Synthesis of 1-arylcyclopropylphosphonates

Article abstract of DOI:10.1007/s11172-007-0290-y

A simple method for the synthesis of 1-arylcyclopropylphosphonates was proposed. The method involves treatment of 1-arylethenylphosphonic acids or their esters with diazomethane followed by thermolysis of intermediate 3-aryl-4,5-dihydro-3H-pyrazol-3-ylphosphonates.

Full text of DOI:10.1007/s11172-007-0290-y

Russian Chemical Bulletin, International Edition, Vol. 56, No. 9, pp. 1884—1890, September, 2007
1884
Synthesis of 1ꢀarylcyclopropylphosphonates*
N. S. Gulyukina, A. V. Varakuta, and I. P. Beletskayaꢀ
Department of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 939 3618. Eꢀmail: beletska@org.chem.msu.ru
A simple method for the synthesis of 1ꢀarylcyclopropylphosphonates was proposed. The
method involves treatment of 1ꢀarylethenylphosphonic acids or their esters with diazomethane
followed by thermolysis of intermediate 3ꢀarylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonates.
Key words: cyclopropylphosphonates, 4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonates, vinylꢀ
phosphonates, diazomethane, [2+3] cycloaddition, organophosphorus compounds.
Interest in cyclopropylphosphonates and cyclopropylꢀ
of the cyclopropane fragment to restrict the skeleton conꢀ
formationally. For instance, cyclopropyl analogs of
Dꢀ2ꢀaminoꢀ5ꢀphosphonopentanoic acid (NMDA antagoꢀ
nist),1 3ꢀaminoꢀ2ꢀ(4ꢀchlorophenyl)propylphosphonic
acid (GABAB antagonist Phaclophen),30,32,35 and the
nucleotide (E)ꢀ9ꢀ(4ꢀphosphonobutꢀ3ꢀenyl)adenine31,43
exhibiting antiretroviral activity have been obtained.
In this context, the synthesis of 1ꢀarylcyclopropylꢀ
phosphonates, which are conformationally constrained
analogs of 1ꢀarylethylphosphonic acids, are of interest.
The latter are phosphorus analogs of 2ꢀarylpropionic acids
(a wellꢀknown class of nonsteroidal antiinflammatory and
analgesic drugs such as naproxen and ibuprofen) and exꢀ
hibit negative inotropic,46 Ca2+ꢀantagonistic,46,47 neuroꢀ
protective,47 and psychotropic activities,47 inhibit cycloꢀ
oxygenase,48 and serve as haptens of reactive immunizaꢀ
tion.49,50 Here we studied the cyclopropanation of 1ꢀarylꢀ
ethenylphosphonic acids51 with diazomethane as the simꢀ
plest synthetic route to 1ꢀarylcyclopropylphosphonates.
phosphonic acids is due to their known biological activiꢀ
ties. For instance, some compounds of this class have
been found to be antagonists for the NMDA receptor,1
inhibitors of alanine racemase and aminocyclopropaneꢀ
carboxylate deaminase,2 and insectoacaricides.3
Several approaches to the design of the cyclopropane
ring in cyclopropylphosphonates have been documented.
This is mostly done via reactions of olefins with diazoꢀ
phosphonate.1,4—17 Reactions of vinylphosphonate with
diazo compounds are employed in substantially fewer
studies.18—25 In both cases, the reaction is carried out in
both the presence1,7—17,25 and in the absence of a cataꢀ
lyst.4,5,18—24
Other methods include reactions of vinylphosphonates
with Fischer carbene complexes,26,27 dihalocarbenes,3,28
or sulfur ylides;24,29—32 nucleophilic addition of substiꢀ
tuted αꢀhalomethylphosphonate anions to the Michael
acceptors followed by intramolecular SN2 cyclizaꢀ
tion;33—39 intramolecular cyclization of alkylphosphonate
anions containing a leaving group in the γꢀposition;2,40—44
Lewis acidꢀpromoted [2+1] cycloaddition of 1ꢀselenoꢀ2ꢀ
silylethene to 1ꢀ(methoxycarbonyl)vinylphosphonates.45
The proposed synthetic routes lead to a sufficiently
broad variety of structures. When choosing target molꢀ
ecules with potential biological activity, two basic prinꢀ
ciples are guided. First, phosphorus analogs of cycloꢀ
propanecarboxylic acids with already known activity
are intensively synthesized. For instance, Pꢀanalogs of
( )ꢀ(Z )ꢀN,Nꢀdiethylꢀ2ꢀaminomethylꢀ1ꢀphenylcycloꢀ
propanecarboxamide (antidepressant Minalcipran),38
chrysanthemic acid,9 and (–)ꢀalloꢀnorcoronamic acid44
have been obtained.
