Kinetics and mechanism of the Pudovik reaction in the azomethine series: I. Addition of dimethyl hydrogen phosphite to N-isopropylbenzalimines

Article abstract of DOI:10.1023/A:1020794530963

For a series of phenyl-substituted N-isopropylbenzalimines, the effect of substituent on their capability to add dimethyl hydrogen phosphite was studied qualitatively in the condensed phase (DTA) and quantitatively (with determination of the kinetic and activation parameters) in 2-propanol solutions with spectrophotometric monitoring of the reaction. A reaction mechanism was proposed, involving formation of a highly organized four-membered transition state.

Full text of DOI:10.1023/A:1020794530963

Russian Journal of General Chemistry, Vol. 72, No. 7, 2002, pp. 1067 1070. Translated from Zhurnal Obshchei Khimii, Vol. 72, No. 7, 2002,
pp. 1141 1144.
Original Russian Text Copyright
2002 by Sobanov, Zolotukhin, Galkin, Cherkasov, Pudovik.
Kinetics and Mechanism of the Pudovik Reaction
in the Azomethine Series:
I. Addition of Dimethyl Hydrogen Phosphite
to N-Isopropylbenzalimines
A. A. Sobanov, A. V. Zolotukhin, V. I. Galkin, R. A. Cherkasov, and A. N. Pudovik
Kazan State University, Kazan, Tatarstan, Russia
Received June 28, 1999
Abstract For a series of phenyl-substituted N-isopropylbenzalimines, the effect of substituent on their
capability to add dimethyl hydrogen phosphite was studied qualitatively in the condensed phase (DTA) and
quantitatively (with determination of the kinetic and activation parameters) in 2-propanol solutions with
spectrophotometric monitoring of the reaction. A reaction mechanism was proposed, involving formation of
a highly organized four-membered transition state.
One of the main routes to -amino phosphonates is
the Pudovik reaction consisting in addition of dialkyl
hydrogen phosphites to compounds containing a C=N
bond [1]. Despite numerous publications on the syn-
thetic aspect of the Pudovik reaction and applications
of its products, kinetic data on this reaction are few
and sometimes contradictory. The first attempt to
quantitatively study this reaction, catalyzed with a
sodium alcoholate, was made by Pudovik and Kor-
chemkina [2]. They suggested a chain mechanism
involving formation of the dialkyl phosphite anion
followed by its attack of the electrophilic carbon atom
of the C=N bond. This mechanism was subsequently
supported in [3, 4]. Kinetic studies of the reactions
of azomethines with dialkyl hydrogen phosphites in
the presence of HCl [5, 6] led to a conclusion that
gen phosphite. On the contrary, our spectrophotomet-
ric study of the kinetics of addition of dialkyl hydro-
gen phosphites to 1-cyclohexylimino-2-butene in the
absence of catalysts led to a conclusion that the reac-
tion is nucleophilic [10]. The reaction is preceded
by fast formation of a complex (presumably from
dialkyl hydrogen phosphite and imine), as suggested
by a considerable bathochromic shift of the imine
absorption maximum. Subsequent transformation of
the complex into the reaction product is a monomo-
lecular process. Later we found [11] that the complex
is formed with the participation of hydrogen chloride
present in the initial dialkyl hydrogen phosphite as
impurity, despite repeated distillation. Therefore, in
the subsequent experiments dialkyl hydrogen phos-
phites were purified by adding a small amount of
the acid catalyst not only enhances the electrophilicity sodium metal prior to distillation. On mixing the reac-
of the azomethine carbon atom owing to protonation
of the nitrogen atom, but also increases the relative
content of the P(III) form of dialkyl hydrogen phos-
phonate, responsible, as believed in [5, 6], for the ad-
dition. However, the kinetic method chosen in [5, 6],
namely, alkali titration of unchanged dialkyl hydrogen
phosphite, seems to be unsuitable for obtaining reli-
tants, solvation complexes are formed, probably via
donor acceptor interactions of the phosphoryl group
rather than H bonding. The complex formation is re-
flected in the reaction kinetics.
The goal of this study was to elucidate the reaction
mechanism, with the reaction of dimethyl hydrogen
phosphite with a series of substituted N-isopropyl-
benzalimines (see below) as example.
1
able quantitative characteristics. A H NMR study of
the kinetics of -amino phosphonate formation in the
absence of catalysts [7 9] showed that this is a sec-
ond-order reaction. Introduction of electron-withdraw-
ing substituents into the benzene ring of both alde-
hyde and amine fragments decelerates the reaction.
Based on this result, an electrophilic mechanism was
proposed, involving initial protonation of the imine
nitrogen atom with the P(III) form of dialkyl hydro-
(MeO)2PHO +
CH NPr-i
Ia If
CH NHPr-i
R
R
O P(OMe)2
IIa IIf
R = 4-Me2N (a), 4-MeO (b), H (c), 4-Cl (d), 4-F (e),
3-NO2 (f).
1070-3632/02/7207-1067$27.00 2002 MAIK Nauka/Interperiodica

