Addition of tris(trimethylsilyl)phosphite to N-formyl derivatives of five-membered nitrogen heterocycles

Full text of DOI:10.1134/S1070363216110268

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 11, pp. 2558–2561. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.A. Prishchenko, R.S. Alekseev, M.V. Livantsov, O.P. Novikova, L.I. Livantsova, V.I. Terenin, V.S. Petrosyan, 2016, published in
Zhurnal Obshchei Khimii, 2016, Vol. 86, No. 11, pp. 1919–1922.
LETTERS
TO THE EDITOR
Addition of Tris(trimethylsilyl)phosphite
to N-Formyl Derivatives of Five-Membered Nitrogen Heterocycles
A. A. Prishchenko*, R. S. Alekseev, M. V. Livantsov,
O. P. Novikova, L. I. Livantsova, V. I. Terenin, and V. S. Petrosyan
Lomonosov Moscow State University, Moscow, 119991 Russia
*
e-mail: aprishchenko@yandex.ru
Received June 23, 2016
Keywords: tris(trimethylsilyl)phosphite, five-membered nitrogen heterocycles, N-formyl derivatives
DOI: 10.1134/S1070363216110268
Functionalized phosphonic and methylenediphos-
phonic acids and derivatives thereof with fragments of
nitrogen heterocycles are well known hydroxy(amino)-
acids biomimetics and natural pyrophosphates. Some
of them, like zoledronic, and minodronic and risedro-
nic acids, are widely used in medicine, as well as are
of interest as effective ligands [1, 2]. We have pre-
viously developed convenient methods for the syn-
thesis of aminomethylenediphosphorus-containing acids
and their derivatives using phosphorous acid trimethyl-
silyl esters as highly reactive synthons [3, 4]. Here we
studied addition of tris(trimethylsilyl) phosphite to
easily accessible N-formyl derivatives of five-mem-
bered nitrogen heterocycles with two or three nitrogen
atoms prepared in situ by the known methods [5] using
formic acid and sym-dicyclohexylcarbodiimide.
conditions and led to the formation of functionalized
phosphonates 1 and diphosphonates 2 in various ratios
depending on the structure of the starting heterocycle.
Thus, in the case of 3,5-dimethyl-1H-pyrazole phos-
phonate 1b was formed mainly, while diphosphonate
2a was obtained in a high yield when using imidazole
(Scheme 1).
Trimethylsilyl esters 1 and 2 reacted readily with an
excess of methanol under mild conditions to form
functionalized mono- or diphosphonic acids 3 and 4,
respectively (Scheme 2).
The resulting compound 1–4 can be used for the
synthesis of new organophosphorus compounds,
including both heterocyclic and phosphonic fragments.
In addition, they are precursors of highly promising
drugs and effective polydentate ligands for mono- and
diphosphorus-containing complexes of various metals.
The reactions proceeded only in the presence of
trimethylsilyl triflate as a catalyst (cf. [4]) in mild
Scheme 1.
HCOOH, (c-C H N=) C
P(OSiMe ) , CF SO SiMe
3 3 3 3 3
6
11
2
HetNH
HetNCHO
HetNCHP(O)(OSiMe3)2
OSiMe3
−
(c-C H NH) CO
6
11
2
1
а−1d
P(OSiMe ) , CF SO SiMe
3
3
3
3
3
1
HetNC H[P(O)(OSiMe ) ]
3
2 2
−
(Me Si) O
3
2
2а−2d
N
N
N
N
N
HetN =
(а),
(b),
N (c),
N (d).
N
N
2
558

ADDITION OF TRIS(TRIMETHYLSILYL)PHOSPHITE
2559
Scheme 2.
3
MeOH
1
1
а−1d −3MeOSiMe3
HetNC HP(O)(OH)2
OH
3
а−3d
4
MeOH
1
2а−2d
HetNC H[P(O)(OH) ]
2 2
−
4MeOSiMe3
4а−4d
N
N
N
N
N
HetN =
(а),
(b),
N (c),
N (d).
