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A simple route to chiral phosphonothionates from diastereomeric phosphonamidothionates
Tetdedmn
B.S.
Purnmand*. Defence
Gnalfor-474DD2
Optical
AbBmCt: catalyzed
of
isomers
alcoholysis
organic
and
available
to-date
resolved
phosphonothioic
phenols5.
for
However,
yields.
this
Recently
preparation
of
considered
for
the P-N
cyanofenphos
(O-ethyl,
compounds Reported
us
to
examine
benzylamine
of
their
into
method
bond
multisteps knowledge
insecticides. for
pharyl
provided
reaction
with
good
optically
+
and
bond
find
only
through
with
affords
pocr
was
methodology
this
communication of
phosphonothionate)
pure an
of
reaction
consequently
this
in
procedure
conversion
by
acid
and
application
The
cleavage
active
of
intermediates isomers
R[+)
adopted
has
never
the
for been
utility
of
enantiomers
of
insecticide
and
led.
This
and S(-)-
prompted a
-methyl
1).
H2NCH(CH3)C6H5
35’C,
6h
s
OR
II/ C6H5 -P \
‘Cl 1
toxicity1
followed
synthesis
yield
Dlcydoc!;!~mine i/OR C6H5 -P
In
the
is
by purity.
described.
procedure’
2 (eq.
of
cleavage
compounds
compounds
P-N
prepared optical
differential
chlorides
and
our
0-4-cyanophseyl
are
the
P-O
been in high
mechanisms3*4.
these
Involves To
these
reaction
acids
esters’.
have
exhibit
Moreover,
preparation
synthesis
stereospecific related
compounds,
stereoselective chiral
India
phosphonamidothlonates
enzymatic
the
Establishment
phosphcmothlonates
of resolved
Chlral organophoephorus 2 metabolism in living organisms. elucidating
and G.Lal
Batra
and Development
Research
Lefters. Vol. 35. l’kt. 26, pp. 4641-s 1994 meiert4I%aceLtd ?Yiatedint3rutBlit8iQ oo404Q39/94 s7.oo+o.oo
3
2 U : R=4-CN-CgH4,
b
: R=4-Cl-C6H4, 4641
c : R=C6H5
ieq. NHCH(CH3)C6H5
11
4642
The
following
procedure
phosphonamidothionate containing (2.49.
dry
benzene
2Ommol) and
The resction
(8:2)
up
. This
the sides
241 end
percent
of flask
of
through
specific
3b,
c
rotation
Acid
with was
stereospecific
s
ia
done
as In a
isomers
with
Jeol
solid
was
above. manner
ether
of
38-c
es represented
evidence
The
synthesis was
in
of
obtained IR. ‘H
Physical
data
1. products’
4e-e
Stirred
H2S04(10:3, at 45’C.
V/VI c6HS
5h
II/ - ‘\
1C6H5
(eq. 2) -OR’
4
for
high
atereospeciflcity
was brought by comparing observed 4a-e were characterized by IR and
Products reported valuesa. 10 data and specific data . Physical
specific rotation 1 H NMR spectral
cyanofenphos,
the
reacting
.2).
3
in table
hundred
by
S PR R’OHKonc.
‘NH CH ( CH3
given
polarimeter
showed
fn table
OR
v %% -p,
An
Elmer
Microsnalysis.
resulted (eq
which
6 . 28% yield).
the producta8.
3e-c are summarized
viscous
overnight
resolution
(40-60%).
to characterize
formed
so obtained
obtained
Though the
stirring.