1068
SOBANOV et al.
Table 1. Yields, boiling points, refractive indices, and
relative densities of N-isopropylbenzalimines Ia If and
amino phosphonates IIa IIf
By workup of the contents of Stepanov vessels
after passing the exothermic maximum, we isolated
the corresponding amino phosphonates II; their yields
and constants are listed in Table 1.
Comp. Yield, bp, C ( p, mm Hg),
n2D0
d420
The structures of products II were confirmed by
NMR and IR spectroscopy. Their IR spectra contain
bands at 3270 [ (N H)], 1240 [ (P=O)], and 1030
no.
%
or mp, C
Ia
Ib
Ic
Id
Ie
If
IIa
IIb
IIc
IId
IIe
IIf
79
83
81
80
76
70
71
92
44
67
65
89
153 (8)
135 (16)
91 (18)
110 (12)
88 (15)
42
73
56
72
58
1.5940 0.9619
1.5440 0.9818
1.5262 0.9241
1.5442 1.0485
1.5070 0.9981
1
1060 [ (POC)] cm . The phosphorus chemical shift
in the 31P NMR spectra is about 25 ppm, which is
typical of phosphonates.
The trend in variation of the temperatures of the
endoeffects (Tmax) for the reactions of imines I with
dimethyl hydrogen phosphite clearly shows that the
reactivity tends to decrease on introducing electron-
withdrawing substituents into the aromatic ring of the
imines, which, at first glance, suggests the electrophil-
ic mechanism of the reaction involving the initial
proton transfer from dialkyl hydrogen phosphite to
the nitrogen atom. This result is nicely consistent with
the kinetic data obtained by 1H NMR [7 9]. However,
it is not quite correct to make definite conclusions on
the reaction mechanism from such data, because in the
absence of a solvent or at high concentrations of the
reactants the polarity of the medium and other factors
affecting the reaction rate appreciably change in going
from one reaction to another.
49
51
Table 2. Rate constants and activation parameters of the
reaction of N-isopropylbenzalimines Ia If with dimethyl
hydrogen phosphite in 2-propanol
1
k
102, l mol 1 s
H ,
kJ mol
S ,
1
1
J mol 1 K
25 C 35 C 45 C 55 C
Therefore, a quantitative study of this reaction was
performed in 2-propanol in the absence of catalyst.
The reaction was monitored spectrophotometrically
at 298 328 K. We found that the reaction has the total
second order (first order with respect to each of the
reactants). From the temperature dependence of the
rate constants, we determined the activation param-
eters (Table 2). The kinetic data show that, in going
from electron-donating to electron-withdrawing sub-
stituents in the aromatic ring of imines I, the rate
constant increases by an order of magnitude, which
suggests the nucleophilic mechanism of the addition.
Ia 0.058 0.113 0.212 0.342
Ib 0.176 0.308 0.584 1.027
45.6
45.2
40.7
28.7
25.5
17.6
153.1
145.2
144.8
184.5
195.0
222.2
Ic
1.110 2.161 3.672 5.491
Id 1.410 2.001 3.052 4.432
Ie
If
1.330 2.004 2.853 3.746
1.301 1.410 2.128 2.608
N-Isopropylbenzalimines I were prepared by con-
densation of the corresponding substituted benzalde-
hydes with isopropylamine. The composition and
structure of the imines were confirmed by elemental
analysis and by IR, NMR, and UV spectroscopy. The
IR spectra of these compounds contain bands at about
Considerable negative activation entropies, similar
to those obtained for the reaction with 1-cyclohexyl-
imino-2-butene [11], suggest that the reaction occurs
via a highly organized four-membered transition state:
1
1640 cm , characteristic of the C=N bond. The con-
stants of the imines are listed in Table 1.
The imines react with dimethyl hydrogen phosphite
on heating in the absence of catalyst to give the cor-
responding aminophosphonates II. The DTA curves
of equimolar mixtures of the reactants exhibit similar
exoeffects (their maxima are given below) assignable
to addition of dimethyl hydrogen phosphite across the
C=N bond:
(MeO)2PHO + Ar CH N R
Ar CH N R
.
.
.
.
.
.
.
Ar CH NH R
O P(MeO)2
(MeO)2P
O
H
In this transition state, the hydrogen atom acting
as an internal base loosens the P H bond and assists
the nucleophilic attack of the imine carbon atom by
the phosphorus atom.
Comp. no
Ia
Ib
Ic
Id
Ie
If
Tmax, C
80
89
93
93
95
109
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 7 2002