N
N
O,O-Bis(trimethylsilyl)-1H-imidazol-1-yl- (trimethyl-
siloxy)methylphosphonate (1a) and O,O,O,O-tetra
O,O-Bis(trimethylsilyl)-1H-benzimidazol-1-yl-
(trimethylsiloxy)methylphosphonate (1b). Yield
30%, bp 110°C (1 mmHg). H NMR spectrum, δ, ppm:
1
(
trimethylsilyl)-1H-imidazol-1-yl-methylenediphos-
phonate (2a). A solution of 14.4 g (0.07 mol) of sym-
dicyclohexylcarbodiimide in 20 mL of methylene
chloride was added with stirring to a mixture of 3.4 g
–0.44 s (9H, Me Si), –0.25 s (18H, Me Si), 5.58 d (1H,
3
3
1
2
13
C H, J = 4.4 Hz), 6.70–7.45 m (5H, CHHet).
C
PH
NMR spectrum, δ , ppm: –0.22 (Me Si), 1.11 (Me Si),
C
3
3
1
1
(
0.05 mol) of imidazole and 2.8 g (0.06 mol) of formic
75.50 d (C , J = 214.1 Hz), 110.40 (C ), 120.23
PC Het
acid in 50 mL methylene chloride. The mixture was
stirred for 6 h and then kept for 12 h. The precipitate
was filtered off. To the filtrate were added 44.8 g
(C ), 122.51 (C ), 123.19 (C ), 139.62 (C ),
Het Het Het Het
3
1
143.28 (C ), 145.74 (C ). P NMR spectrum: δP
Het
Het
–3.47 ppm. Found, %: C 45.81; H 7.40. C H N O PSi .
17
33
2
4
3
(
0.15 mol) of tris(trimethylsilyl) phosphite and a
Calculated, %: C 45.92; H 7.48.
solution of 2.9 g (0.013 mol) of trimethylsilyl triflate
in 10 mL of methylene chloride. The mixture was
heated on a boiling water bath until complete distilla-
tion of low-boiling compounds, then distilled to yield
O,O,O,O-Tetra(trimethylsilyl)-1H-benzimidazol-
-ylmethylenediphosphonate (2b). Yield 62%, bp
39°C (1 mmHg). H NMR spectrum, δ, ppm: –0.38 s
1
1
1
and –0.31 s (18H, Me Si), –0.16 s (18H, Me Si), 3.55 t
3
3
1
.8 g (9%) of phosphonate 1a (bp 102°C, 1 mmHg)
and 22.0 g (83%) of diphosphonate 2a (bp 126°C,
mmHg).
1
2
(
1H, C H, J = 16.8 Hz), 6.65–7.55 m (5H, CHAr).
C NMR spectrum, δ , ppm: 1.10 (Me Si), 68.11 d
PH
13
C
3
1
1
1
(
C , J = 167.3 Hz), 112.46 (C ), 119.92 (C ),
PC Het Het
1
Phosphonate 1a. H NMR spectrum, δ, ppm: –0.38
s (9H, Me SiO), –0.24 s (18H, Me Si), 5.22 d (1H,
122.13 (C ), 122.75 (C ), 139.71 (C ), 141.75
Het Het Het
3
1
(C ), 145.46 (C ).
P
NMR spectrum: δP
3
3
Het
Het
1
2
13
C H, J = 4.8 Hz), 6.57 s (2H ), 7.15 s (1H ). C
–0.58 ppm. Found, %: C 41.26; H 7.20. C H N O P Si .
PH
Het
Het
20 42 2 6 2 4
NMR spectrum, δ , ppm: 1.62 (Me Si), –0.25 and 0.05
Calculated, %: C 41.36; H 7.29.
C
3
1
1
(
1
Me Si), 76.47 d (C , J = 213.2 Hz), 106.61 (C ),
39.80 (C ), 146.52 (C ). P NMR spectrum: δP
Het Het
3 PC Het
O,O-Bis(trimethylsilyl)-3,5-dimethyl-1H-pyrazol-
-yl(trimethylsiloxy)methylphosphonate (1c). Yield
6%, bp 106°C (1 mmHg). H NMR spectrum, δ, ppm:
3
1
1
8
–
–
4.02 ppm. Found, %: C 39.42. H 7.83. C H N O PSi .
1
13
31
2
4
3
Calculated, %: C 39.57; H 7.92.