83% yield ) as aside
Perkln
2
benzene/hexane
RX90 respectively
described
of
thus
liquid
3e (1.5
P(+)C(+)
similar
with
elusnt:
(6.3 9,
P NMR by
Isomer
methsnolyaia/ethanolyaia P-N bond cleavage
(50 ml).
and kept
cystalline
in petroleum was used
gel 3’
31
S(-)-isomer
of
6 h and DCHA salt
(10:3)
model
solution
phenyl in a flask
taken
and the residual
afforded
end
qmol)
benzene
on silica
P(-)C(-).
of resolved
catalyzed
vacuum
white
rotation
fractional crystallization 31P NMR spectroscopy
and specific
through
gave
of diastereomer of
in dry
in hexane/ether
R(+)- a -methylbenzylamine
NMR and
fractions
a
for another
under
90 MHz spectrometer
purity
diaatereomer
2Dmmol)
0-4-cyanophenyl
(6.06.20
slowly
ChtUmstOgt%phy
dissolved
Determination model
added
was removed
column
of
To la
et 35V
‘of collected
was
upon rubbing
wee
was stirred
by
Bvaporstlon
liquid
(5Oml)
Solvent
cleaned
preparation
iOr
representative.
DCHA (3.69..
mixture
was filtered. was
3 is
with
rotation
of ensntiomers
4a+
are
1.
present
method
an important
thus
provided
neurotoxic
esterase
an
easy
inhibitor.
access
to
chiral
isomers
of
4643
Table
Q -retLylbrrtyl)photpbonemidotkioeete
II-(
1.
I
Prodect
yield
HO.
DIestoreo8er
llOi~CIll8rFormula
(II
4-ct1-c6H,
38
4-Cl-C6H4
3b
3c
‘6’5
Table
2,
DptWally
P(+)C(+)
+36.45
89-90
c21H19N2*pS
28
P(-)C(-)
-3b.SO
89-90
(378.43)
27
P(+)C(+)
+46.80
87-88
C20H,9NOPSCl
24
Pf-)e(;l
-47.00
87-88
(387.85)
25
Pf+fC(+I
r5s.40
84-85
C
27
P(-)C(-1
-58.60
84-85
(353.42)
Active
R
Product
26
RI
Pbotphonothlorater
Y lcld
UO.
4-CN-C6H4
C2HS
a I 2ao
*P
(c=4.c*c13)
*C
C
(II
4r
20H20W~PS
(R):+37.7
63
lolcculer For~ulr
loo-101
C15”14W02PS (303.31)
[33*5,c=4.0]3 66
(S):-38.1
60
(R):+46.7
58
(S):-45.8 (R):+29.3
(-33.7.c-3*0)3 4-CN-C6H4
4b
CH
3
4c
4-Cl-C6H4
C2H5
57 60
(S):-29.4
id
4-C1-CsR4
CH3
64
(1):*37.8
4e
‘6R5
cB3
65
fS):-38.1
54
(R):+Pf.t
56
(S):-27.7
60-61
Rata
under We
advise
and
K hanwil
Km kar
C,4H,402PSC1
Lfquid
C
13&13 (299.73)
Liquid
0
2
PSCl
C13”1302PS (264.28)
-----ml__
rotations
Acknorledgemcnt. valuable
Liquid
(312.75)
-----I------
3 Specific
C14H12N02PS (289.29)
for
are
through
Hawta
Pandey
secretarial
parentheses thankful out
to
this for
are Or
work. provtdlng
assistance.
reported R.Y. We the
--_-
values.
Swaey, also
thank
analytical
Dlrector. to and
DRDE,
Mr.
kteehfr
spectral
Gwalior Palit, data
for Hr
and
his Lakhi
kir.6.R.
References
Ohkawa.
2.
Ohkawa.
il.; M1kaml.N.; il.;
Agric. 3.
notes:
and
1.
5.;
Jpn.,
Chcm.Soc.
Ohkawa.
ii.; Mikami.
4.
Oonninger.
5.
Al1ahyari.R.; Fukuto,
T.R.
6.
Otsuki.
T.;
C.
J.
Agric.
7.
Purnartand;
gatra.
Sa:IR(KBr)
3360.
3.7(t.lH, CDC13):
675.2;
Chen
Ind.
J.
Agric.
J.
Biol.
R.L.;. 28.
