Imines derived from 4-methyl-4-diphenylphosphorylpentan-2-one and potassium salts of aminocarboxylic acids

Article abstract of DOI:10.1134/S1070363217040363

An effective procedure for the preparation of imines based on 4-methyl-4-diphenylphosphorylpentan-2-one, aminoacetic, aminopropionic, and aminobutyric acids with yields of 90–95% was developed. Reaction of dimephosphone (4-methyl-4-dimethoxyphosphorilpent

Full text of DOI:10.1134/S1070363217040363

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 4, pp. 882–884. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © M.N. Dimukhametov, V.F. Mironov, D.A. Tatarinov, 2017, published in Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 4, pp. 686–
6
88.
LETTERS
TO THE EDITOR
Imines Derived
from 4-Methyl-4-diphenylphosphorylpentan-2-one
and Potassium Salts of Aminocarboxylic Acids
a
a,b
a,b
M. N. Dimukhametov , V. F. Mironov *, and D. A. Tatarinov
a
Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences,
ul. Akademika Arbuzova 8, Kazan, Tatarstan, 420088 Russia
*
e-mail: mironov@iopc.ru
b
Kazan (Volga Region) Federal University, Kazan, Tatarstan, Russia
Received January 19, 2017
Abstract—An effective procedure for the preparation of imines based on 4-methyl-4-diphenylphosphoryl-
pentan-2-one, aminoacetic, aminopropionic, and aminobutyric acids with yields of 90–95% was developed.
Reaction of dimephosphone (4-methyl-4-dimethoxyphosphorilpentan-2-one) with potassium salts of these
amino acids led to methylation of the carboxy group of the amino acid to form potassium salt of 2-methyl-4-
oxopentylphosphonic acid methyl ester.
Keywords: γ-phosphoryl ketone, 4-phosphorylimine, dimephosphone, aminocarboxylic acid, dimephosphone
potassium salt
DOI: 10.1134/S1070363217040363
Among the aza-analogs of γ-phosphoryl ketones the
acids are of considerable interest as a platform for the
preparation of new biologically active compounds, P-
analogs of dipeptides.
isoniazid derived hydrazones possessing high antituber-
culosis activity and low toxicity are noticeably
distinguished [1–4]. Oximes and imines of γ-phos-
phoryl ketones are also known [5–8], as well as oximes
and some imines derived from γ-phosphoryl aldehydes
9]. We have not found in the literature any data on
imines based on γ-phosphoryl ketones and amino-
carboxylic acids. Conjugates with aminocarboxylic
Here we report on an effective approach to the
preparation of such derivatives based on the potassium
salts of glycine, β-aminopropionic and γ-aminobutanoic
acids 1a–1c with the use of 4-methyl-4-diphenyl-
phosphorylpentan-2-one 2a as a phosphorus com-
[
Scheme 1.
O
R
6'
3'
1
'
5'
7
Ph
'-10'
2
2'
_
P
Δ
_
1
K+ OOC
+
N
4'
P
n
NH2
+
R
K OOC
n
MeOH
R = Ph
Ph
O
O
2
a, 2b
1
a−1c
3a−3c
MeOH
Δ
R = OMe
1
6
5
_
+
2
O K
3
4
n
O
P
+ MeOOC
NH2
OMe
O
4
b
5a−5c
n = 1 (a), 2 (b), 3 (c); R = Ph (2a), OMe (2b).
8
82