0.38 s and –0.31 s (18H, Me Si), –0.16 s (9H, Me Si),
3
3
1
Diphosphonate 2а. H NMR spectrum, δ, ppm:
1.71 s and 1.99 s (6H, Ме), 5.36 s (1H, CH ), 5.40 d
Het
1
2
13
–
0.15 s (18H, Me Si), –0.14 s (18H, Me Si), 3.55 t
(1H, C H, J = 7.2 Hz). C NMR spectrum, δ , ppm:
PH C
3
3
1
2
(
1H, C H, J = 17.2 Hz), 6.57 s (2H ), 7.15 s (1H ).
–1.62 (Me Si), –0.25 and 0.05 (Me Si), 10.77 and
PH
Het
Het
3
3
1
3
1
1
C NMR spectrum, δ , ppm: 0.47 (Me Si), 67.80 t
12.36 (Ме), 81.19 d (C , J = 214.1 Hz), 106.61
C
3
PC
1
1
31
31
(
C , J = 168.2 Hz), 121.00 (C ), 134.69 (C ). P
(C ), 139.80 (C ), 146.52 (C ). P NMR spec-
PC
Het
Het
Het
Het
Het
NMR spectrum: δ –0.32 ppm. Found, %: C 36.12; H
trum: δ –3.35 ppm. Found, %: C 42.49; H 8.28.
P
P
7
.52. C H N O P Si . Calculated, %: C 36.21; H 7.60.
C H N O PSi . Calculated, %: C 42.62; H 8.35.
16
40
2
6
2
4
15 35
2
4
3
Phosphonates 1b–1d and diphosphonates 2b–2d
were prepared similarly.
O,O,O,O-Tetra(trimethylsilyl)-3,5-dimethyl-1H-
pyrazol-1-ylmethylenediphosphonate (2c). Yield
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 11 2016

2
560
PRISHCHENKO et al.
1
13
7
–
(
%, bp 129°C (1 mmHg). H NMR spectrum, δ, ppm:
0.12 s and –0.16 s (36H, Me Si), 1.80 s and 2.01 s
6.57 s (2H ), 7.92 s (1H ). C NMR spectrum, δ ,
Het Het C
1
1
ppm: 78.81 d (C , J = 180.4 Hz), 117.96 (CHet),
132.86 (C ). P NMR spectrum: δ 7.47 ppm. Found,
3
PC
1
2
31
6H, Ме), 3.58 t (1H, C H, J = 17.2 Hz), 5.36 s (1H,
PH
Het
P
1
3
CH ). C NMR spectrum, δ , ppm: 0.35 (Me Si),
0.80 and 12.40 (6H, Ме), 68.09 t (C , J = 168.2
Hz), 106.68 (C ), 139.86 (C ), 146.57 (C ).
NMR spectrum: δ –0.30 ppm. Found, %: C 38.52; H
%: C 26.86; H 3.88. C H N O P. Calculated, %: C
Het
C
3
4 7 2 4
1
1
1
26.98; H 3.96.
H-Benzimidazol-1-yl(hydroxy)methylphosphonic
PC
31
P
Het
Het
Het
1
P
1
acid (3b). Yield 94%, mp 157–159°C (decomp.). H
7
7
.86. C H N O P Si . Calculated, %: C 38.69; H
18 44 2 6 2 4
1
2
NMR spectrum, δ, ppm: 5.15 d (1H, C H, J
=
PH
.94.
O,O-Bis(trimethylsilyl)-1H-benzotriazol-1-yl(tri-
methylsiloxy)methylphosphonate (1d). Yield 59%,
bp 108°C (1 mmHg). H NMR spectrum, δ, ppm:
0.36 s (9H, Me Si), –0.05 s (18H, Me Si), 6.26 d (1H,
C H, J = 6.4 Hz), 6.99–7.76 m (4H, C H ).
3
4
6
.4 Hz), 7.17 d.d (2H, CH , J = 16.0, J = 3.2
Het HH HH
3
4
Hz), 7.47 d.d (2H, CHHet, JHH = 16.0, JHH = 3.2 Hz),
1
3
7.57 s (1H, CH ). C NMR spectrum, δ , ppm: 78.85
Het C
1
1 1
d (C , J = 170.0 Hz), 114.16 (C ), 125.86 (C ),
PC Het Het
3
1
–
129.74 (C ), 138.52 (C ). P NMR spectrum: δP
3
3
Het Het
1
2
13
C
6.88 ppm. Found, %: C 41.97; H 3.91. C H N O P.