1980.
1978,
42.
Abstr.
445-450
Pap.
Natl.
Meet.
41.
369-376.
Chen,
1992,
NMR
Ti~m.
cm ";'H
316,
Hz),
4.51
(m,
51.46(d.3H.
Found:
7.05-8.01
61.93;
H,
NMR
C.67.04;
(br,m.
4.94;
5x6.49
14H);"P
N,
516.83
14H),
3.61
Hzj,
(90HHz,
H.S.OB;N,7.13
(90Mi4z,COC13~61.47(d,3ii~
lH,NH), C.
R.A.;
779-779.
(90NHz,COC13): 7.07-B.Ol(br.m
NHR
Jacobson.
E.;
1991*.811-813.
Calcd:C.66.65;H,5.06;N,7.40 1200
Chen.1977
594-599.
Synthesis,
4.58(m,lH,NH).
Anl.Calcd:
Chem.
265-268
Lapp.
2240,1225cm-';'H
Anal.
676.61;
44,
J-6;
3300.
(t,lH,J=9.40 COC13):
1971.
Food
B.S.
8101.
Wiyamote.
J.
Y.;Sakurai.H.
J=9.74Hz),
(KBr)
1.;
Hiyamoto.
Y.H.O.
Agric.
545.
Hollingshaus.
Okamotr.
J.
Mikari.
1980, N.;
Bull.
8.
3b:IR
Miyanoto.
Kogiso.
31P
Found:
Hz).
NWR
3.53
(90MHz,
C.61.90;H,4.95;
N.3.28 3c
:IR
(KBr)3300.
3.53(t.
67.70; 4a:
diluted
diastereoner
with
with
was
water
purified
(8:2).
m.p.
4a:
(KBr)
Hx);
4.24 4d:
IR
(m,2H), IR
(KBr)
7.13-8.01 IR(KBr)
(90NHz.CDC13):
Anal
7.00 C.67.97;
Calcd:
61.43
(d,3H.J=6.89Hz),
-8.01
15H);31P
(br.m.
H.5.70;N.3.96.
Found
:
C,
IR(KBr)
7.01-8.11
of
3a
H2S04
(201111) and layer (each
was
of
v/v)
was
chromatography
solvent
under
was
45OC
with
washed
Ether
mmol)
at
extracted first
lOm1).
column
1.05
(0.49.
(lo:3
for
two
with
3%
reduced
of
NaHC03
silica
off
and
the
using
yielded
a
mixture
mixture
3Oml
solution
gel
pressure
with
Reaction
portions
evaporated on
stirred 5h.
each
was with
(101111) and
crude
product
benzene/hexane 4e
(0.21
9.663
lOO-10l°C. 2230,1215,1040cm
-';'H
NHR
(90MHz,CDC13~
61.37(t.3H,J=7.lHz).
7.14-8.05(br.m.9H) 2230,1220,1050cm
-1
;
'H
NMR
(90MHz.CDC13):
63.85
(d,JH,J=14.18
(br.m,SH) 1210.
(m.2H). IR(KBr)
7.03-8.11 4c:
by
Evaporation
yield)
4c:
water Ether
ether.
twice
4.28
NMR
4.5l(m.lH.NH);
Hz).
673.98;
ethanol/Cone.
of
ethyl
4b:
'H
H.5.55;N.3.47
P(-)C(-)
(2Oml)
10.
cm-'
519.79
1H.
NHR(90NHz.COC13):
9
1200
1035cm-';
7.00-8.12 1210.
'ii
(br.m.9H) -1 1 H ;
104Ocm
NMR(90MHz.CDC13):
NMR(90MHz.
COC13):
61.42
63.82
(t.3H,
(d
3H.
J=7.05Hz).
J513.85Hz).
(br,m,PH) 1200,
104Ocm.';
'H
NRR
(br.m.lOH)
(Received in UK 15 April 1994, accepted 29 April 1994)
(90MHr,CDC13):
63.82(d.3H.J=12.92Hz).
