Synthesis and properties of N-phosphorylated aminoaldehydes [4]

Full text of DOI:10.1134/S1070363207020223

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 2, pp. 313 316.
Pleiades Publishing, Ltd., 2007.
Original Russian Text M.B. Gazizov, R.A. Khairullin, A.I. Alekhina, L.R. Bagauva, O.G. Sinyashin, 2007, published in Zhurnal Obshchei Khimii, 2007,
Vol. 77, No. 2, pp. 341 344.
LETTERS
TO THE EDITOR
Synthesis and Properties of N-Phosphorylated Aminoaldehydes
M. B. Gazizova, R. A. Khairullina, A. I. Alekhinaa, L. R. Bagauvaa, and O. G. Sinyashinb
a Kazan State Technological University,
ul. K.Marksa 68, Kazan, Tatarstan, 420015 Russia
e-mail: mukattisg@mail.ru
b Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received September 22, 2006
DOI: 10.1134/S1070363207020223
N-Phosphorylated aminoaldehydes have never been
O2N
reported previously. We found that they can be syn-
thesized by the Todd Atterton reaction of hyd-
NO2
(RO)2P(O)N(Et)CH2CMe2CH=O + H2NNH
rophosphoryl compounds I with 3-alkylamino-substi-
tuted aldehydes II. A mixture of aminoaldehyde and
triethylamine was added dropwise with stirring at 5 C
to a solution of compound I in CCl4. After 1-h stirring
the reaction mixture was heated to 25 C and stirred
additionally for 12 h. Triethylamine hydrochloride
was filtered off, and products III were distilled in
high vacuum.
IIIa IIIe
IV
O2N
c
NO2
(RO)2P(O)N(Et)CH2CMe2CH=NNH
a
b
V
+ H2O,
R1(R2O)PHO + EtNHCH2CMe2CHO
V, R = Me (a), Et (b), i-Pr (c), Bu (d).
I
II
The reaction of aldehydes III with tert-butylamine
was carried out in toluene. The liberated water was
removed by azeotropic distillation. Imines VII were
prepared in high yields.
CCl4 + B
R1(R2O)P(O)N(Et)CH2CMe2CHO,
III
III, R1 = MeO, R2 = Me (a), R1 = EtO, R2 = Et (b),
R1 = i-PrO, R2 = i-Pr (c), R1 = BuO, R2 = Bu (d), R1 = Ph,
R2 = Me (e), B = Et3N.
(RO)2P(O)N(Et)CH2CMe2CH=O + H2NBu-t
III
VI
toluene
reflux
(RO)2P(O)N(Et)CH2CMe2CH=NBu-t + H2O,
VII
The structure of N-phosphorylated aminoaldehydes
III was confirmed by the elemental analysis and H
1
VII, R = Et (b), i-Pr (c), Bu (d).
and 31P NMR spectra. To obtain chemical evidence
for their structure and synthesize polyfunctional phos-
phoruscontaining compounds, aldehydes III were re-
acted with 2,4-dinitrophenylhydrazine (IV), tert-butyl-
amine (VI), lithium aluminum hydride (VII), and
hydrogen dimethyl phosphite (Ia). The reaction with
2,4-dinitrophenylhydrazine was carried out in ethyl
acetate at 70 80 C. Crystallization from hexane gave
hydrazones V in almost quantitative yields.
The reduction with lithium aluminum hydride
(VIII) was carried out in ether under reflux. Inter-
mediate alkoholate IX was carefully decomposed with
water. N-Phosphorylated aminoalcohols X were iso-
lated pure by high-vacuum distillation.
The reaction of aldehyde IIId with dimethyl phos-
phite Ia was carried out under Abramov reaction
313

314
GAZIZOV et al.
ppm: 10.2. Found, %: N 5.40; P 12.00. C9H19NO3P.
4(RO)2P(O)N(Et)CH2CMe2CHO + LiAlH4
IIIa, IIIb VIII
Calculated, %: N 5.48; P 12.16.
3-[(Diisopropoxyphosphoryl)ethylamino]-2,2-
dimethylpropanal (IIIc) was obtained from 19.92 g
of hydrogen diisopropyl phosphite (Ic), 80 ml of CCl4,
15.66 g of aldehyde II, and 12.12 g of triethylamine.
