcarboxamido-3-methyl-1-phenyl-1H-4-pyrazolylphos-
phonic Acid Amides (13)
Typical procedure: To a stirred soln of bromoanhydride 3 in pyri-
dine, equimolar amounts of secondary amine and arylazide were
added. The mixture was maintained at 50 °C until the nitrogen evo-
lution had stopped, and then pyridine was evaporated in vacuo. The
residue was triturated with H2O and crystallized from 2-propyl al-
cohol.
5-(1-Chloro-1-phenylmethylideneamino)-3-methyl-1-phenyl-
1H-4-pyrazolyl(phenyl)chlorophosphinate (25)
Chlorophosphinium chloride 24 was maintained 4 h at 90 °C and
compound 25 formed was used for further transformation without
purification.
1-Methoxy-7-methyl-5-phenyl-3-trifluoromethyl-1,5-dihydro-
pyrazolo[4,3-c][1,5,2]oxazaphosphinine (15ea)
Anilido-5-(1-anilino-1-phenylmethylideneamino)-3-methyl-1-
phenyl-1H-4-pyrazolyl(phenyl)phosphinate (26)
To a stirred soln of bromoanhydride 3e (1.2 g, 3.2 mmol) in Et2O at
–30 °C was added a mixture of MeOH (0.1 mL, 3.2 mmol) and Et3N
(0.55 mL, 4 mmol). After warming to r.t., the precipitate of
Et3N HBr formed was filtered off and Et2O was evaporated in vac-
uo. The residue was crystallized from pentane at –10 °C.
To a stirring soln of 25 (4.7 g, 10.4 mmol) in CH2Cl2 (30 mL),
aniline (3.9 g, 41.6 mmol) was added. The soln was maintained at
45 °C for 4 h. CH2Cl2 was evaporated in vacuo. The residue was
triturated with hot H2O and crystallized from EtOH.
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York

914
D. M. Volochnyuk et al.
PAPER
1-Amido-3-aryl-7-methyl-5-phenyl-1 5-1,5-dihydropyrazolo-
[4,3-c][1,5,2]oxazaphosphinine-1-oxide (28)
(4) Schallner, O.; Gehring, R.; Klauke, E.; Stetter, J.;
Wroblowsky, H. J.; Schmidt, R. R.; Santel, H. J. DE Patent
3402308, 1985; Chem. Abstr. 1986, 104, 34075.
(5) Tolmachev, A. A.; Konovets, A. I.; Kostyuk, A. N.; Pinchuk,
A. M. Top. Heterocycl. Systems 1996, 1, 239; and references
cited therein.
Typical procedure: To a stirred soln of bromoanhydride 3 in pyri-
dine an equimolar amount of secondary amine followed by an
equimolar amount of bromine dissolved in pyridine (5mL) were
added. The stirred reaction mixture was allowed to cooled to r.t. and
five-fold excess of H2O was added. Pyridine was evaporated in vac-
uo and the residue was triturated with H2O.
(6) Oshovsky, G. V.; Pinchuk, A. M.; Tolmachev, A. A.
Mendeleev Commun. 1999, 9, 161–162.
(7) Tolmachev, A. A.; Pushechnikov, A. O.; Krotko, D. G.;
Ivonin, S. P.; Kostyuk, A. N. Khim. Geterosikl. Soedin 1998,
1275.
3-Methyl-1-phenyl-5-trifluoromethycarboxamido-1H-4-pyra-
zolylphosphonic Acid Dimethyl Ester (30)
Ester 15ea (0.96 g, 3 mmol) was dissolved in MeOH (5 mL) at
–40 °C and a soln of 80% H2O2 (0.2 mL) in MeOH (4 mL) was add-
ed. After warming to r.t., MeOH was evaporated in vacuo at 20 °C.
The residue was washed with H2O, dried and crystallized from Et2O
at –20 °C.
(8) Tolmachev, A. A.; Dovgopoly, S. I.; Kostyuk, A. N.;
Kozlov, E. S.; Pushechnikov, A. O.; Holzer, W. Heteroat.
Chem. 1999, 10, 391–398.
(9) Kovalyeva, S. A.; Chubaruk, N. G.; Tolmachev, A. A.;
Pinchuk, A. M. Khim. Geterosikl. Soedin 2001, 1287.
(10) Pinchuk, A. M.; Kovalyova, S. A.; Ivonin, S. P.; Merkulov,
A. S.; Kuanhyda, T. N.; Chaikovskaya, A. A.; Tolmachev,
A. A. Heteroat. Chem. 2001, 12, 641–651.
5-Amino-3-methyl-1-phenyl-1H-4-pyrazolylphosphonic Acid
Dimethyl Ester (31)
To a soln of amide 30 (0.77 g, 2.3 mmol) in MeOH (6 mL), H2O (3
mL) and NH2NH2 H2O (1.5 mL) were added. After 20 h solvent was
evaporated in vacuo at 20 °C. The residue was extracted with Et2O
and distilled in vacuo to give yellow-light oil.
(11) Tolmachev, A. A.; Oshovsky, G. V.; Merkulov, A. S.;
Pinchuk, A. M. Khim. Geterosikl. Soedin 1996, 1288.
(12) (a) Kawanobe, W.; Yamaguchi, K.; Nakahama, S.;
Yamazaki, N. Macromol. Chem. 1985, 186, 1803.