Results and Discussion
A reaction of diethyl 1ꢀphenylethenylphosphonate (1a)
with diazomethane (2 equiv.) in ether for 3 h gave diethyl
3ꢀphenylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonate (2a)
as the sole product (Scheme 1). In the 31P NMR specꢀ
Scheme 1
According to the other approach, known biologically
active acyclic phosphonates are modified by introduction
* Dedicated to Academician G. A. Abakumov on the occasion
of his 70th birthday.
Reagents and conditions: CH2N2, Et2O, 20 °C, 3 h; ~100% yield.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1820—1826, September, 2007.
1066ꢀ5285/07/5609ꢀ1884 © 2007 Springer Science+Business Media, Inc.

1ꢀArylcyclopropylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 9, September, 2007
1885
trum of the reaction mixture, the signal of the starting
compound 1a at δP 17.7 disappears; instead, a new signal
appears at δP 19.8.
bands in the range characteristic of ν(N—H) and ν(C=N)
(usually, 1595—1635 cm–1).19,20,53 The 13C (Table 1) and
1H NMR spectra (Table 2) of product 2a show two sets of
signals for the diastereotopic ethoxy groups. The 13C NMR
spectrum exhibits a characteristic doublet at δC 98.02
(1JCP = 148.0 Hz) for the quaternary C atom. Four comꢀ
plex multiplets correspond to the protons of the fiveꢀ
membered heterocycle. The two lowꢀfield multiplets
(δH 4.58 and 4.79) probably relate to the strongly coupled
CH2N protons, while the two highꢀfield multiplets
(δH 1.84 and 2.67) relate to the CH2CP protons. The
considerable difference in the chemical shifts of the latter
is due to the vicinity of the asymmetric center.
The structure of product 2a isolated in quantitative
yield was proved by elemental analysis and spectroscopic
methods. The IR spectrum exhibits a characteristic set of
bands corresponding to the diethoxyphosphoryl fragment:
a band at 1260 cm–1 (P=O stretching vibrations), a broad
band at 980 cm–1 (C—C stretch), and two very strong
bands at 1030 and 1060 cm–1 (O—C stretch).52 The
stretching vibrations of the endocyclic N=N bond give
rise to a weak band at 1560 cm–1. 4,5ꢀDihydroꢀ3Hꢀ
pyrazolꢀ3ꢀylphosphonates can undergo prototropic isoꢀ
merization into 4,5ꢀdihydroꢀ1Hꢀpyrazolꢀ5ꢀylphosphonꢀ
ates.8,19,20,53 However, this is not the case with product 2a
because its IR spectrum contains no intense absorption
Treatment of 1ꢀarylethenylphosphonic acids (1b—f)
with diazomethane (4—5 equiv.) gave the corresponding
dimethyl 3ꢀarylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonꢀ
Table 1. 13C NMR spectra of 3ꢀarylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonates 2a—f
Comꢀ
pound
R
Ar
13C NMR (CDCl3), δ (J/Hz)
P(O)(OR)2
Pyrazoline ring
Ar*
CH2CP CH2N
CP
2a
2b
2c
2d
СH2Me
Me
15.89 (Me); 15.94 (Me); 27.34
62.86 (d, 2JC,P = 7.7,
CH2); 63.66 (d,
77.36
77.65
77.85
77.43
98.02 (d,
126.93 (d, C(2), C(6),
1JC,P = 148.0) 3JC,P = 4.6); 127.55 (C(4));
128.04 (C(3), C(5));
2
2JC,P = 6.9, CH2)
137.55 (d, C(1), JC,P = 4.6)
