Synthesis of new functionalized mono-And bisphosphinates with 2,6-di-tert-butyl-4-methylphenol fragments

Article abstract of DOI:10.1002/hc.20475

Convenient procedures for the synthesis of functionalized mono- and bisphosphinates with 2,6-di-tert-butyl-4-methylphenol (ionol) fragments, starting from the available 3,5-di-tert-butyl-4-benzaldehyde and its derivatives, are proposed, and some propertie

Full text of DOI:10.1002/hc.20475

Heteroatom Chemistry
Volume 19, Number 6, 2008
Synthesis of New Functionalized Mono- and
Bisphosphinates with 2,6-Di-tert-butyl-4-
methylphenol Fragments
Andrey A. Prishchenko, Mikhail V. Livantsov, Olga P. Novikova,
Ludmila I. Livantsova, and Elena R. Milaeva
Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, 119991 Russia
Received 7 April 2008; revised 13 May 2008
cals and were interesting as biological active com-
ABSTRACT: Convenient procedures for the syn-
pounds [2]. In this work, we propose the conve-
thesis of functionalized mono- and bisphosphinates
nient methods for the synthesis of new functional-
with 2,6-di-tert-butyl-4-methylphenol (ionol) frag-
ized mono- and bisphosphinates including of ionol
ments, starting from the available 3,5-di-tert-butyl-
fragments, starting from the readily accessible 3,5-
4-benzaldehyde and its derivatives, are proposed,
di-tert-butyl-4-hydroxybenzaldehyde (A), 3,5-di-tert-
and some properties of the new phosphorus-
butyl-4-hydroxybenzalchloride (B), and 3,5-di-tert-
substituted sterically hindered phenols are presented.
butyl-4-hydroxybenzoyl chloride (C), which were
ꢀ
C
2008 Wiley Periodicals, Inc. Heteroatom Chem 19:562–
prepared by the procedures described in [3–5], and
trimethylsilyl esters of functionalized trivalent phos-
phorus acids which were prepared by us early as
568, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20475
unique organophosphorus synthons [6–8]. In the
present study, we found that the aldehyde A and
its derivatives B and C smoothly react with various
trimethylsilyl esters of trivalent phosphorus acids
under mild conditions to form new functionalized
phosphorus-containing sterically hindered phenols,
which are presented as promising polydentate lig-
ands and effective antioxidants.
INTRODUCTION
Recently we have proposed the convenient proce-
dures for synthesis of a series of organophospho-
rus derivatives of 2,6-di-tert-butyl-4-methylphenol
(ionol) with one, two, or three phosphorus-
containing groups [1]. These compounds were used
by us for the preparation of stable phenoxyl radi-
RESULTS AND DISCUSSION
All starting functionalized phosphonites are de-
scribed in [6–8] except phosphonite 1, which was
specially synthesized in high yield via the addition of
bis(trimethylsiloxy)phosphine to the carbonyl group
of 3-pyridinecarboxaldehyde after the heating of in-
termediate D with bis(trimethylsilyl)amine (Eq. (1);
cf. [7]).
Correspondence to: Andrey A. Prishchenko; e-mail:
aprishchenko@yandex.ru.
Contract grant sponsor: Russian Foundation for Basic
Research.
Contract grant number: 08-03-00282.
2008 Wiley Periodicals, Inc.
c
ꢀ
562

Synthesis of New Functionalized Mono- and Bisphosphinates with 2,6-Di-tert-butyl-4-methylphenol Fragments 563
Me3SiO
PyCHO
(MeSi)2NH
NH3
(Me3SiO)2PCH(OSiMe3)Py
PCH(OSiMe3)Py
(Me3SiO)2PH
H
O
O
D
1
Py =
N
So functionalized bis(trimethylsilyl)phosphonites
readily added by the carbonyl group of aldehyde
A in methylene chloride to give phosphinates 2–4
in high yields (Eq. (2)). Note that under the mild
conditions, the sterically hindered hydroxyl group
of aldehyde A is not trimethylsilylated with excess of
bis(trimethylsilyl) phosphonite (cf. [1]).
esters of trivalent phosphorus acids with read-
ily available 3,5-di-tert-butyl-4-hydroxybenzoyl
chloride C [5] yield new diphosphorylated hy-
droxymethylene derivatives, containing a sterically
hindered phenolic fragment. So trimethylsilyl
phosphites and functionalized trimethylsilyl phos-
phonites taken in excess readily react with acid
X
Ar CHO (A)
(Me3SiO)2PX
Me3SiOP
O
CH(OSiMe3)Ar
(2)
2,3,4
Bu-t
OH X = CH(OSiMe3)
Bu-t
,
(2)
Ar =
, (CH2)2
(3), (CH2)2
N
(4)
N
N
Using functionalized phosphonites, we have de-
vised a convenient method for preparing bisphosphi-
nates, which include trimethylsiloxymethyl groups,
chloride C in methylene chloride to form bispho-
sphonates 8,9 or bisphosphinates 10–13, respec-
tively, in high yields (Eq. (4)).