(b) Sinitsa, A. D.; Malenko, D. M.; Repina, L. A.;
Loktionova, R. A.; Shurubura, A. K. Zh. Obshch. Khim.
1986, 56, 1262; Chem. Abstr. 1987, 106: 50311.
(13) Pushechnikov, A. O.; Krotko, D. G.; Volochnyuk, D. M.;
Tolmachev, A. A. Synlett 2001, 860.
Crystal Data for 10a
C21H21N4O2PS, M = 425.5, orthorhombic, space group Pbca,
a = 7.995(6), b = 19.783(9), c = 26.310(9) Å, V = 4161.6 Å3,
Z = 8, dcalcd = 1.36 g cm –3
,
= 2.48 cm–1, F(000) = 1777.9, crystal
size 0.25 0.31 0.65 mm. All data were collected using CuK ra-
diation ( = 0.71069 Å) on a Enraf–Nonius CAD4 diffractometer,
max = 70 °, 293 K, 3396 reflections collected (2729 independent).
An empirical absorption correction based on azimuthal scan data22
was applied. The structure was solved by direct methods and refined
by full-matrix least-squares technique in the anisotropic approxima-
tion using the CRYSTALS23 program package. All hydrogen atoms
were located in the different Fourier maps and included in the final
refinement with fixed positional and thermal parameters. Conver-
gence was obtained at R = 0.062 and Rw = 0.068, GOF = 1.160
(1797 reflections with I > 3 (I), 262 refined parameters; obs/vari-
abl. 6.9, difference electron density 0.52 and –0.46 e/Å3, Chebushev
weighting scheme24 with parameters 1.59, 1.32, and 1.07 was used
in the refinement. Atomic coordinates, bond lengths, bond angles
and thermal parameters have been deposited at the Cambridge Crys-
tallographic Data Centre (CCDC). Any request to the CCDC for
data should quote the full literature citation and the reference num-
ber CCDC 202041.
(14) Malenko, D. M.; Nesterova, L. I.; Luk’yanenko, S. N.;
Sinitsa, A. D. Zh. Obshch. Khim. 1989, 59, 1908; Chem.
Abstr. 1990, 112: 77379.
(15) (a) Kirsanov, A. V.; Shevchenko, V. I. Zh. Obshch. Khim.
1954, 24, 474; Chem. Abstr. 1955, 49, 6164a.
(b) Kabachnik, M. I.; Gilyarov, V. A. Izv. Akad. Nauk. 1956,
790; Chem. Abstr. 1957, 51: 1823b.
(16) Petrov, K. I.; Nifant’ev, E. E.; Sopikova, I. I. Dokl. Akad.
Nauk. 1963, 151, 859; Chem. Abstr. 1963, 59: 12627g.
(17) Sasse, K. In Methoden der Organichen Chemie (Houben–
Weyl), Vol. XII/2; Mueller, E., Ed.; Georg Thieme Verlag:
Stuttgart, 1964, 284.
(18) (a) Ben-Ishai, D.; Altman, J.; Peled, N. Tetrahedron 1977,
33, 2715. (b) Khorana, H. G.; Turner, A. F.; Vizsolyi, J. P. J.
Am. Chem. Soc 1961, 83, 686.
(19) (a) Quick, J.; Meltz, C. J. Org. Chem 1979, 44, 573.
(b) Schwartz, M. A.; Rose, B. F.; Vishnuvajjala, B. J. Am.
Chem. Soc 1973, 95, 612.
(20) Moeller, F. In Houben–Weyl (Methoden Organishen
Chemie); Vol. XI/2: Mueller E.; Thieme: Stuttgart, 1958, 4th
ed., 11.
References
(21) Tolmachev, A. A.; Ivonin, S. P.; Kharchenko, A. V.; Kozlov,
E. S. Zh. Obshch. Khim. 1989, 59, 1193; Chem. Abstr, 1990,
112: 77350.
(22) North, A. C. T.; Phillips, D. C.; Mathews, F. S. Acta
Crystallogr., Sect. A 1968, 24, 351.
(23) Watkin, D. J.; Prout, C. K.; Carruthers, J. R.; Betteridge, P.
W. In Crystals, 10; Oxford University Press: Oxford, 1996.
(24) Carrythers, J. R.; Watkin, D. J. Acta Crystallogr., Sect. A
1979, 35, 698.
(1) Kost, A. N.; Grandberg, I. I. Adv. Heterocycl. Chem. 1966,
6, 347–429.
(2) (a) Elguero, J. In Pyrazoles and their Benzo Derivatives
,Comprehensive Heterocyclic Chemistry, Vol. 5; Katritzky,
A. R.; Rees, C. W., Eds.; Pergamon: Oxford, 1984, 167–30.
(b) Elguero, J. In Pyrazoles ,Comprehensive Heterocyclic
Chemistry, Vol. 2; Katritzky, A. R.; Rees, C. W.; Scriven, E.
F., Eds.; Pergamon: Oxford, 1996, 1–75.
(3) (a) Grapov, A. F. Usp. Khim. 1999, 68, 773; and references
cited therein. (b) Cole, L. M.; Nicholson, R. A.; Casida, J. E.
Pestic. Biochem. Physiol. 1993, 46, 47–54.
Synthesis 2003, No. 6, 906–914 ISSN 0039-7881 © Thieme Stuttgart · New York