8 9 2 4
PH
6
4
NMR spectrum, δ , ppm: –0.93 (Me Si), –0.43
Calculated, %: C 42.12; H 3.98.
C
3
1
1
(
Me Si), –0.75 (Me Si), 80.73 d (C , J = 213.2 Hz),
3 3 PC
3,5-Dimethyl-1H-pyrazol-1-yl(hydroxy)methylphos-
1
13.37 (C ), 119.20 (C ), 124.17 (C ), 127.30
Het Het Het
3
1
phonic acid (3c). Yield 97%, mp 357–359°C (decomp.).
(
C ), 131.84 (C ), 146.45 (C ). P NMR spec-
Het Het Het
1
H NMR spectrum, δ, ppm: 1.86 s and 2.20 s (6H,
trum: δ –4.81 ppm. Found, %: C 43.03; H 7.16.
P
1
2
Ме), 4.92 d (1H, C H, J = 6.0 Hz), 5.64 s (1H,
CH ). C NMR spectrum, δ , ppm: 10.47 and 12.44
(Ме), 88.18 d (C , JPC = 191.4 Hz), 103.71 (CHet),
144.05 (CHet). P NMR spectrum: δ 10.42 ppm.
PH
C H N O PSi . Calculated, %: C 43.12; H 7.24.
1
6
32
3
4
3
1
3
Het
C
1
1
O,O,O,O-Tetra(trimethylsilyl)-1H-benzotriazol-1-
ylmethylenediphosphonate (2d). Yield 30%, bp 133°C
3
1
P
1
(
1 mmHg). H NMR spectrum, δ, ppm: –0.11 s (36H,
Found, %: C 34.78; H 5.30. C H N O P. Calculated,
6
11
2
4
1
2
Me Si), 3.75 t (1H, C H, J = 16.8 Hz), 7.17–7.83 m
%: C 34.96; H 5.38.
3
PH
1
3
(
4H, C H ). C NMR spectrum, δ , ppm: 0.01 s (36H,
6 4 C
1
1
1H-Benzotriazol-1-yl(hydroxy)methylphosphonic
acid (3d). Yield 95%, mp 105–107°C (decomp.). H
NMR spectrum, δ, ppm: 6.43 d (1H, C H, J
Me Si), 67.71 t (C , J = 168.2 Hz), 110.50 s (CHet),
3
PC
1
1
14.55 s (C ), 119.44 s (C ), 126.22 s (C ), 129.93
Het Het Het
1
2
3
1
=
=
PH
HH
HH
s (C ), 140.27 s (C ). P NMR spectrum: δP
Het
Het
3
4
7
3
3
.2 Hz), 7.41 d.d (1H, CH , J
= 6.4, J
= 6.4, J
Het
HH
–
0.47 ppm. Found, %: C 39.03; H 7.01. C H N O P Si .
19 41 3 6 2 4
3
4
.2 Hz), 7.89 d.d (2H, CH , J
=
Het
HH
Calculated, %: C 39.22; H 7.10.
1
3
1
.2 Hz). C NMR spectrum, δ , ppm: 79.96 d (C ,
C
1
1
H-Imidazol-1-ylmethylenediphosphonic acid (4a).
A solution of 10.6 g (0.02 mol) of diphosphonate 2a in
5 mL of diethyl ether was added to 40 mL of
JPC = 187.7 Hz), 114.92 (CHet), 118.84 (CHet), 125.42
31
(C ), 126.86 (C ), 131.87 (C ), 145.86 (C ).