Ar
Me3SiO
X
2(Me3SiO)2PX
Me3SiCl
[(RO)2P]2CAr
OSiMe3
2(RO)2POSiMe3
Me3SiCl
ArCOCl
P C
OSiMe3
O
O
2
10–13
8,9
C
(4)
Bu-t
OH, R = Et (8), Me3Si (9); X = (CH2)2Ph (10),
Bu-t
(13)
N
(12),
(CH )
(11),
(CH )
N
(CH2)2
2 2
Ar =
2 2
O
N
pyridine moieties, and sterically hindered phenolic
fragments. Thus, trimethylsilyl phosphonites readily
react with benzalchloride B in a methylene chloride
solution by the Arbuzov reaction scheme to form
bisphosphinates 5–7 in high yields (Eq. (3)). In these
cases, too, the sterically hindered phenolic fragment
is preserved (cf. [1]).
Under similar conditions, the reaction of diethyl
trimethylsilyl phosphite or phosphonite 1 with acid
chloride C in 1:1 ratio gives keto phosphonate 14
or keto phosphinate 15 in high yields (Eq. (5)).
Me3SiO
X
ArCHCl2 (B)
−2 Me3SiCl
2 (Me3SiO)2PX
P CHAr
O
2
(3)
5,6,7
Bu-t
OH, X = CH(OSiMe3)
Bu-t
(5)
(7)
N
Ar =
, (CH2)2
(6), (CH2)2
N
N
Various derivatives of substituted hydrox-
ymethylenebisphosphonic acids are good complex-
ones and are widely used in medicine [9–11]. In this
study, we showed that the reactions of trimethylsilyl
Heteroatom Chemistry DOI 10.1002/hc

564 Prishchenko et al.
CH(OSiMe3)
C(O)Ar
15
(EtO)2POSiMe3
Me3SiCl
1
(EtO)2PC(O)Ar
O
C
Me3SiOP
O
N
Me3SiCl
(5)
14
Bu-t
OH
Bu-t
Ar =
Thus, the reaction of excess trimethylsilyl phosphite with acid chloride C involves two steps: the Arbuzov
reaction followed by addition of trimethylsilyl phosphite to the carbonyl group of keto phosphonate 14 to
obtain bisphosphonate 8 (cf. [12]; Eq. (6)).
Ar
(EtO)2POSiMe3
(EtO)2POSiMe3
Me3SiCl
(6)
ArCOCl
(EtO)2PC(O)Ar
[(EtO)2P]2C
OSiMe3
O
O
C
14
8
Bu-t
OH
Ar =
Bu-t
Here we found a facile route to new derivatives of unsymmetrical hydroxymethylenebisphosphorus acids
containing a 2,6-di-tert-butylphenol fragment starting from phosphonate 14. Tris(trimethylsilyl)phosphite
as well as functionalized trimethylsilyl phosphonites taken in excess readily add to the carbonyl group
of keto phosphonate 14 with the formation of bisphosphonate 16 and phosphonate-phosphinates 17,18,
respectively, in high yields (Eq. (7)).
O
O
(Me3SiO)2PX
Ar
(Me3SiO)3P
Ar
(EtO)2P
(EtO)2P
14
C
C
Me3SiO
OSiMe3
OSiMe3
(Me3SiO)2P
O
(7)
P
X
O
16
17,18
Bu-t
,
OH X = (CH2)2Ph (17), (CH2)2COOSiMe3 (18)
Ar =
Bu-t
The reactions of trimethylsilyl esters of organophosphorus acids 2–7 and 9–18 with excess methanol gave
functionalized organophosphorus acids 19–33 in high yields containing PCOH and PCP fragments (Eq. (8)).