KINETICS AND MECHANISM OF THE PUDOVIK REACTION IN THE AZOMETHINE SERIES: I.
1069
Analysis of the compensation correlations between
the activation enthalpies, H , and entropies, S ,
shows that the experimental points form two different
straight lines, one of which corresponds to isopropyl-
benzalamine and imines containing electron-withdraw-
ing substituents, and the other, to imines with elec-
tron-donating substituents: p-methoxy and p-dimethyl-
amino groups. This fact suggests that the mechanisms
of the reactions with the substrates containing donor
and acceptor substituents in the aromatic ring have
certain specific features. We believe that these features
are related to certain geometric distortions of the
activated complex (within the framework of the com-
mon concerted mechanism with a four-membered
transition state) toward larger contribution of the
electrophilic assistance in the presence of donor sub-
stituents.
required temperature, we added 1 2 drops of a (2 3)
10 M solution of appropriate imine in 2-propanol.
2
After mixing, the spectrophotometric monitoring was
started. The pseudo-first-order rate constants were
calculated from the linear dependences of ln (D D )
on time. We monitored a decrease in the absorption
of imines at the following wavelengths (nm): Ia, 320;
Ib, 300; Ic, 278; Id, 292; Ie, 288; and If, 296. The
optical densities D were measured after the reaction
was a fortiori complete (1 day).
2-Propanol was pretreated as described in [13].
Dimethyl hydrogen phosphite was fractionated four
times in a flow of dry argon; the third fractionation
was performed with an addition of sodium metal to
remove HCl [11].
N-Isopropylbenzalimines I.
A
mixture of
0.042 mol of isopropylamine and 0.04 mol of sub-
stituted benzaldehyde was kept at room temperature
for 2 days and then fractionated several times in
a vacuum. The constants of the products are listed in
Table 1. N-Isopropyl-m-nitrobenzalimine If was re-
crystallized two times from 2-propanol. The purity
of the products was checked by IR spectroscopy and
TLC.
It should be noted that such geometric distortions
of the activated complex are typical of labile cyclic
structures; they were noted in numerous papers, e.g.,
for addition of hydroxy and amino phosphonates to
phenyl isocyanate [12].
In the subsequent paper, we will analyze in detail
our kinetic data and consider on the quantitative level
the reactivity of N-arylazomethines.
Thermographic studies were performed in sealed
Stepanov vessels on a custom-made installation using
a two-coordinate potentiometer and a linear heating
sensor. Mineral oil was the reference; the temperature
was monitored with a Chromel Alumel thermocouple;
Thus, the whole set of the results obtained unam-
biguously indicates that the reaction, on the whole,
occurs by the nucleophilic (with respect to the organo-
phosphorus reagent) mechanism via a four-membered
labile cyclic transition state whose geometry is very
sensitive to the electronic effects of substituents.
1
the heating rate was 4 5 deg min . A Stepanov ves-
sel was charged with 0.55 mg of an equimolar mixture
of dimethyl hydrogen phosphite and an imine. After
passing the exoeffect maximum, the recording was
stopped, and the mixture was recrystallized from hex-
ane with an addition of diethyl ether. The constants
and yields of the resulting amino phosphonates II are
listed in Table 1.
A certain inconsistency of the kinetic data with the
DTA data and data of [7 9] may be largely due to
appreciably different reaction media.
EXPERIMENTAL
The IR spectra were taken on a Specord IR-75
spectrophotometer (thin films or mulls in mineral oil),
and the 31P NMR spectra, on an RYa-2303 spectrom-
eter (8 MHz, external reference 85% H3PO4).
ACKNOWLEDGMENTS
The study was performed within the framework of
the scientific and technical program Russian Univer-
sities Basic Research and of joint program of
CRDF and Ministry of Education of the Russian
Federation Basic Research and Higher Education
(grant REC-007).
The TLC analysis was performed on Silufol UV-
254 plates, eluent hexane acetone, 1 : 1. The chroma-
tograms were developed by treatment with iodine
vapor.
The kinetics of the reactions of N-isopropylbenzal-
imines with dimethyl hydrogen phosphite were stud-
ied spectrophotometrically with an SF-46 spectropho-
tometer in temperature-controlled cells at 298 328 K.
Into a cell containing 3 ml of a 0.1 M solution of di-
methyl hydrogen phosphite in 2-propanol, kept at the
REFERENCES
1. Pudovik, A.N., Dokl. Akad. Nauk SSSR, 1952,
vol. 83, no. 6, p. 865.
2. Pudovik, A.N. and Korchemkina, M.V., Izv. Akad.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 7 2002