53.75 (d, 2JC,P = 7.6);
54.55 (d, 2JC,P = 7.6)
27.60
27.56
27.36
98.22 (d,
127.15 (d, C(2), C(6),
1JC,P = 147.5) 3JC,P = 4.2); 128.01 (C(4));
128.50 (C(3), C(5)); 137.56
2
(d, C(1), JC,P = 5.1)
Me
53.85 (d, 2JC,P = 5.9);
54.51 (d, 2JC,P = 7.6)
97.78 (d,
128.50 (d, C(2), C(6),
1JC,P = 148.4) 3JC,P = 4.2); 128.66
(C(3), C(5)); 134.05 (C(4));
2
136.13 (d, C(1), JC,P = 6.7)
Me
53.48 (d, 2JC,P = 7.7);
54.40 (d, 2JC,P = 6.9)
97.85 (d,
22.08 (Me); 29.88 (CH);
1JC,P = 147.2) 44.73 (CH2); 126.69 (d,
3
C(2), C(6), JC,P = 3.8);
129.04 (C(3), C(5));
2
134.49 (d, C(1), JC,P = 5.4);
141.38 (C(4))
2e
Me
Me
53.69 (d, 2JC,P = 6.9);
54.43 (d, 2JC,P = 6.9)
27.43
27.70
77.60
77.66
98.00 (d,
126.82, 126.99 (C(2), C(6),
1JC,P = 148.0) C(2´), C(6´)); 127.36 (C(4´));
127.43 (d, C(3), C(5),
3JC,P = 4.6); 128.63 (C(3′),
C(5´)); 136.38 (d, C(4),
2JC,P = 6.1); 140.06, 140.65
(C(1), C(1´))
2f
53.76 (d,2JC,P = 6.9);
54.56 (d, 2JC,P = 6.9)
98.24 (d,
124.92 (C(3)); 126.04 (d, C(1),
1JC,P = 148.0) 3JC,P = 6.9); 126.35, 126.39,
127.49, 128.18 (2С) (C(4),
C(5), C(6), C(7), C(8));
132.66, 132.87 (C(8a), C(8b));
2
134.91 (d, C(2), JC,P = 5.4)
* The signals for the C atoms of the aromatic ring were assigned with consideration for known54 substituent increments.

1886
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 9, September, 2007
Gulyukina et al.
1
Table 2. H and 31P NMR spectra (CDCl3) of 3ꢀarylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonates 2a—f
Comꢀ
pound
1H NMR, δ (J/Hz)
31P NMR
δ
P(O)(OR)2
Pyrazoline ring
Ar*
CH2CP
CH2N
(m, 1 H) (m, 1 H)
2a
1.16 (t, 3 H, Me, 3JH,H = 7.1);
1.26 (t, 3 H, Me, 3JH,H = 7.0);
3.84 (m, 1 H, CH2); 3.95 (m, 1 H,
CH2); 4.07 (m, 2 H, CH2)
3.58 (d, 3 H, 3JP,H = 10.6);
3.70 (d, 3 H, 3JP,H = 10.7)
3.62 (d, 3 H, 3JP,H = 10.7);
3.74 (d, 3 H, 3JP,H = 10.7)
1.84,
2.67
4.58,
4.79
7.30 (m, 1 H, H(4)); 7.38 (t, 2 H, H(3),
H(5), 3JH,H = 7.2); 7.69 (m, 2 H,
H(2), H(6))
19.8
2b
2c
1.87,
2.67
1.80,
2.66
4.61,
4.80
4.61,
4.83
7.33 (m, 1 H, H(4)); 7.40 (m, 2 H, H(3),
H(5)); 7.69 (m, 2 H, H(2), H(6))
22.1
21.6
7.38 (d, 2 H, H(3), H(5), 3JАВ = 8.7);
3
7.63 (dd, 2 H, H(2), H(6), JАВ = 8.7,
4JHP = 2.4)
2d
2e
2f
3.56 (d, 3 Н, 3JP,H = 10.5);
3.71 (d, 3 Н, 3JP,H = 10.7)
1.86,
2.63
4.59,
4.77
0.89 (d, 6 H, СН3, 3JH,H = 6.6); 1.86 (m, 1 H,
СH); 2.47 (d, 2 H, СН2, 3JH,H 7.1); 7.17 (d,
2 H, H(3), H(5), 3JАВ = 8.1); 7.59 (dd, 2 H,
H(2), H(6), 3JАВ = 8.1, 4JHР = 2.1)
7.36 (m, 1 H, H(4´)); 7.45 (m, 2 H, H(3´),
H(5´)); 7.60 (m, 2 H, H(2´), H(6´)); 7.64 (d,
2 H, H(2), H(6), 3JАВ = 8.5); 7.76 (dd, 2 H,
H(3), H(5), 3JАВ = 8.5, 3JP,H = 2.3)
7.47—7.51 (m, 2 H); 7.79—7.90
22.3
22.1
21.9
3.64 (d, 3 H, 3JP,H = 10.6);
3.76 (d, 3 H, 3JP,H = 10.7)
1.91,
2.69
4.64,
4.83
3.56 (d, 3 H, 3JP,H = 10.6);
3.75 (d, 3 H, 3JP,H = 10.7)
1.96,
2.74
4.65,
4.81
(m, 4 H); 8.14 (br.s, 1 H, H(1))
* The signals for the protons of the aromatic ring were assigned with consideration for known54 substituent increments.