X
nMeOH
nMe3SiOMe
HOP
O
2,3,4
5,6,7
CH(OH)Ar
19,20,21
HO
X
nMeOH
nMe3SiOMe
CHAr
2
P
O
22,23,24
(8)
Ar
HO
nMeOH
nMe3SiOMe
C
2
P
9,10,11,12,13
X
OH
O
25,26,27,28,29
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Functionalized Mono- and Bisphosphinates with 2,6-Di-tert-butyl-4-methylphenol Fragments 565
CH(OH)
2MeOH
HOP
15
N
2Me3SiOMe
C(O)Ar
O
30
O
Ar
(EtO)2P
nMeOH
nMe3SiOMe
C
16,17,18
HO
X
OH
P
O
31,32,33
Bu-t
OH, X =CH(OH)
Bu-t
(CH ) Ph (26,32),
(21,24,29), OH (25,31)
N
(CH )
(20,23,28),
(19,22),
(CH2)2
2 2
Ar =
N
N
(CH2)2
N
(27), (CH2)2COOH (33)
2 2
O
to a solution of 30 g of bis(trimethylsiloxy)phosphine
in 60 mL of methylene chloride, and was cooled
to 0◦C. The mixture was stirred for 0.5 h, the
Acids 19–31 are obtained as white hygroscopic crys-
tals, and acids 32,33 are viscous oils. Acids 25–27,31
decompose on heating above 120–130◦C without def-
inite melting points. In contrast, acids 19–24,28,29
are more stable due to pyridine moieties in their
molecules (cf. [12]). Previously unknown hydrox-
ymethylenediphosphoryl compounds containing a
sterically hindered phenolic fragment are promis-
ing complexing agents and antioxidants. Also the
derivatives of substituted unsymmetrical hydrox-
ymethylenediphosphoryl acids containing two phos-
phoryl groups with different extent of polarization
are of interest as unusual ligands and biologically
active compounds. The structures of compounds
solvent was then distilled off, and 20
g of
bis(trimethylsilyl)amine was added to the residue.
The mixture was refluxed until ammonia no longer
evolved and then distilled to obtain 33.9 g of phos-
phonite 1 (see Table 1).
O-Trimethylsilyl[pyrid-3-yl(trimethylsiloxy)-
methyl]3,5-di-tert-butyl-4-hydroxyphenyl-
(trimethylsiloxy)methylphosphinate (2)
3,5-Di-tert-butyl-4-hydroxybenzaldehyde A, 4.7 g,
was added with stirring to a solution of 7.8 g of phos-
phonite 1 in 30 mL of methylene chloride, and was
cooled to 10◦C. The mixture was stirred for 0.5 h, the
solvent was then distilled off, the residue was diluted
with 5 mL of hexane, and the mixture was cooled to
−5◦C. The solvent was removed, and it was kept in
a vacuum (0.5 mmHg) for 1 h to obtain 10.7 g of
phosphinate 2 as a thick oil.
1
1–33 were confirmed by the H, 13C, 31P NMR spec-
tra, which show characteristic signals of the PCHOH
and PCP fragments and signals of substituted aro-
matic fragments (see Table 1). The elemental analy-
sis data of synthesized compounds are summarized
in Table 2.
EXPERIMENTAL
Compounds 3–7 were prepared similarly.
1
The H, 13C, and 31P NMR spectra were registered
on a Bruker Avance-400 spectrometer (400, 100, and
162 MHz, respectively) in CDCl3 (1–18), CD3OD (19–
24,28–30), or (CD3)2SO (25–27,31–33) against TMS
(1H and 13C) and 85% H3PO4 in D2O (31P). All reac-
tions were performed under dry argon in anhydrous
solvents. Aldehyde A, dichloride B, and benzoyl chlo-
ride C were prepared according to the procedures de-
scribed by Coppinger and Campbell [3], Popov et al.
[4], Ivakhnenko et al. [5], respectively.
O,O,O,O-Tetraethyl(3,5-di-tert-butyl-4-hydroxy-
phenyl)trimethylsiloxymethylenebisphosphonate
(8)
A
mixture of 3.8
g
of 3,5-di-tert-butyl-4-
hydroxybenzoic acid, 10 mL hexane, and 8 mL
thionyl chloride was refluxed for 0.5 h, the solvent
was distilled off in a vacuum, and the residue was
kept in a vacuum (0.5 mmHg) for 0.5 h. To a solution
of thus obtained benzoyl chloride C in 15 mL of
methylene chloride, a solution of 8 g of diethyl
trimethylsilyl phosphate in 20 mL of methylene
chloride was added with stirring and was cooled to
10◦C. The mixture was stirred for 0.5 h and heated
to reflux, after which the solvent was distilled off,
O,O-Bis(trimethylsilyl)pyrid-3-yl-
(trimethylsiloxy)methylphosphonite (1)
A solution of 3-pyridinecarboxaldehyde, 10.7 g in
25 mL of methylene chloride was added with stirring
Heteroatom Chemistry DOI 10.1002/hc