Yield 25.25 g (71%), bp 84 85 C (0.09 mm Hg), nD20
[(RO)2P(O)N(Et)CH2CMe2CH2O]14 [AlLi]4+
ether
IX
4H2O
4(RO)2P(O)N(Et)CH2CMe2CH2OH,
[Al(OH)3 + LiOH]
1
1.4410. H NMR spectrum (CDCl33), , ppm: 0.87 s
X, R = Me (a), Et (b).
(6H, CMe2), 0.87 t (3H, NCH2Me, JHH 7 Hz), 1.1 d
3
(12H, OCHMe2, JHH 7.5 Hz), 2.65 q and 2.80 q (2H,
3
conditions. A mixture of compounds Ia and IIId was
treated with a small piece of sodium. Slight heat re-
lease was initially observed, after which the reaction
mixture was kept at room temperature for 24 h and
neutralized with acetic acid. Volatile admixtures were
removed in high vacuum, and 3-[(dibutoxyphospho-
ryl)ethylamino]-1-(dimethoxyphosphoryl)-2,2-dime-
thylpropan-1-ol (XI) was identified crude.
NCH2Me, JHH 7 Hz), 3.0 s and 3.11 s (2H, NCH2),
3
4.33 q (2H, POCHMe2, JHH 7.5 Hz), 9.47 s (1H,
CHO). 31P NMR spectrum, P, ppm: 9.2. Found, %:
N 5.30, P 11.69. C10H21NO3P. Calculated, %: N 5.28;
P 11.70.
3-[(Dibutoxyphosphoryl)ethylamino]-2,2-dime-
thylpropanal (IIId) was obtained from 23.28 g of
dibutyl hydrogen phosphite (Id), 100 ml of CCl4,
15.2 ml of aldehyde II, and 12.12 g of triethylamine.
Yield 25.71 g (68%), bp 120 C (0.09 mm Hg), nD20
(MeO)2PHO + (BuO)2P(O)N(Et)CH2CMe2CHO
I
IIId
1
1.4456 H NMR spectrum (CDCl3), , ppm: 0.88 t
(BuO)2P(O)N(Et)CH2CMe2CH(O H)P(O)(OMe)2.
3
(6H, CH2Me, JHH 7 Hz), 0.99 s (6H, CMe2); 0.98 t
XI
3
(3H, NCH2Me, JHH 7 Hz), 1.12 1.75 m (8H,
3
CH2CH2, JHH 7.5 Hz), 2.78 q and 2.93 q (2H,
Reaction of hydrogen dimethyl phosphite (Ia)
with 3-(ethylamino)-2,2-dimethylpropanal (II). A
mixture of 13.1 g of aldehyde II and 10.1 g
of triethylamine was added dropwise with stirring
under dry nitrogen to a solution of 11.17 g of Ia in
80 ml of CCl4. After 1-h stirring, the reaction mixture
was heated to 25 C and stirred additionally for 12 h.
The crystals formed were filtered off and twice
washed with CCl4. The solvent was removed, and the
residue was distilled in high vacuum to give 14.74 g
3
NCH2Me, JHH 7 Hz), 3.1 and 3.22 s (2H, NCH2),
3
3
3.85 q (4H, POCH2, JHH = JPH 7.5 Hz), 9.57 s (1H,
CHO). 31P NMR spectrum, P, ppm: 10.6. Found, %:
N 5.05; P 11.16. C11H23NO3P. Calculated, %: N 5.02;
P 11.11.
3-[(Methoxy)phenylphosphoryl)ethylamino]-2,2-
dimethylpropanal (IIIe) was obtained from 14.04 g
of hydrogen methyl phenylphosphonate (Ie), 80 ml of
CCl4, 11.67 g of aldehyde II, and 9.09 g of triethyl-
amine. Yield 15.61 g (61%), bp 130 131 C (0.08 mm
(62%) of compound IIIa, bp 82 C (0.09 mm Hg), nD20
1.4480. 1H NMR spectrum (acetone-d6)1, , ppm:
Hg), n2D0 1.5149. H NMR spectrum (CDCl3), , ppm:
1
3
0.75 s (6H, CMe2), 0.83 t (3H, NCH2Me, JHH 7 Hz),
0.95 s (5H, CNe2), 0.94 t (3H, NCH2Me, JHH 7 Hz),
3
3
2.53 q and 2.65 q (2H, NCH2Me, JHH 7 Hz), 3.0 and
2.73 q amd 2.85 q (2H, NCH2Me, JHH 7 Hz), 3.05 s
3
3
3.11 s (2H, NCH2), 3.53 d (3H, POMe, JPH 10 Hz),
and 3.16 s (2H, NCH2), 3.51 d (6H, POMe, JPH
10.5 Hz), 9.5 s (1H, CHO). 31P NMR spectrum,
,
7.1 7.3 m (5H, C6H5), 9.35 s (1H, CHO). 31P NMR
spectrum, P, ppm: 23.4 23.6. Found, %: N 5.00,
P 10.90. C14H22NO3P. Calculated, %: N 4.95; P 10.95.