B.S.
Purnmand*. Defence
Gnalfor-474DD2
Optical
AbBmCt: catalyzed
of
isomers
alcoholysis
organic
and
available
to-date
resolved
phosphonothioic
phenols5.
for
However,
yields.
this
Recently
preparation
of
considered
for
the P-N
cyanofenphos
(O-ethyl,
compounds Reported
us
to
examine
benzylamine
of
their
into
method
bond
multisteps knowledge
insecticides. for
pharyl
provided
reaction
with
good
optically
+
and
bond
find
only
through
with
affords
pocr
was
methodology
this
communication of
phosphonothionate)
pure an
of
reaction
consequently
this
in
procedure
conversion
by
acid
and
application
The
cleavage
active
of
intermediates isomers
R[+)
adopted
has
never
the
for been
utility
of
enantiomers
of
insecticide
and
led.
This
and S(-)-
prompted a
-methyl
1).
H2NCH(CH3)C6H5
35’C,
6h
s
OR
II/ C6H5 -P \
‘Cl 1
toxicity1
followed
synthesis
yield
Dlcydoc!;!~mine i/OR C6H5 -P
In
the
is
by purity.
described.
procedure’
2 (eq.
of
cleavage
compounds
compounds
P-N
prepared optical
differential
chlorides
and
our
0-4-cyanophseyl
are
the
P-O
been in high
mechanisms3*4.
these
Involves To
these
reaction
acids
esters’.
have
exhibit
Moreover,
preparation
synthesis
stereospecific related
compounds,
stereoselective chiral
India
phosphonamidothlonates
enzymatic
the
Establishment
phosphcmothlonates
of resolved
Chlral organophoephorus 2 metabolism in living organisms. elucidating
and G.Lal
Batra
and Development
Research
Lefters. Vol. 35. l’kt. 26, pp. 4641-s 1994 meiert4I%aceLtd ?Yiatedint3rutBlit8iQ oo404Q39/94 s7.oo+o.oo
3
2 U : R=4-CN-CgH4,
b
: R=4-Cl-C6H4, 4641
c : R=C6H5
ieq. NHCH(CH3)C6H5
11
4642
The
following
procedure
phosphonamidothionate containing (2.49.
dry
benzene
2Ommol) and
The resction
(8:2)
up
. This
the sides
241 end
percent
of flask
of
through
specific
3b,
c
rotation
Acid
with was
stereospecific
s
ia
done
as In a
isomers
with
Jeol
solid
was
above. manner
ether
of
38-c
es represented
evidence
The
synthesis was
in
of
obtained IR. ‘H
Physical
data
1. products’
4e-e
Stirred
H2S04(10:3, at 45’C.
V/VI c6HS
5h
II/ - ‘\
1C6H5
(eq. 2) -OR’
4
for
high
atereospeciflcity
was brought by comparing observed 4a-e were characterized by IR and
Products reported valuesa. 10 data and specific data . Physical
specific rotation 1 H NMR spectral
cyanofenphos,
the
reacting
.2).
3
in table
hundred
by
S PR R’OHKonc.
‘NH CH ( CH3
given
polarimeter
showed
fn table
OR
v %% -p,
An
Elmer
Microsnalysis.
resulted (eq
which
6 . 28% yield).
the producta8.
3e-c are summarized
viscous
overnight
resolution
(40-60%).
to characterize
formed
so obtained
obtained
Though the
stirring.