IMINES DERIVED FROM 4-METHYL-4-DIPHENYLPHOSPHORYLPENTAN-2-ONE
883
1
0'
1
3
4
ponent. The reactions were carried out in methanol
with heating for 4 h. The resulting products 3 were
isolated as pale yellow oily substances with yields of
(C , J = 162.0, J = 7.4, J = 1.7), 131.11 d.t
HC
HC
3
PC
7
'
1
7'
(d) (C , E, J = 91.8, J = 7.3), 130.83 d.t (d) (C ,
PC
HC
1
3
9'
Z, J = 92.0, J = 7.3), 129.98 d.d.d (d) (С , Z,
PC
HC
1
3
3
9
0–95%. Their structure was proved by NMR and
J
= 162.2, J = 11.1, J = 7.2), 129.90 d.d.d (d)
HC
9'
PC HC
1
1
3
3
mass spectrometry. In the H NMR spectra of com-
pounds 3 the protons at the C atom of the E-isomer
(С , E, J = 162.2, J = 11.1, J = 7.2), 50.16 t.t
HC
PC
HC
3
'
3
1
2
3' 1
(s) (С , J = 135.9, J = 4.8), 42.0 t.m (s) (C , J
125.3, J = 2.7, J = 2.7), 39.55 br.d (br.m) (С ,
JPC = 69.4), 40.03 t.t (s) (С , E, J = 135.8, J
4.4), 39.02 t.t (s) (С , Z, J = 126.5, J = 4.0),
22.44 br.q.m (br.s) (С , J = 128.0, J = 5.0, J
2.5), 21.91 br.q (br.s) (С , J = 127.5, J = 3.6).
P–{ H} NMR spectrum, δ , ppm: 40.5, 39.7 (2 : 1).
Mass spectrum (ESI), m/z: 370 [M – K] (calculated
=
HC
HC
HC
3
3
4'
appeared as the AX part of the AMX system in the
HC HC
2
3
1
2
1
2
ranges of 3.2–3.4 and 2.2–2.3 ppm ( J = 7.4, J
7
=
=
HH
PH
HC
HC
1
3
2
1
2
.4 Hz). In the C NMR spectra, the carbon of the
HC HC
5
',6'
1
3
3
imino group appeared at 170.5–172.5 ppm as a doublet
=
HC
1'
HC
HC
3
1
3
(
JPC = 14.7–15.2 Hz). In the IR spectra a strong
HC
HC
–
1
31
1
absorption band was present at 1570 cm due to the
stretching vibrations of C=N bond.
P
–
for C H NO P: 370).
2
0
23
3
To our surprise, reaction of dimephosphone (4-
methyl-4-dimethoxyphosphorylpentan-2-one) 2b with
potassium salts of these amino acids led to methylation
of the carboxy group of the amino acid to form
potassium salt of methyl 2-methyl-4-oxo-pentylphos-
phonate 4b, the structure of which was confirmed by
NMR method. The alkylation of the carboxylate anion
with the formation of methyl esters of aminocarboxylic
Potassium 2-[4-methyl-4-(diphenylphosphoryl)pent-
1
3
2
-ylideneamino]butyrate (3c). Yield 95%. С NMR
1
3
spectrum, δ , ppm (J, Hz): 182.11 t.t (s) (C , Z, J
=
=
C
HC
2
1
3
2
6
4
.2, J = 4.2), 182.02 t.t (s) (C , E, J = 6.2, J
HC HC
HC
2
' 3
.2), 170.47 br.m (br.d) (С , J = 14.7), 133.51 d.m
PC
8
'
1
2
3
3
(
d) (C , E, J = 161.7, J = 8.1, J = 7.1, J
=
HC
PC
HC
HC
8
'
1
2
7
.1), 133.46 d.m (d) (C , Z, J = 161.7, J = 8.1,
HC
PC
10' 1
3
3
1
JHC = 7.1, JHC = 7.1), 133.49 d.m (d) (C , JHC =
acids was also established by H NMR data and by
comparison of the obtained spectral characteristics
with the literature data [10].
3
4
7'
1
62.0, J = 7.1, J = 2.3), 131.08 d.t (d) (C , E,
HC PC
1
3
7'
1
JPC = 91.7, J = 7.4), 130.77 d.t (d) (C , Z, J
=
HC
PC
3
9'
1
9
2.4, J = 7.4), 129.93 d.d.d (d) (С , Z, J = 162.0,
HC
HC
9'
3
3
1
JPC = 11.0, J = 6.5), 129.87 d.d.d (d) (С , E, J
=
=
=
HC
HC
Potassium 2-[4-methyl-4-(diphenylphosphoryl)pent-
3
3
4 1
1
3
162.0, JPC = 11.0, JHC = 6.5), 52.60 t.m (s) (С , JHC
1
2
-ylideneamino]acetate (3a). Yield 90%. C NMR
2
3
3' 1
33.4, J = 4.2, J = 4.2), 42.30 t.m (s) (C , J
HC HC HC
spectrum, δ , ppm (J, Hz) (the data given in paren-
C
3
3
4'
1
3
1
1
136.1, JHC = 5.0, JHC = 5.1), 38.50 br.d (br.m) (С ,
theses are for the C–{ H} spectra): 180.42 t (s) (C ,
JHC = 4.4), 172.50 br.m (br.d) (С , J = 15.8),
33.48 d.m (d) (C , J = 162.1, J = 8.4, J
1
2
1
2
2
2'
3
J
PC = 69.6), 37.12 t.m (s) (С , Z, JHC = 124.7, JHC
=
=
=
=
=
PC
3
2
1
2
8
'
1
2
3
3.7, JHC = 3.7), 36.75 t.m (s) (С , Z, JHC = 125.4, JHC
3.6, JHC = 3.6), 29.57 t.m (s) (C , E, JHC = 127.2, JHC
3.7, JHC = 3.7), 28.46 t.m (s) (C , Z, JHC = 128.2, JHC
3.7, JHC = 3.7), 22.44 br.q.m (br.s) (С , E, Z, JHC
1
=
HC
PC
10'
HC
3
3
1
2
3
1
7
.3, J = 7.3), 133.57 d.m (d) (C , J = 162.0,
HC
HC
1
2
3
1
2
3
4
7'
JHC = 7.3, J = 1.8), 130.64 d.t (d) (C , J = 91.7,
PC
PC
2
5',6'
1
3
9'
1
3
JHC = 7.3), 129.95 d.d.d (d) (С , J = 162.8, J
=
HC
PC
3
3
1'
3
2
1
128.0, JHC = 4.4, JHC = 4.4), 21.85 br.q (br.s) (С ,
1
1.0, J = 7.3), 57.08 t (s) (С , J = 133.3), 46.20
HC HC
1
3
31
1
3
'
1
4'
1
J
HC = 128.7, JHC = 3.6). P–{ H} NMR spectrum, δ
,
P
t.m (s) (C , J = 135.0), 37.15 br.d (br.m) (С , J
=
=
HC
PC
5
',6'
1
3
ppm: 40.2, 39.5 (5:2). Mass spectrum (ESI), m/z: 384
6
9.7), 21.72 br.q.m (br.s) (С , J = 128.4, J
HC HC
–
3
1'
1
[M – K] (calculated for C22H27NO P: 384).
3
5
.1, J = 4.4), 22.42 br.q (br.s) (С , J = 128.4,
HC HC
3
31
1
JHC = 4.2–4.4). P–{ H} NMR spectrum, δ , ppm:
Potassium salt of 2-methyl-4-oxopentylphosphonic
P
4
0.8, 40.0 (1 : 6). Mass spectrum (ESI), m/z: 356 [M –
acid methyl ester (4b). Yield 95%, pale yellow thick
oily substance. Н NMR spectrum, δ, ppm (J, Hz):
–
1
K] (calculated for C H NO P: 356).
2
0
23
3
3
3 3
3
.61 d (3H, OCH , J = 9.5), 2.65 d (2H, H , J
=
3
PH
PH
1
5,6 3
Potassium 2-[4-methyl-4-(diphenylphosphoryl)pent-
10.0), 2.19 s (3H, H ), 1.24 d (6H, H , J = 15.3).
С NMR spectrum, δ , ppm (J, Hz): 23.37 br.q.m (d)
PH
13
13
2
-ylideneamino]propionate (3b). Yield 93%. С NMR
C
1
3
1
1
2
2 1
spectrum, δ , ppm (J, Hz): 180.58 t.t (s) (C , Z, J
6
4
=
=
(С , J = 127.5, J = 3.5), 36.02 d.m (d) (С , J
C
HC
НC PC РC
2
1
3
2
2
2
3 1
.2, J = 3.2), 181.05 t.t (s) (C , E, J = 5.8, J
.7), 170.58 br.m (br.d) (С , J = 15.2), 133.56 d.m
140.4, J = 4.0, J = 4.0), 50.67 br.t (br.s) (С , J
НC
=
HC
HC
HC
HC
HC
2
'
3
4
3
2
PC
127.0), 212.18 d.q.t (d) (С , J = 13.4, J = 5.7,
JНC = 5.7), 33.06 br.t (br.d) (С , J = 127.5, J
2.1), 23.39 br.q.m (d) (С , J = 127.5, J = 3.5),
67.53 br.t.m (br.s) (NC , J = 143.8), 52.21 q.d (d)
НC
PC НC
8
'
1
2
3
3
2
5
1
4
(
d) (C , E, J = 160.7, J = 8.3, J = 7.7, J
=
=
HC
PC
HC
HC
НC
PC
8
'
1
2
6
1
2
7
.7), 133.51 d.m (d) (C , Z, J = 160.8, J = 8.5,
HC
PC
НC PC
3
3
7 1
JHC = 7.7, J = 7.7), 133.59 and 133.44 two d.m (br.d)
HC
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