566 Prishchenko et al.
TABLE 1 Yields, Products, Constants, and NMR Spectral Data (δ, ppm; J, Hz) of Compounds 1–33a
2
Compound Yield (%) Mp (◦C) δH C1H JPH
δ (C1)
1JPC δ(C1), d JPC δ(C3), s δ(C4), d JPC
δ , s
P
1
2
87
86
118 (1)a 4.13 d
4
10
8
8
6
5
8
5
8
18
12
18
8
16
18
17
18
–
79.56 d
70.71 d
71.89 d
68.99 d
70.67 d
74.64 d
73.93 d
74.78 d
74.10 d
42.31 t
72.36 d
43.31 t
71.91 d
49.80 t
52.34 t
49.82 t
52.40 t
80.57 t
79.82 t
83.07 t
14 134.59
9
148.57b 134.18
4
–
–
–
–
15
13
14
15
–
–
–
–
18
18
17
16
s
s
8
8
s
16
16
18
s
–
–
137.91
30.99
c
oil
4.83 d
5.19 d
4.57 d
4.94 d
4.78 d
4.58 d
4.85 d
4.66 d
3.75 t
4.81 d
3.49 t
4.88 d
3.42 t
3.38 t
3.41 t
3.26 t
–
108
–
–
–
–
90
91
–
–
–
–
–
–
c
c
c
107
110
112
120
117
120
118
78
115
80
113
81
–
–
3
4
5
89
91
89
oil
oil
78
26.22
26.17
21.71
29.22
29.46
160.73
159.28
150.72
150.78
–
41.84
39.94
40.80
38.90
30.93
90 27.39b
21.22
89 27.21b
c
–
–
–
–
–
–
c
c
c
–
–
–
–
–
30.49
6
7
90
88
82
27.47
97
29.18
29.14
28.88
28.00
160.31
160.35
147.00
147.22
37.94
29.23
36.32
36.56
16.16
−0.90
39.16
80
80
78
29.25 106
28.42
28.91
102
84
82
s
8
9
10
91
90
92
127
146
111
152 126.75
161 127.67
123.05b 136.38
–
–
–
–
s
124.05
28.16
134.46
141.41,
141.49
174.20
160.37
150.16
150.49
136.64
–
97
28.74
97
11
12
13
93
91
93
129
75
85
–
–
–
–
–
–
82.76 t
82.91 t
82.65 t
100
98
96
26.04
27.30 101
28.08
28.21
91
34.50
28.87
29.56
29.46
128.07
–
36.90
39.46
38.14
38.38
0.05
94
92
s
–
–
–
–
82.58 t
96
14
15
81
88
oil
108
–
–
–
–
191.61 d
70.63 d
200.03 d
69.36 d
199.61 d
79.72 dd 151, 121.61
163
171 129.44
c
109
104
120
106
14.43
c
–
–
–
–
c
–
–
s
15.79
c
–
–
16
17
18
19
87
85
90
96
110
oil
–
–
–
–
–
–
s
124.28b 134.39
16.92 d,
−0.58 d,
2JPP 45.4
17.14 d,
39.08 d,
2JPP 43.7
17.15 d,
38.95 d,
2JPP 43.7
33.23
81.25 dd 147,
102
32.08
22.44
93 27.82b
141.37
172.45
16
19
oil
81.25 dd 148,
106
98
28.50
c
c
c
c
132
5.09 d
5.48 d
4.93 d
5.27 d
4.70 d
5.50 d
4.32 t
5.38 d
4.32 t
5.59 d
3.77 t
3.84 t
–
7
10
8
9
8
8
20
8
20
8
19
18
–
67.84 d
70.56 d
70.38 d
72.66 d
71.86 d
72.66 d
51.38 t
69.95 d
51.38 t
70.30 d
50.99 t
50.03 t
73.75 t
78.13 t
97
112
95
110
112
110
84
100
84
100
77
–
–
–
–
–
–
–
–
–
–
–
–
–
30.15
–
–
–
20
21
22
98
97
97
139
117
235
24.92
85
28.04
159.27
149.36
–
14
14
–
–
–
42.85
44.0
31.22
27.42
78 27.76b
c
–
–
–
–
93
74
s
–
–
c
c
c
–
–
–
–
–
31.78
–
23
24
25
26
96
97
98
97
105
29.50
28.37
27.49
28.64
123.98
27.73
158.63
162.68
137.53
142.33,
142.41
174.0
158.37
159.72
–
15
15
s
8
8
37.62
39.10
16.51
45.88
110
78
d
146 127.99
91 128.53
d
–
–
93
d
27
28
29
30
94
97
97
95
–
–
–
–
8
78.18 t
78.72 t
77.02 t
69.05 d
205.86 d
93
91
102
102
115
24.96
26.67
92
96
96
–
35.17
27.19
28.36
–
s
43.76
39.80
43.13
18.78
119
152
165
–
–
14
17
–
27.40
c
5.78 d
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Functionalized Mono- and Bisphosphinates with 2,6-Di-tert-butyl-4-methylphenol Fragments 567