1070
SOBANOV et al.
9. Gartman, G.A., Pak, V.D., and Kozlov, N.S.,
Nauk SSSR, Otd. Khim. Nauk, 1952, no. 5, p. 940.
Zh. Obshch. Khim., 1979, vol. 49, no. 10, p. 2375.
3. Henderson, W.M. and Shelver, W.H., J. Pharm. Sci.,
1969, vol. 58, no. 1, p. 106.
4. Horkins, L.V., Vicik, L.P., and Sheller, M.N.,
10. Galkin, V.I., Bakhtiyarova, I.V., Sobanov, A.A., Cher-
kasov, R.A., and Pudovik, A.N., Dokl. Akad. Nauk
SSSR, 1985, vol. 285, no. 3, p. 634.
J. Pharm. Sci., 1972, vol. 61, no. 3, p. 1114.
11. Ovchinnikov, V.V., Sobanov, A.A., and Pudo-
vik, A.N., Dokl. Ross. Akad. Nauk, 1993, vol. 333,
no. 1, p. 48.
5. Kozlov, N.S., Pak, V.D., and Levashov, I.N., Dokl.
Akad. Nauk Bel. SSR, 1970, vol. 14, no. 3, p. 243.
6. Levashov, I.N., Kozlov, N.S., and Pak, V.D.,
Zh. Obshch. Khim., 1974, vol. 44, no. 5, p. 1112.
12. Sayakhov, R.D., Galkin, V.I., Cherkasov, R.A., Mi-
ronov, A.V., and Kutyrev, G.A., Zh. Obshch. Khim.,
1993, vol. 63, no. 11, p. 2476.
7. Pak, V.D., Kozlov, N.S., Balykova, I.A., and Gart-
man, G.A., Zh. Obshch. Khim., 1976, vol. 46, no. 3,
p. 497.
13. Gordon, A.J. and Ford, R.A., The Chemist’s Com-
panion. A Handbook of Practical Data, Techniques,
and References, New York: Wiley, 1972.
8. Gartman, G.A., Pak, V.D., and Kozlov, N.S.,
Zh. Obshch. Khim., 1978, vol. 48, no. 7, p. 1504.
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