P
ppm: 12.9. Found, %: N 5.88; P 13.10. C8H17NO3P.
Calculated, %: N 5.96; P 13.18.
3-[(Diethoxyphosphoryl)ethylamino]-2,2-di-
methylpropanal (IIIb) was obtained from 16.56 g of
diethyl hydrogen phosphite (Ib), 80 ml of CCl4, 15 g
of aldehyde II, and 12.12 g of triethylamine IIIb.
Yield 20.02 g (65%), bp 92 95 C (0.09 mm Hg), nD20
1.4440. 1H NMR spectrum (acetone-d6), , ppm:
3-[(Dimethoxyphosphoryl)ethylamino]-2,2-di-
methylpropanal 2,4-dinitrophenylhydrazone (IVa).
To a solution of 3.36 g of 2,4-dinitrophenylhydrazine
in 75 ml of ethyl acetate, 4.02 g of aldehyde IIa was
added dropwise at 70 78 C. The resulting mixture
was cooled to room temperature and left for 7 h. The
crystals that formed after removal of half the solvent
were filtered off, washed with hexane, and dried to
obtain compound IVa, yield 4.6 g (65%), mp 165
3
0.93 s (6H, CMe2), 0.93 t (3H, NCH2Me, JHH 7 Hz);
3
1.18 t (6H, OCH2Me, JHH 7.5 Hz), 2.75 q and 2.90 q
3
(2H, NCH2Me, JHH 7 Hz), 3.07 s and 3.18 s (2H,
3
3
1
NCH2), 3.85 quintet (4H, POCH2Me, JHH = JPH
166 g (from hexane). H NMR spectrum, , ppm:
7.5 Hz), 9.54 s (1H, CHO). 31P NMR spectrum, ,
1.10 t (3H, NCH2Me, JHH 7.5 Hz); 1.16 s (6H,
3
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SYNTHESIS AND PROPERTIES OF N-PHOSPHORYLATED AMINOALDEHYDES
315
2
CMe2), 2.95 q and 3.13 q (2H, NCH2Me, JHH
2.9 s and 3.01 s (2H, NCH2), 3.86 quintet (4H,
3
3
7.5 Hz), 3.15 s and 3.3 s (2H, NCH2), 3.5 d (6H,
POCH2Me, JHH = JPH 7.5 Hz), 7.5 s (1H, CH=N).
Found, %: N 8.9; P 10.2. C15H33N2O3P. Calculated,
%: N 9.1; P 10.0.
POMe, JPH 12 Hz); 7.63 s (1H, CH=N), 8.0 d (1Ha,
3
JH H 10 Hz), 8.40 d.d (1Hb, JH H 10 Hz, JH H
3
3
4
a
b
a
b
c b
2.5 Hz), 9.24 d (1Hc, JH H 2.5 Hz), 11.1 s (1H, NH).
31P NMR spectrum, P, ppm: 10.5. Found, %: N
16.50, P 7.65. C15H24N5O5P. Calculated, %: N 16.65,
P 7.80.
4
c
b
N-tert-Butyl-N-[3-[(diisopropoxyphosphoryl)-
ethylamino]-2,2-dimethylpropylidene]amine (VIIc)
was obtained from 2 g of tert-butylamine, 30 ml of
anhydrous toluene, and 8.24 g of aldehyde IIIc. Yield
6.83 g (70%), bp 89 C (0.05 mm Hg), n2D0 1.4403.
Found, %: N 7.8, P 8.9. C17H37N2O3P. Calculated, %:
N 8.3, P 9.2.