8
84
DIMUKHAMETOV et al.
1
2
31
1
(
POCH , J = 144.6, J = 6.6). P–{ H} NMR
4. Mironov, V.F., Buzykin, B.I., Garaev, R.S., Tatari-
nov, D.A., Kashapov, L.R., Chestnova, R.V., Nabiul-
lin, V.N., Ilґyasov, A.V., and Zobova, V.V., Russ.
Chem. Bull., 2014, vol. 63, no. 9, p. 2114. doi 10.1007/
s11172-014-0708-2
3
НC
PC
spectrum: δ 30.5 ppm. Mass spectrum (ESI), m/z: 193
M – K] (calculated for C H O P: 193).
P
–
[
7 14 4
NMR spectra (CD OD) were recorded on a Bruker
3
Avance-600 instrument. IR spectra (film, KBr) were
registered on a Bruker Tensor-27 spectrometer. Mass
spectra were taken on a Bruker AmazonX instrument.
5
. Shagidullin, R.R., Vandyukova, I.I., Zvereva, E.E.,
Vizel, A.O., Shchukina, L.I., and Garaev, R.S., Russ.
Chem. Bull., 2007, vol. 56, no. 7, p. 1298. doi 10.1007/
s11172-007-0198-6
ACKNOWLEDGMENTS
6. Tatarinov, D.A., Mironov, V.F., Kostin, A.A., Miro-
nova, E.V., Krivolapov, D.B., Morozov, V.I., Nabiul-
lin, V.N., Il’yasov, A.V., and Buzykin, B.I., Russ. J.
Gen. Chem., 2014, vol. 84, no. 5, p. 901. doi 10.1134/
S107036321405020X
This work was financially supported by the Russian
Foundation for Basic Research and the Academy of
Sciences of the Republic of Tatarstan (grant no. 16-43-
7
. Issleib, K., Doepfer, K.-P., and Balszuweit, A.,
Phosphorus, Sulfur, Silicon, Relat. Elem., 1983, vol. 14,
no. 2, p. 171. doi 10.1080/03086648308075939
0
2456).
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017