P
Het
Het
Het
Het
1
NMR spectrum: δ 10.62 ppm. Found, %: C 36.55; H
P
methanol with cooling to 10°C and stirring. The
mixture was heated at reflux and then the solvent was
distilled off. The resulting white crystals were heated
in a vacuum of 1 mmHg for 1 h. Yield 98% (4.7 g),
3.48. C H N O P. Calculated, %: C 36.70; H 3.52.
7
8
3
4
1
H-Benzimidazol-1-ylmethylenediphosphonic
1
acid (4b). Yield 98%, mp 348–350°C (decomp.). H
1
2
1
NMR spectrum, δ, ppm: 4.18 t (1H, C H, J
=
=
=
PH
mp 174–176°C. H NMR spectrum, δ, ppm: 3.33 t
3
4
1
2
16.0 Hz), 7.18 d.d (1H, CH , J = 6.0 Hz, J
Het
HH
HH
HH
(
1H, C H, J = 16.0 Hz), 6.55 s (2H, CH ), 7.85 s
PH Het
3
4
1
3
1
3.2 Hz), 7.46 d.d (2H, CH , J
= 6.0, J
Het
HH
(
1H, CH ). C NMR spectrum, δ , ppm: 66.26 t (C ,
Het C
JPC = 139.9 Hz), 117.83 (C ), 132.43 (C ).
1
3
1
31
3.2 Hz), 7.56 (1H, CH ). C NMR spectrum, δC,
ppm: 66.86 d (C , J = 142.1 Hz), 113.79 (C ),
25.73 (C ), 129.59 (C ), 138.88 (C ). P NMR
Het
P
Het
Het
1
1
PC
Het
NMR spectrum: δ 14.66 ppm. Found, %: C 19.69; H
P
3
1
1
Het Het Het
3
.28. C H N O P . Calculated, %: C 19.85; H 3.33.
4 8 2 6 2
spectrum: δ 15.63 ppm. Found, %: C 32.74; H 3.40.
P
Acids 3a–3d and 4b–4d were prepared similarly.
H-Imidazol-1-yl(hydroxy)methylphosphonic acid
C
8
H
10
N
2
O
6
P
2
. Calculated, %: C 32.89; H 3.45.
1
3,5-Dimethyl-1H-pyrazol-1-ylmethylenediphos-
1
(
3а). Yield 96%, mp 144–145°C (decomp.). H NMR
phonic acid (4c). Yield 98%, mp 357–359°C (decomp.).
1
2
1
spectrum, δ, ppm: 6.81 d (1H, C H, J = 4.2 Hz),
H NMR spectrum, δ, ppm: 1.82 s and 2.14 s (6H,
PH
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 11 2016

ADDITION OF TRIS(TRIMETHYLSILYL)PHOSPHITE
Ме), 3.97 t (1H, C H, J = 15.6 Hz), 5.60 s (1H,
ACKNOWLEDGMENTS
2561
1
2
PH
1
3
CH ). C NMR spectrum, δ , ppm: 10.44 and 12.34
Het
C
This work was financially supported by the Russian
Foundation for Basic Research (grants nos. 14-03-00001,
1
1
(
Ме), 55.57 t (C , J = 181.7 Hz), 105.63 (CHet),
PC
3
1
1
40.83 (CHet). P NMR spectrum: δ 15.03 ppm.
P
1
5-03-00002).
Found, %: C 26.49; H 4.52. C H N O P . Calculated,
6
12
2
6 2
%: C 26.68; H 4.48.
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H-Benzotriazol-1-ylmethylenediphosphonic acid
1
(
4d). Yield 96%, mp 355–357°C (decomp.). H NMR
spectrum, δ, ppm: 3.88 t (1H, C H, J = 17.2 Hz),
.01 d (1H, CH , J = 8.2 Hz), 8.95 d (1H, CHHet,
1
2
PH
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3
8
Het
13
HH
3
J
= 8.2 Hz). C NMR spectrum, δ , ppm: 65.28 t
HH
1
C
1
(
1
(
2
3
C , J = 150.2 Hz), 113.61 (C ), 118.64 (C ),
PC
Het
Het
24.03 (C ), 125.42 (C ), 126.86 (C ), 138.69
Het Het Het
3
1
C ). P NMR spectrum: δ 16.41 ppm. Found, %: C
Het P
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7 9 3 6 2
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4
(
00 spectrometers from solutions in CDCl (1, 2),
3
CD ) SO, D O or C D N (3, 4), internal reference
3 2 2 5 5
1
13
TMS ( H, C) or external reference 85% H PO in
3
4
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1
D O ( P).
2
1995, no. 5, p. 503. doi 10.1055/s-1995-3959
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 11 2016