3-[(Diethoxyphosphoryl)ethylamino]-2,2-di-
methylpropanal 2,4-dinitrophenylhydrazone (IVb)
was obtained from 3.74 g of 2,4-dinitrophenylhydra-
zine, 75 ml of ethyl acetate, and 5 g of aldehyde IIIb.
Yield 5.21 g (62%), mp 139 131 C (from hexane).
31P NMR spectrum, P, ppm: 10.5. Found, %: N 16.9,
P 6.8. C17H28N5O5P. Calculated, %: N 16.2; P 7.1.
N-tert-Butyl-N-[3-[(Dibutoxyphosphoryl)ethyl-
amino]-2,2-dimethylpropylidene]amine (VIId) was
obtained from 3 g of tert-butylamine, 50 ml of ab-
solute toluene, and 9.92 g of aldehyde IIId. Yield
11.44 g (72%), bp 97 98 C (0.05 mm Hg), n2D0 1.4480.
1H NMR spectrum (acetone-d6), , ppm: 0.85 s (6H,
3-[(Diisopropoxyphosphoryl)ethylamino]-2,2-
dimethylpropanal 2,4-dinitrophenylhydrazone
(IVc) was obtained from 3.04 g of 2,4-dinitriphenyl-
hydrazine, 80 ml of ethyl acetate, and 4.5 g of alde-
hyde IIIc. Yield 4.87 g (67%), mp 94 95 C. 1H NMR
spectrum (acetone-d6), , ppm: 0.98 t (3H, NCH2Me,
3JHH 7 Hz), 1.04 s (6H, CMe2), 1.08 d.d (12H,
3
CMe2), 0.85 t [6H, O(CH2)3Me, JHH 7 Hz), 0.85 t
3
(3H, NCH2Me, JHH 7 Hz), 1.0 s (9H, CMe3), 1.1
1.35 m (8H, POCH2CH2CH2Me), 2.78 q and 2.90 q
3
(2H, NCH2Me, JHH 7 Hz), 2.96 s and 3.07 s (2H,
NCH2), 3.79 q (4H, POCH2, 3JHH = 3JPH 7 Hz), 7.48 s
(1H, CH=N). Found, %: N 7.4, P 8.4. C19H41N2O3P.
Calculated, %: N 7.7, P 8.5.
3
Me2CHO, JHH 7 Hz), 2.90 q and 3.08 q (2H,
NCH2Me, JHH 7 Hz), 2.98 s and 3.1 s (2H, NCH2),
3
3
4.3 q (2H, Me23CH, JHH 7.5 Hz); 7.68 s (1H, CH=N),
Reduction of 3-[(dimethoxyphosphoryl)ethyl-
amino]-2,2-dimethylpropanal (III). To a suspension
of 0.19 g of lithium aluminum hydride (10% excess)
in 50 ml of absolute ether, a solution of 4.81 g of
aldehyde IIIa in 20 ml of ether was added dropwise
at a rate providing moderate boiling of the reaction
mixture. After 2 h, the solution was cooled with ice
water, and the intermediate alcoholate IX was decom-
posed with 100 ml of cold water. Metal hydroxides
were filtered off, the aqueous layer was removed, and
the ethereal layer was dried over MgSO4. The ether
was removed, and the residue was distilled in a vacuum
to give 1.55 g (40%) of 3-[(dimethoxyphosphoryl)-
ethylamino]-2,2-dimethylpropan-1-ol (XIa), bp 103 C
7.88 d (1Ha, JH H 10 Hz), 8.23 d.d (1Hb, JH H
3
a
b
a b
10 Hz), 8.23 d.d (1Hb, JH H 10 Hz, JH H 2.5 Hz),
3
4
a
b
c b
8.98 d (1Hc, JH H 2.5 Hz), 11.1 s (1H, NH). 31P
NMR spectrum, P, ppm: 10.9. Found, %: N 14.8, P
6.3. C15H32N5O5P. Calculated, %: N 15.2; P 6.7.
4
c
b
3-[(Dibutoxyphosphoryl)ethylamino]-2,2-di-
methylpropanal 2,4-dinitrophenylhydrazone (IVd)
was obtained from 2.89 g of 2,4-dinitrophenylhydra-
zine, 80 ml of ethyl acetate, and 4.7 g of aldehyde
IIId. Yield 4.31 g (59%), mp 97 98 C (from hexane).
