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2
Tetrahedron
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active bis(aminophosphonate) and bis(aminophosphine oxide)
derivatives has not been described before.
of 71% after column chromatography. Carrying out the
condensation at 100 °C, a similar result was attained (Table
1/entry 4). Changing for diethyl phosphite, the reaction was
slower, at 80 °C after 30 min still 24% of the triazine (3) was
present that disappeared only after a reaction time of 40 min
giving the expected product 1b quantitatively (Table 1/entries 5
and 6). We also carried out a neat reaction at 100 °C which, after
20 min, afforded the diethyl α-aminophosphonate 1b in a yield of
77% (Table 1/entry 7). The condensation with dibutyl phosphite
was rather similar, furnishing the butyl aminophosphonate (1c) in
a quantitative conversion at 100 °C after 30 min, and in a yield of
80% (Table 1/entry 8).
In this paper, we introduce an efficient catalyst- and solvent-
free method for the synthesis of optically active α-
aminophosphonate derivatives involving the MW-assisted
Kabachnik-Fields condensations of (S)-phenylethylamine,
paraformaldehyde and various >P(O)H reagents, such as dialkyl
phosphites, ethyl phenyl-H-phosphinate or diphenylphosphine
oxide. We also aimed at the utilization of the bis(phosphine
oxide) in the synthesis of an optically active bidentate P-ligand
suitable in the preparation of a platinum complex.
2. Results and discussion
In the next series of experiments, two equivalents of both the
paraformaldehyde and the dialkyl phosphite were measured in
First,
the
Kabachnik-Fields
reaction
of
(S)-α-
aiming
at
the
synthesis
of
optically
active
phenylethylamine, paraformaldehyde and dialkyl phosphites was
studied under MW-assisted catalyst- and solvent-free conditions
(Table 1). During our experiments, we came across three
different species as the products, whose ratio depended on the
conditions employed. Beside the expected α-aminophosphonate
(1), the N-methylated α-aminophosphonate (2a) {δp (CDCl3)
bis(aminophosphonates) 4 (Table 2). In these experiments, the
expected bis(phosphonylmethyl)amines (4a-c) predominated, but
some of the mono aminophosphonates (1b and 1c) were also
formed. In the reaction of dimethyl phosphite at 80 °C for 1 h,
the reaction mixture contained 98% of bis-product 4a and 2% of
the
N-methylated
mono
aminophosphonate
(2a)
28.5, [M+H]+
= 258.1251, C12H21NO3P requires 258.1254},
found
and a triazine-type intermediate (3) {[M+H]+
= 400.2456,
(Table 2/entry 1). Isolated yield of the target compound (4a) was
84%. The reaction with diethyl phosphite was somewhat
incomplete at 100 °C after 1 h, but an irradiation of 1.1 h allowed
a full conversion (Table 2/entries 2 and 3). Compound 4b was
obtained in a yield of 83%. Dibutyl phosphite reacted
significantly slower. After a reaction time of 1 h at 100 °C, still
30% of the mono aminophosphonate (1c) was present. The
proportion of 1c decreased to 14% after a reaction time of 1.5 h.
(Table 2/entries 4 and 5). Complete conversion could be obtained
at 120 °C after 1.5 h (Table 2/entry 6). Product 4c was prepared
in a yield of 83%.
The experiences marked by Table 2/entries 2/3 and 4/5 suggest
that α-aminophosphonates 1b and 1c are the intermediates for
bis-products 4b and 4c, respectively.
Next, ethyl octyl phosphite and ethyl phenyl-H-phosphinate
were applied in the condensation with 1 equivalent of
paraformaldehyde and α-phenylethylamine (Scheme 1, Table 3).
found
1
C27H34N3 requires 400.2753, H NMR data is provided in Exp.
section and SM} could also be observed. It is noted that over-
methylated products were also formed in other instances.28,29,39
The reaction of dialkyl phosphites with the in situ formed 1,3,5-
tris((S)-α-phenylethyl)-1,3,5-triazine (3) also led to the desired
products (1). Measuring in the three components including
dimethyl phosphite in an equimolar quantity, and performing the
irradiation at 40 °C for 1 h, the mixture comprised 55% of the
1,3,5-tris((S)-α-phenylethyl)-1,3,5-triazine (3) and 4% of the
methylated
by-product
(2a)
beside
the
expected
α-aminophosphonate (1a) representing 41% (Table1/entry 1).
Repeating the experiment at 80 °C for 10 min, the ratio of
compounds 1a, 2a and 3 was 58:6:36 (Table 1/entry 2). After
20 min, only product 1a and by-product 2a were present in the
mixture in a proportion of 91:9 (Table 1/entry 3). The optically
active dimethyl α-aminophosphonate 1a was isolated in a yield
Table 1 Synthesis of dialkyl-(S)-α-phenylethylaminomethylphosphonates (1)
Product composition
Yield of 1
[%]a,b
T
t
Entry
R
[°C]
[min]
[%]c
1
2
4
3
55
36
0
1
Me
Me
Me
Me
Et
40
80
60
10
20
10
30
40
20
30
41
–
–
2
58
6
3
80
91
9
71 (1a)
–
4
100
80
89
11
–
0
5
76
24
0
–
6
Et
80
100
100
100
–
75 (1b)
77 (1b)
80 (1c)
7
Et
100
100
–
0
8
Bu
–
0
aBased on GC.
bAverage of 2-3 parallel reactions.
cAfter column chromatography.
Bálint, Erika