83% yield ) as aside
Perkln
2
benzene/hexane
RX90 respectively
described
of
thus
liquid
3e (1.5
P(+)C(+)
similar
with
elusnt:
(6.3 9,
P NMR by
Isomer
methsnolyaia/ethanolyaia P-N bond cleavage
(50 ml).
and kept
cystalline
in petroleum was used
gel 3’
31
S(-)-isomer
of
6 h and DCHA salt
(10:3)
model
solution
phenyl in a flask
taken
and the residual
afforded
end
qmol)
benzene
on silica
P(-)C(-).
of resolved
catalyzed
vacuum
white
rotation
fractional crystallization 31P NMR spectroscopy
and specific
through
gave
of diastereomer of
in dry
in hexane/ether
R(+)- a -methylbenzylamine
NMR and
fractions
a
for another
under
90 MHz spectrometer
purity
diaatereomer
2Dmmol)
0-4-cyanophenyl
(6.06.20
slowly
ChtUmstOgt%phy
dissolved
Determination model
added
was removed
column
of
To la
et 35V
‘of collected
was
upon rubbing
wee
was stirred
by
Bvaporstlon
liquid
(5Oml)
Solvent
cleaned
preparation
iOr
representative.
DCHA (3.69..
mixture
was filtered. was
3 is
with
rotation
of ensntiomers
4a+
are
1.
present
method
an important
thus
provided
neurotoxic
esterase
an
easy
inhibitor.
access
to
chiral
isomers
of
4643
Table
Q -retLylbrrtyl)photpbonemidotkioeete
II-(
1.
I
Prodect
yield
HO.
DIestoreo8er
llOi~CIll8rFormula
(II
4-ct1-c6H,
38
4-Cl-C6H4
3b
3c
‘6’5
Table
2,
DptWally
P(+)C(+)
+36.45
89-90
c21H19N2*pS
28
P(-)C(-)
-3b.SO
89-90
(378.43)
27
P(+)C(+)
+46.80
87-88
C20H,9NOPSCl
24
Pf-)e(;l
-47.00
87-88
(387.85)
25
Pf+fC(+I
r5s.40
84-85
C
27
P(-)C(-1
-58.60
84-85
(353.42)
Active
R
Product
26
RI
Pbotphonothlorater
Y lcld
UO.
4-CN-C6H4
C2HS
a I 2ao
*P
(c=4.c*c13)
*C
C
(II
4r
20H20W~PS
(R):+37.7
63
lolcculer For~ulr
loo-101
C15”14W02PS (303.31)
[33*5,c=4.0]3 66
(S):-38.1
60
(R):+46.7
58
(S):-45.8 (R):+29.3
(-33.7.c-3*0)3 4-CN-C6H4
4b
CH
3
4c
4-Cl-C6H4
C2H5
57 60
(S):-29.4
id
4-C1-CsR4
CH3
64
(1):*37.8
4e
‘6R5
cB3
65
fS):-38.1
54
(R):+Pf.t
56
(S):-27.7
60-61
Rata
under We
advise
and
K hanwil
Km kar
C,4H,402PSC1
Lfquid
C
13&13 (299.73)
Liquid
0
2
PSCl
C13”1302PS (264.28)
-----ml__
rotations
Acknorledgemcnt. valuable
Liquid
(312.75)
-----I------
3 Specific
C14H12N02PS (289.29)
for
are
through
Hawta
Pandey
secretarial
parentheses thankful out
to
this for
are Or
work. provtdlng
assistance.
reported R.Y. We the
--_-
values.
Swaey, also
thank
analytical
Dlrector. to and
DRDE,
Mr.
kteehfr
spectral
Gwalior Palit, data
for Hr
and
his Lakhi
kir.6.R.
References
Ohkawa.
2.
Ohkawa.
il.; M1kaml.N.; il.;
Agric. 3.
notes:
and
1.
5.;
Jpn.,
Chcm.Soc.
Ohkawa.
ii.; Mikami.
4.
Oonninger.
5.
Al1ahyari.R.; Fukuto,
T.R.
6.
Otsuki.
T.;
C.
J.
Agric.
7.
Purnartand;
gatra.
Sa:IR(KBr)
3360.
3.7(t.lH, CDC13):
675.2;
Chen
Ind.
J.
Agric.
J.
Biol.
R.L.;. 28.
1980.
1978,
42.
Abstr.