Scheme 3
ates (2b—f) (Scheme 2) also isolated in quantitative yields.
Their compositions and structures were confirmed by elꢀ
emental analysis and spectroscopic methods (see Experiꢀ
mental and Tables 1, 2).
Scheme 2
Ar = Ph (b), 4ꢀClC6H4 (c), 4ꢀBuiC6H4 (d), 4ꢀPhC6H4 (e),
2ꢀnaphthyl (f)
Reagents and conditions: CH2N2, Et2O, 20 °C, 3 h; ~100% yield.
Reagents and conditions: ∆, 1 h, oꢀxylene.
Photolysis4,5,19,20,24 or thermolysis18,20 of 4,5ꢀdihydroꢀ
3Hꢀpyrazolꢀ3ꢀylphosphonates produces cyclopropylꢀ
phosphonates through liberation of nitrogen. Compound
2a was quantitatively decomposed in boiling oꢀxylene
over 1 h (Scheme 3). The 31P NMR spectrum of the
reaction mixture shows, along with a signal at δP 28.7 for
diethyl 1ꢀphenylcyclopropylphosphonate (3a), signals at
δP 18.3 and 17.0 assigned to byꢀproducts: Eꢀ and Zꢀisoꢀ
mers of diethyl 1ꢀphenylpropꢀ1ꢀenylphosphonate (the inꢀ
tegral intensity ratio is 88 : 4 : 8).
The 1H NMR spectrum contains signals for the
3
3
Zꢀisomer at δH 6.54 (dq, Holefin, JH,H = 7.3 Hz, JP,H
48.4 Hz) and 2.25 (dd, Hallylic, JH,H = 7.3 Hz, JP,H
=
=
3
4
3.5 Hz) and signals for the Eꢀisomer at δH 6.98 (dq,
3
3
Holefin, JH,H = 6.9 Hz, JP,H = 23.1 Hz) and 1.73 (dd,
Hallylic,
3JH,H = 6.9 Hz, JP,H = 3.3 Hz). Note that
4
the thermolysis of 4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosꢀ
phonates sometimes leads only to acyclic unsaturated
products.22

1ꢀArylcyclopropylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 9, September, 2007
1887
In boiling toluene, compound 2a decomposed slowly
(after 1 h, its conversion was 57%); the selectivity of the
process was virtually unchanged.
We failed to separate the reaction mixture by distillaꢀ
tion; for this reason, unsaturated byꢀproducts were reꢀ
moved by treatment with a solution of KMnO4 in aqueous
acetone. Subsequent distillation gave the analytically and
spectroscopically pure target product 3a in 78% preparaꢀ
tive yield.
propane ring are manifested as two complex multiplets at
δH 1.06 and 1.49. The signals in the H NMR spectra
1
(see Table 4) were assigned by comparing the coupling
constants JH,P with consideration for the known19,54
3
3
ratio JHCCPꢀcis > JHCCPꢀtrans. The 31P chemical shift is
δP 28.7 (see Table 4). This value falls in the range deꢀ
scribed for cyclopropylphosphonates (δP 21—36).19,20,24,25
The absence of the pronounced anisotropic effect of
the αꢀaromatic substituent is probably associated with
a larger bond angle between the exocyclic bonds in
cyclopropanes compared to a tetrahedral bond configuꢀ
ration.