31P NMR spectrum, P, ppm: 11.8. Found, %: N 14.8,
P 6.3. C19H32N5O5P. Calculated, %: N 15.2, P 6.7.
(0.09 mm Hg), n2D0 1.4535. 1H NMR spectrum
Reaction of 3-[(diethoxyphosphoryl)ethylami-
no]-2,2-dimethylpropanal (IIIb) with tert-butyl-
amine. To a solution of 0.74 g of tert-butylamine in
20 ml of anhydrous toluene, a solution of 3.4 g of
compound IIIb in 10 ml of toluene was added drop-
wise with stirring. The reaction mixture was refluxed
for 6 h with azeotropic distillation of water. The sol-
vent was then removed, and the residue was distilled
in high vacuum to give 2.56 g (63%) of N-tert-butyl-
N-[3-[(diethoxyphosphoryl)ethylamino]-2,2-dimethyl-
propylidene]amine (VIIb), bp 92 93 C (0.08 mm Hg),
(CDCl3), , ppm: 0.38 s (6H, CMe2), 0.68 t (3H,
3
NCH2Me, JHH 7 Hz), 2.55 q and 2.71 q (2H,
3
NCH2Me, JHH 7 Hz), 2.37 and 2.49 s (2H, NCH2),
3
2.74 d (2H, CH2OH, JHH 7 Hz), 3.25 d (6H, POMe,
3
3JHH 10 Hz), 4.10 t (1H, OH, JHH 7.5 Hz). 31P NMR
spectrum, P, ppm: 10.00. Found, %: N 5.80, P 12.95.
C9H22NO4P. Calculated, %: N 5.86, P 12.93.
3-[(Diethoxyphosphoryl)ethylamino]-2,2-di-
methylpropan-1-ol (Xb) was obtained from 0.11 g
of lithium aluminum hydride in 40 ml of ether and
3.12 g of aldehyde IIIb in 30 ml of ether. Yield
1.21 g (41%), bp 110 C (0.09 mm Hg), n2D0 1.4432.
1H NMR spectrum (CDCl3), , ppm: 0.7 s (6H,
n2D0 1.4450. H NMR spectrum (acetone-d6), , ppm:
1
3
0.93 s (6H, CMe2), 0.93 t (3H, NCH2Me, JHH 7 Hz),
3
1.03 s (9H, CMe3), 1.18 t (6H, 2OCH2Me, JHH
7.5 Hz), 2.78 q and 2.90 q (2H, NCH2Me, 3JHH 7 Hz),
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316
GAZIZOV et al.
3
CMe2), 0.89 t (3H, NCH2Me, JHH 7 Hz), 1.13 t (6H,
under argon. The reaction mixture warmed up by 5 C.
It was stirred for 24 h at 20 C, neutralized with acetic
acid, and volatile products were removed in high
vacuum to give 3.18 g (90%) of crude 3-[(dibutoxy-
phosphoryl)ethylamino]-1-(dimethoxyphosphoryl)-
3
POCH2Me, JHH 7.5 Hz), 2.6 q and 2.73 q (2H,
NCH2Me, JHH 7 Hz), 2.99 d (2H, CH2OH, JHH
7.5 Hz), 2.80 and 2.93 q (2H, NCH2Me, JHH 7 Hz),
3.85 quintet (4H, POCH23Me, JHH 7.5 Hz, JPH
7.5 Hz), 4.32 t (1H, OH, JHH 7.5 Hz). Found, %:
N 5.30, P 11.66. C11H26NO4P. Calculated, %: N 5.24,
P 11.61.
3
3
3
3
3
2,2-dimethylpropan-1-ol (XI). 31P NMR spectrum,
,
P
ppm: 12 and 26. Found, %: N 3.15, P 7.22. C17H39
NO7P2. Calculated, %: N 3.25, P 7.19.
1
Reaction of 3-[(dibutoxyphosphoryl)ethyl-
amino]-2,2-dimethylpropanal (IIId) with hydrogen
dimethyl phosphite. To a mixture of aldehyde III,
3 g, and 7 g of Ia, a small piece of sodium was added
The H NMR spectra were measured on a Tesla
BS-567A spectrometer (100 MHz) against TMS. The
31P NMR spectra were measured on a CPX-100 spec-
trometer (36.5 MHz) against 85% H3PO4.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 2 2007