445-450
Pap.
Natl.
Meet.
41.
369-376.
Chen,
1992,
NMR
Ti~m.
cm ";'H
316,
Hz),
4.51
(m,
51.46(d.3H.
Found:
7.05-8.01
61.93;
H,
NMR
C.67.04;
(br,m.
4.94;
5x6.49
14H);"P
N,
516.83
14H),
3.61
Hzj,
(90HHz,
H.S.OB;N,7.13
(90Mi4z,COC13~61.47(d,3ii~
lH,NH), C.
R.A.;
779-779.
(90NHz,COC13): 7.07-B.Ol(br.m
NHR
Jacobson.
E.;
1991*.811-813.
Calcd:C.66.65;H,5.06;N,7.40 1200
Chen.1977
594-599.
Synthesis,
4.58(m,lH,NH).
Anl.Calcd:
Chem.
265-268
Lapp.
2240,1225cm-';'H
Anal.
676.61;
44,
J-6;
3300.
(t,lH,J=9.40 COC13):
1971.
Food
B.S.
8101.
Wiyamote.
J.
Y.;Sakurai.H.
J=9.74Hz),
(KBr)
1.;
Hiyamoto.
Y.H.O.
Agric.
545.
Hollingshaus.
Okamotr.
J.
Mikari.
1980, N.;
Bull.
8.
3b:IR
Miyanoto.
Kogiso.
31P
Found:
Hz).
NWR
3.53
(90MHz,
C.61.90;H,4.95;
N.3.28 3c
:IR
(KBr)3300.
3.53(t.
67.70; 4a:
diluted
diastereoner
with
with
was
water
purified
(8:2).
m.p.
4a:
(KBr)
Hx);
4.24 4d:
IR
(m,2H), IR
(KBr)
7.13-8.01 IR(KBr)
(90NHz.CDC13):
Anal
7.00 C.67.97;
Calcd:
61.43
(d,3H.J=6.89Hz),
-8.01
15H);31P
(br.m.
H.5.70;N.3.96.
Found
:
C,
IR(KBr)
7.01-8.11
of
3a
H2S04
(201111) and layer (each
was
of
v/v)
was
chromatography
solvent
under
was
45OC
with
washed
Ether
mmol)
at
extracted first
lOm1).
column
1.05
(0.49.
(lo:3
for
two
with
3%
reduced
of
NaHC03
silica
off
and
the
using
yielded
a
mixture
mixture
3Oml
solution
gel
pressure
with
Reaction
portions
evaporated on
stirred 5h.
each
was with
(101111) and
crude
product
benzene/hexane 4e
(0.21
9.663
lOO-10l°C. 2230,1215,1040cm
-';'H
NHR
(90MHz,CDC13~
61.37(t.3H,J=7.lHz).
7.14-8.05(br.m.9H) 2230,1220,1050cm
-1
;
'H
NMR
(90MHz.CDC13):
63.85
(d,JH,J=14.18
(br.m,SH) 1210.
(m.2H). IR(KBr)
7.03-8.11 4c:
by
Evaporation
yield)
4c:
water Ether
ether.
twice
4.28
NMR
4.5l(m.lH.NH);
Hz).
673.98;
ethanol/Cone.
of
ethyl
4b:
'H
H.5.55;N.3.47
P(-)C(-)
(2Oml)
10.
cm-'
519.79
1H.
NHR(90NHz.COC13):
9
1200
1035cm-';
7.00-8.12 1210.
'ii
(br.m.9H) -1 1 H ;
104Ocm
NMR(90MHz.CDC13):
NMR(90MHz.
COC13):
61.42
63.82
(t.3H,
(d
3H.
J=7.05Hz).
J513.85Hz).
(br,m,PH) 1200,
104Ocm.';
'H
NRR
(br.m.lOH)
(Received in UK 15 April 1994, accepted 29 April 1994)
(90MHr,CDC13):
63.82(d.3H.J=12.92Hz).