TABLE 1 Continued
Compound Yield (%) Mp (◦C) δH C1H 2JPH
δ (C1)
1JPC δ(C2), d JPC δ(C3), s δ(C4), d JPC
δ , s
P
d
31
32
33
91
92
92
–
–
–
–
–
–
76.54 t
146
127.41
31.66
22.21
s
123.86 137.76
s
18.54 d,
14.95 d,
2JPP 38.9
17.97 d,
43.59 d,
2JPP 32.4
17.93 d,
43.10 d,
2JPP 35.6
oil
oil
77.77 dd 148,
96
94
94
27.84
26.83
142.50
173.18
15
15
77.70 dd 153,
93
aFor 1, Bp in ◦C (P, mmHg). All signals of alkyl, aryl, and trimethylsilyl groups are in the standard area. The following fragments of compounds
1–33 are presented now: PC1HO (d), PC1 O (d), PC1HP (t), PC1HP (t or dd), and PC2C3C4. The 1H NMR spectra of products fragments show
expected signals that look like sometimes as overlapping multiplets. According to the NMR spectra, the compounds 2–7,12,13,15,19,22 are
mixtures of two stereoisomers. Their ratio was determined from the 1H and 31P NMR spectra. The ratio is 55:45 (for 2–4,19), 60:40 (for 5,15),
4
2
N
3
70:30 (for 12,13,22), 75:25 (for 6,7). The spectral parameters of the major isomer are given first. The fragments PC2C3C4 are
for 1;
Bu-t
3
4
2
OH
Bu-t
4
C2H2C3H2
4
4
C2H2C3H2
C2H2C3H2
N
N
N
for 3,6,12,20,23,28;
for 4,7,13,21,24,29;
for 8,9,14,16,25,31;
for 10,17,26,32;
4
C2H2C3H2
2
3
4
O
for 11,27; C H2C H2C O for 18,23.
bd (JPC) for compounds: 1 (4), 4 (3), 17 (3), 21 (3); t (JPC) for compounds: 8 (4.5), 16 (4).
cIn 13C NMR spectra, the signals of pyridine and phenolic fragments of these compounds look as overlapping multiplets.
dThis compound is decomposed by heating.
TABLE 2 Elemental Analyses Data of Compounds 2–33a
Calcd. (%)
Found (%)
H
Compound
Empirical Formula
Formula Weight
C
H
C
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
C30H54NO5PSi
C28H48NO4PSi32
C28H48NO4PSi2
624.00
549.84
549.84
851.27
702.96
702.96
580.73
757.23
789.17
803.16
791.15
791.15
370.42
549.80
668.98
684.94
725.03
408.45
405.47
405.47
562.54
558.60
558.60
396.33
57.75
61.17
61.17
55.03
59.80
59.80
53.78
47.59
60.88
53.84
57.69
57.69
61.61
58.99
50.27
57.87
51.36
61.75
65.17
65.17
57.65
62.36
62.36
45.46
8.72
8.80
8.80
8.05
8.03
8.03
8.68
8.78
8.43
8.53
8.15
8.15
8.43
8.07
8.74
8.54
8.62
7.65
7.95
7.95
6.45
7.22
7.22
6.61
57.72
60.98
60.95
54.89
59.74
59.66
53.59
47.48
60.65
53.66
57.52
57.55
61.48
58.81
49.92
57.73
51.23
61.59
64.97
64.92
57.52
62.12
62.23
45.28
8.64
8.72
8.69
7.94
7.96
7.91
8.57
8.67
8.37
8.44
8.12
8.07
8.35
8.01
8.68
8.49
8.52
7.56
8.02
7.99
6.49
7.26
7.28
6.68
C39H68N O7P Si
C
35H56N2O5P2Si4
C35H56N2O5P2Si2
C26H50O28P2Si
2
2
C30H66O P Si5
C40H66O86P22Si3
C36H68N2O8P2Si3
C38H64N2O6P2Si3
C
C
38H64N2O6P2Si3
19H31O5P
C27H44NO5PSi
C
28H58O8P2Si32
C33H58O7P Si
C
C
C
C
31H62O9P22Si23
21H31NO5P
22H32NO4P
22H32NO4P
C27H36N O7P
C29H40N2O5P2
C
C
29H40N2O5P2
2
15H26O28P2
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