The IR spectrum of cyclopropylphosphonate 3a reꢀ
tains the set of bands of the diethoxyphosphoryl fragment.
The band at 1230 cm–1 is due to the breathing vibrations
of the cyclopropane ring and bands at 840 and 940 cm–1
correspond to the deformation vibrations (see Ref. 52).
In the 13C (Table 3) and 1H NMR spectra (Table 4), one
set of signals corresponds to equivalent ethoxy groups.
The quaternary C atom is manifested as a doublet at
A number of dimethyl 1ꢀarylcyclopropylphosphonates
(3b—f) were obtained and characterized analogously (see
Tables 3, 4 and Experimental).
In conclusion, roomꢀtemperature reactions of 1ꢀarylꢀ
ethenylphosphonic acids or their esters with diazomethane
are regiospecific: [2+3] cycloaddition gives 3ꢀarylꢀ4,5ꢀ
dihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonates. Thermolysis of
the latter leads mainly to 1ꢀarylcyclopropylphosphonates
isolated in 53—79% yields (with respect to the twoꢀstep
1
δC 21.12. The coupling constant JC,P = 191.7 Hz is
higher than that for compound 2a in agreement with
1
a known54 increase in JC,P for the C atom with a
greater sꢀorbital contribution. The protons of the cycloꢀ
Table 3. 13C NMR spectra of 1ꢀarylcyclopropylphosphonates 3a—f
Comꢀ
pound
R
Ar
13C NMR (CDCl3), δ (J/Hz)
P(O)(OR)2
Threeꢀmembered ring
Ar*
CH2
CP
3а
3b
3c
СH2Me
Me
16.24 (d, Me, 3JC,P = 6.1); 11.34
62.15 (d, CH2, 2JC,P =6.9)
21.12 (d,
127.09 (C(4)); 128.02 (C(3), C(5));
130.97 (C(2), C(6)); 138.62 (C(1))
1JC,P = 191.7)
52.90 (d, 2JC,P = 6.8)
53.01 (d, 2JC,P = 6.7)
11.14
11.28
20.38 (d,
1JC,P = 191.4)
127.17 (C(4)); 128.10 (C(3), C(5));
130.80 (C(2), C(6)); 138.29 (C(1))
Me
19.96 (d,
1JC,P = 191.4)
128.31 (C(3), C(5)); 132.14 (d,
3
C(2), C(6), JC,P = 3.0); 133.08
(C(4)); 136.96 (C(1))
3d
Me
52.95 (d, 2JC,P = 6.9)
11.21
20.01 (d,
1JC,P = 189.4)
22.26 (Me); 29.99 (CH); 44.94
(CH2); 128.88 (C(3), C(5)); 130.50
(d, C(2), C(6), 3JC,P = 3.8); 135.44
(C(1)); 140.70 (C(4))
3e
3f
Me
Me
53.11 (d, 2JC,P = 6.8)
53.03 (d, 2JC,P = 6.1)
11.37
11.37
20.18 (d,
126.97 (4 С); 127.26 (C(4´)); 128.68
(2 C); 131.26 (C(3), C(5)); 137.44,
140.20, 140.56 (C(1), C(1´), C(4))
1JC,P = 190.5)
20.66 (d,
1JC,P = 191.7)
125.93, 126.02, 127.46, 127.60,
127.75, 128.70, 129.72 (d,
2JC,P = 4.6); 132.48, 133.05 (C(8a),
C(8b)); 135.84 (C(2))
* The signals for the C atoms of the aromatic ring were assigned with consideration for known54 substituent increments.

1888
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 9, September, 2007
Gulyukina et al.
