98 Huang and Chen
RESULTS AND DISCUSSION
Synthesis of the Products
aldehydes, benzyl carbamate, and triphenyl phos-
phite as shown in Scheme 3 [15]. Compound 1 re-
acted smoothly with bis(trichloromethyl) carbonate
with the help of four molar equivalents of triethyl-
amine to give isocyanates 2 that then formed the title
compounds by the addition with 3. We could trans-
form 1 into the corresponding diphenyl ␣-amino-
phosphonates by the reaction of ammonia in dry
benzene; nevertheless, our experiment revealed that
the yields could not be increased further by the one-
pot reaction of diphenyl ␣-aminophosphonates in-
stead of 1 under the same condition.
Efficient methodologies for forming the bond con-
necting the carbonyl and the phosphoryl groups are
available in the arsenal of the synthetic chemist
[1,11]. However, to the best of our knowledge, there
is no general method to synthesize the ␣-ketophos-
phondiamidates under mild conditions. We herein
wish to report a simple and direct method utilizing
the addition reaction of the phosphorus reagent con-
taining a P–H bond with isocyanates that were pre-
pared in a one-pot procedure from amines by the
action of triphosgene [bis(trichloromethyl) carbon-
ate]. Generally, these reactions are carried out under
base-catalyzed conditions. Isocyanates are usually
prepared by phosgene gas, which requires the haz-
ards of handling of phosgene and drastic conditions.
An improved method for the preparation of isocyan-
ates involves the use of triphosgene that is a safe and
stable replacement for phosgene [12]. The title com-
pounds were synthesized by a convenient one-pot
procedure, as shown in Scheme 1, in which the ap-
pearance of isocyanates 2 and the reaction terminal
point were monitored by IR spectroscopy.
The Structures of the Products
The structures of all of the title compounds were
confirmed by 1H NMR, 31P NMR, IR spectra, and el-
emental analyses. Their physical constants are listed
1
in Table 1, and data of the H NMR, 31P NMR, and
IR spectra are listed in Table 2 and Table 3.
The title compound 4 may be discussed by rec-
ognition of the presence of two chiral centers, for
example, CH and P, and consequently existence of
two pair of enantiomers (a pair of diastereoisomers)
31P NMR spectra (Table 3) exhibited doublets of the
chiral P in the range of d 3.1–4.3 accounting for the
pair of diastereoisomers, while 3 gave a single peak
at d 5.31 due to the presence of only one chiral phos-
phorus center. The separation of the diastereoiso-
mers was not successful by the column chromatog-
raphy method. The two diastereoisomers of
compound 4a were separated by partial recrystalli-
zation, and their 31P NMR data were determined as
d 3.33, 16.83, and d 4.25, 16.83 respectively. There is
no 31P–31P coupling between the two phosphorus at-
oms in the title compounds. The ratios of diaster-
eoisomers given in Table 3 were determined by in-
tegration of suitable signals in the 31P NMR spectra
of the crude products, which show that, unfortu-
nately, the synthetic reactions are not significantly
The intermediate 3, 1-ethoxycarbonylmethyl-
3-ethyl-2,3-dihydro-1,3,2-benzodiazaphosphorin-4
(1H)-one 2-oxide was prepared according to litera-
ture methods [13,14] by the multistep route outlined
in Scheme 2. The corresponding data of 3 are given
1
as following: 62% overall yield, m.p. 75–77ЊC. H
NMR (CDCl3, ppm; J, Hz): 1.22–1.36 (m, 6H,
2CH2CH3); 3.79 (m, 2H, NCH2CH3); 4.09–4.28 (m,
3H, 1/2NCH2CO2CH2CH3 ם
CO2CH2CH3); 4.74 (dd,
1H, 1/2PNCH2CO2Et, 3JPH ס
8.7, 2JHH ס
18.3); 6.60–
8.22 (m, 4H, C6H4); 7.95 (d, 1H, P(O)H, 1JPH ס
649.8).
31P NMR (CDCl3, ppm): 5.31 (s). Anal. calcd. for
C13H17N2O4P: C, 52.70; H, 5.78; N, 9.46. Found: C,
52.72; H, 5.84; N, 9.53.
Preparation of the hydrobromides of ␣-amino-
phosphonates 1 was readily accomplished in a two-
step sequence (45–80% overall yield) starting from
1
stereoselective in affording the products. In the H
SCHEME 1
SCHEME 2
Huang, Junmin