568 Prishchenko et al.
TABLE 2 (Continued)
Calcd. (%)
Found (%)
Compound
Empirical Formula
Formula Weight
C
H
C
H
26
27
28
29
30
31
32
33
C31H42O6P2
C26H42N2O8P2
572.62
572.68
574.60
574.60
405.43
452.43
540.58
508.48
65.02
54.54
60.62
60.62
62.21
50.44
59.99
51.97
7.39
7.39
7.02
7.02
6.96
7.57
7.83
7.57
64.89
54.43
60.49
60.47
61.98
50.07
59.65
51.59
7.47
7.35
7.08
6.98
7.03
7.52
7.74
7.46
C29H40N2O6P2
C29H40N2O6P2
C21H28NO5P
C19H34O8P2
C27H42O7P
C22H38O9P22
aPhosphonite 1 is extremely readily oxidized and hydrolyzed, and therefore it was analyzed in form of the corresponding adduct with aldehyde
A (phosphinate 2).
[2] Tyurin, V. Yu.; Gracheva, Yu. A.; Milaeva, E. R.;
Prishchenko, A. A.; Livantsov, M. V.; Novikova, O.
P.; Livantsova, L. I.; Maryashkin, A. V.; Bubnov, M.
P.; Kozhanov, K. A.; Cherkasov, V. K. Russ Chem Bull
2007, 744–750.
[3] Coppinger, G. M.; Campbell, T. W. J Am Chem Soc
1953, 75, 734–736.
15 mL of hexane was added to the residue, and
the mixture was cooled to 0◦C. The precipitated
white crystals were filtered off and kept in a vacuum
(0.5 mmHg) for 1 h. Bisphosphonate 8 was obtained
with yield of 8 g.
Compounds 9–18 were prepared similarly.
[4] Popov, L. K.; Egidis, F. M.; Ershov, V. V. Izv Akad
Nauk Ser Khim 1968, 902–904 (in Russian).
[5] Ivakhnenko, E. P.; Shif, A. I.; Prokofiev, A. I.;
Olekhnovich, L. P.; Minkin, V. I. Zh Org Khim 1989,
25, 357 (in Russian).
[6] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Petrosyan, V. S. Heteroatom Chem
2008, 19, 345–351.
[7] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Petrosyan, V. S. Heteroatom Chem
2008, 19, 352–359.
[8] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Petrosyan, V. S. Heteroatom Chem
2008, 19, 418–428.
Pyrid-3-yl(hydroxy)methyl 3,5-di-tert-butyl-4-
hydroxyphenyl(hydroxy)methylphosphinic Acid
(19)
Phosphonate 2, 10.7 g, was added with stirring to
60 mL of methanol and was cooled to 10◦C. The mix-
ture was heated to boiling, the solvent was distilled
off, and residue was kept in a vacuum (1 mmHg) for
1 h to obtain 6.7 g of acid 19.
Acids 20–23 were prepared similarly.
[9] Ebetino, F. H. Phosphorus Sulfur Silicon Relat Elem
1999, 144–146, 9.
[10] Matkovskaya, T. A., Popov, K. I.; Yurieva, E. A. Bis-
phosphonates. Properties, Structure, and Medical
Applications; Khimiya: Moscow, 2001 (in Russian).
[11] Kolodiazhnyi, O. I. Usp Khim 2006, 75, 254–282 (in
Russian).
REFERENCES
[1] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Milaeva, E. R. Heteroatom Chem
(in press).
[12] Sekine, M.; Hata, T. Chem Commun 1978, 285.
Heteroatom Chemistry DOI 10.1002/hc