Table 4. 1H and 31P NMR spectra (CDCl3) of 1ꢀarylcyclopropylphosphonates 3a—f
Comꢀ
pound
1H NMR, δ (J/Hz)
Threeꢀmembered ring
transꢀHCCP cisꢀHCCP
31P NMR
δ
P(O)(OR)2
Ar*
(m, 2 H)
(m, 2 H)
3а
1.25 (t, 6 H, Me,
3JH,H = 7.1); 4.04
(m, 4 H, CH2)
3.68 (d, 6 H,
1.06
1.49
7.23 (m, 1 H, H(4)); 7.29 (m, 2 H, H(3),
H(5)); 7.42 (m, 2 H, H(2), H(6))
28.7
(3JH,P = 10.4)
(3JH,P = 16.4)
3b
3c
3d
1.07
(3JH,P = 10.5)
1.04
1.50
(3JH,P = 16.4)
1.50
7.23 (m, 1 H, H(4)); 7.29 (m, 2 H, H(3),
H(5)); 7.41 (m, 2 H, H(2), H(6))
31.4
30.8
31.8
3JH,P = 10.6)
3.70 (d, 6 H,
7.26 (d, 2 H, H(3), H(5), 3JAB = 8.6); 7.35
(dd, 2 H, H(2), H(6), 3JAB = 8.6, 4JHP = 2.0)
0.89 (d, 6 H, Me, 3JH,H = 6.6); 1.84 (m, 1 H,
CH); 2.44 (d, 2 H, CH2, 3JH,H = 7.2); 7.07
(d, 2 H, H(3), H(5), 3JAB = 8.0); 7.31 (dd,
2 H, H(2), H(6), 3JAB = 8.0, 4JHP = 2.0)
7.34 (m, 1 H, H(4´)); 7.43 (m,
3JH,P = 10.6)
3.68 (d, 6 H,
3JH,P = 10.6)
(3JH,P = 10.4)
1.06
(3JH,P = 16.3)
1.48
(3JH,P = 10.5)
(3JH,P = 16.3)
3e
3f
3.73 (d, 6 H,
3JH,P = 10.6)
1.12
(3JH,P = 10.4)
1.54
(3JH,P = 16.3)
31.5
31.4
2 H, H(3´), H(5´); 7.48 (dd, 2 H, H(3), H(5),
3JAB = 8.2, 4JH,P = 1.3); 7.53 (d, 2 H, H(2),
H(6), 3JAB = 8.2); 7.57 (m, 2 H, H(2´), H(6´))
3
3.71 (d, 6 H,
3JH,P = 10.5)
1.18
(3JH,P = 10.4)
1.58
(3JH,P = 16.4)
7.43—7.49 (m, 2 Н); 7.56 (d, 1 H, JH,H = 8.5);
7.77—7.81 (m, 3 H); 7.84 (br.s, 1 H, H(1))
* The signals for the protons of the aromatic ring were assigned with consideration for known54 substituent increments.
Scheme 4
an Electrothermal 9100 melting point apparatus in sealed capilꢀ
laries.
Diethyl ether and oꢀxylene were dehydrated in a standard
way. The starting diethyl 1ꢀphenylethenylphosphonate (1a) and
1ꢀarylethenylphosphonic acids (1b—f) were prepared as described
earlier.51 A solution of diazomethane in ether was prepared acꢀ
cording to a standard procedure.55
Diethyl 3ꢀphenylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonate
(2a). A roundꢀbottom flask fitted with a magnetic stirring bar,
a dropping funnel, and a drying tube packed with calcium chloꢀ
ride was charged with phosphonate 1a (1.718 g, 7.15 mmol) and
anhydrous diethyl ether (5 mL). A 0.11 M solution of diazoꢀ
methane (127 mL, 14 mmol, 2 equiv.) in anhydrous ether was
added dropwise with stirring for 30 min and the solution was
stirred for an additional 3 h. Volatile components were removed
first in a rotary evaporator and then under high vacuum.
Phosphonate 2a as a pale yellow oil was obtained in quantitative
yield. Found (%): C, 55.30; H, 6.56; N, 9.84. C13H19N2O3P.
Calculated (%): C, 55.31; H, 6.78; N, 9.92. IR (thin film),
ν/cm–1: 1560 (N=N); 1260 (P=O); 1060 (O—C); 1030 (O—C);
980 (OC—C).
Conditions: ∆, oꢀxylene.
2, 3
Ar
Yield (%)
From 31P NMR
Preparative
b
c
d
e
f
Ph
86
86
90
89
88
53
68
56
79
66
4ꢀClC6H4
4ꢀBuiC6H4
4ꢀPhC6H4
2ꢀnaphthyl
process). Isomeric 1ꢀarylpropꢀ1ꢀenylphosphonates are
detected as byꢀproducts.
Dimethyl 3ꢀphenylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosphonate
(2b) was obtained analogously in quantitative yield from
1ꢀphenylethenylphosphonic acid (1b) (1.291 g, 7.01 mmol) and
0.08 M diazomethane (350 mL, 28 mmol, 4 equiv.). White crysꢀ
tals turned yellow in air, m.p. 74—75 °C. Found (%): C, 52.14;
H, 5.87; N, 11.08. C11H15N2O3P. Calculated (%): C, 51.97;
H, 5.95; N, 11.02. IR (Nujol), ν/cm–1: 1555 (N=N); 1255
(P=O); 1070 (O—C); 1030 (O—C).
Dimethyl 3ꢀ(4ꢀchlorophenyl)ꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀ
ylphosphonate (2c) was obtained analogously in quantitative yield
from 1ꢀ(4ꢀchlorophenyl)ethenylphosphonic acid (1c) (2.000 g,
9.15 mmol) and 0.11 M diazomethane (325 mL, 36 mmol,
Experimental
1
H, 31P, and 13C NMR spectra were recorded on a Bruker
Avanceꢀ400 spectrometer (400, 162, and 101 MHz, respectively).
1H chemical shifts are referenced to SiMe4 as the internal stanꢀ
dard; 31P chemical shifts are referenced to 85% H3PO4 as the
external standard; 13C chemical shifts are referenced to CDCl3
(δ 77.0). IR spectra were recorded on a Carl Zeiss URꢀ20 specꢀ
trophotometer. Elemental analysis was carried out on a Carlo
Erba automatic analyzer. Melting points were measured with

1ꢀArylcyclopropylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 9, September, 2007
1889
4 equiv.). Creamꢀcolored crystals, m.p. 82—83 °C. Found (%):
C, 46.06; H, 5.05; N, 9.47. C11H14ClN2O3P. Calculated (%):
C, 45.77; H, 4.89; N, 9.70. IR (Nujol), ν/cm–1: 1560 (N=N);
1250 (P=O); 1070 (O—C); 1040 (O—C).
Dimethyl 3ꢀ(4ꢀisobutylphenyl)ꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀ
ylphosphonate (2d) was obtained analogously in quantitative yield
from 1ꢀ(4ꢀisobutylphenyl)ethenylphosphonic acid (1d) (1.882 g,
7.83 mmol) and 0.1 M diazomethane (400 mL, 40 mmol,
5 equiv.). A pale yellow oil. Found (%): C, 58.37; H, 7.58;
N, 9.79. C15H23N2O3P. Calculated (%): C, 58.06; H, 7.47;
N, 9.03. IR (thin film), ν/cm–1: 1555 (N=N); 1260 (P=O);
1060 (O—C); 1020 (O—C).
Dimethyl 3ꢀ(biphenylꢀ4ꢀyl)ꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylꢀ
phosphonate (2e) was obtained analogously in quantitative yield
from 1ꢀ(biphenylꢀ4ꢀyl)ethenylphosphonic acid (1e) (1.575 g,
6.05 mmol) and 0.17 M diazomethane (144 mL, 24 mmol,
4 equiv.). Pale yellow crystals, m.p. 81—82 °C. Found (%):
C, 61.88; H, 5.96; N, 8.59. C17H19N2O3P. Calculated (%):
C, 61.81; H, 5.80; N, 8.48. IR (thin film), ν/cm–1: 1560 (N=N);
1260 (P=O); 1065 (O—C); 1040 (O—C).
IR (thin film), ν/cm–1: 1270 (P=O); 1230 (cyclopropane); 1070
(O—C); 1040 (O—C); 935 (cyclopropane); 860 (cyclopropane).
Dimethyl 1ꢀ(4ꢀisobutylphenyl)cyclopropylphosphonate (3d)
was obtained analogously from compound 2d (2.431 g,
7.83 mmol) in boiling anhydrous oꢀxylene (165 mL). The yield
was 1.229 g (56%), a nearly colorless transparent oil, b.p.
155—160 °C (2 Torr). Found (%): C, 63.72; H, 8.35. C15H23O3P.
Calculated (%): C, 63.82; H, 8.21. IR (thin film), ν/cm–1: 1265
(P=O); 1230 (cyclopropane); 1070 (O—C); 1040 (O—C); 935
(cyclopropane); 835 (cyclopropane).
Dimethyl 1ꢀ(biphenylꢀ4ꢀyl)cyclopropylphosphonate (3e) was
obtained analogously from compound 2e (1.978 g, 5.99 mmol)
in boiling anhydrous oꢀxylene (100 mL). The product was exꢀ
tracted with toluene (3×50 mL). The solvent was removed under
reduced pressure and the residue was kept in high vacuum. The
yield of compound 3e was 1.426 g (79%), creamꢀcolored crysꢀ
tals, m.p. 56—57 °C. Found (%): C, 67.47; H, 6.52. C17H19O3P.
Calculated (%): C, 67.54; H, 6.34. IR (Nujol), ν/cm–1: 1260
(P=O); 1225 (cyclopropane); 1070 (O—C); 1040 (O—C); 940
(cyclopropane); 865 (cyclopropane).
Dimethyl 3ꢀ(2ꢀnaphthyl)ꢀ4,5ꢀdihydroꢀ3Hꢀpyrazolꢀ3ꢀylphosꢀ
phonate (2f) was obtained analogously in quantitative yield from
1ꢀ(2ꢀnaphthyl)ethenylphosphonic acid (1f) (1.906 g, 8.14 mmol)
and 0.15 M diazomethane (220 mL, 33 mmol, 4 equiv.). A pale
yellow oil. Found (%): C, 58.98; H, 5.82; N, 9.08. C15H17N2O3P.
Calculated (%): C, 59.21; H, 5.63; N, 9.21. IR (thin
film), ν/cm–1: 1555 (N=N); 1250 (P=O); 1050 (O—C);
1030 (O—C).
Diethyl 1ꢀphenylcyclopropylphosphonate (3a). A solution of
compound 2a (2.019 g, 7.15 mmol) in anhydrous oꢀxylene
(160 mL) was refluxed for 3 h. The solvent was thoroughly
removed under reduced pressure. The residue was dissolved in
acetone (10 mL) and a saturated solution of KMnO4 (50 mL) in
aqueous acetone (1 : 5) was added dropwise with stirring for 7 h.
The excess of KMnO4 was decomposed by adding saturated
aqueous Na2SO3 until the violet color vanished. The brown
precipitate that formed was filtered off and washed with acꢀ
etone. The combined filtrates were concentrated and the prodꢀ
uct was extracted with diethyl ether (3×20 mL). The organic
extracts were dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The residue was distilled in vacuo under
dry argon. The yield of compound 3a was 1.416 g (78%), a nearly
colorless transparent oil, b.p. 140—150 °C (2 Torr). Found (%):
C, 61.68; H, 7.48. C13H19O3P. Calculated (%): C, 61.41; H, 7.53.
IR (thin film), ν/cm–1: 1260 (P=O); 1230 (cyclopropane); 1070
(O—C); 1040 (O—C); 970 (OC—C); 940 (cyclopropane); 840
(cyclopropane).
Dimethyl 1ꢀ(2ꢀnaphthyl)cyclopropylphosphonate (3f) was obꢀ
tained analogously from compound 2f (2.477 g, 8.14 mmol) in
boiling anhydrous oꢀxylene (165 mL). The yield was 1.487 g
(66%), a light yellow oil, b.p. 170 °C (0.1 Torr). Found (%):
C, 65.13; H, 6.39. C15H17O3P. Calculated (%): C, 65.21; H, 6.20.
IR (thin film), ν/cm–1: 1265 (P=O); 1225 (cyclopropane); 1070
(O—C); 1040 (O—C); 940 (cyclopropane); 835 (cyclopropane).
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos 05ꢀ03ꢀ
33013 and 04ꢀ03ꢀ39017ꢀGFEN) and the INTAS (Project
No. 05ꢀ1000008ꢀ8064).
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Received May 30, 2007;
in revised form July 12, 2007