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Stereochemistry of the reaction of ammonia with diethyl bromofumarate and diethyl bromomaleate
Tetrahedron Letters
No.7,
ppa 873-876,
Pergamon
1968.
Press.
Printed
in
Great
Britain.
STEREOCHEMISTRY OF THE REACTION OF AMMONIA WITH DIETHYL BROMOFDMARATE AND DIETHYL BROt40MALRATE1 K. D. Berlin, Department of
Lenton G. Williams‘ and 0. C. Dermer Chemistry, Oklahoma State University Stillwater, Oklahoma
(Received
Very
few
esters
have
An old
report3
been
of
that
amount.s, n
diethyl the
as
were
1967)
cr-bromo-cu,p-unsaturated of
reactions
dibromosuccinate
reaction
aziridine
and none
with
stereochemistry
and diethyl
identified
in minor
The
reinvestigated
bromofumarate
products,
ammonia
recorded.
indicates
We have diethyl
reactions
in USA Q9 September
of
with
bromomaleate.
Each
II
III.
isolated.
carboxylic
such
been
esters
and ethanolic
ammonia
and enamine
of
and cu,t+dibromo
diethyl
of
the
ammonia
meso-
four
isomers
of
gave
II
were
CH3CH202C .
steric
more of
requirements
stable
enamine
an cY,A-dibromo
bromide.4’5 the
of
immediately
indicates
that
yields
II
because Cromwell4
the
-cis
the
III the -cis has
It
compound
with
ammonia
probable
reaction
and _threo
esters
cannot
II
enamine
of
give
and no -cis
w
formed .
aziridine
bromide or
m
ervthro
into
aziridine
is
1 shows
displacement
hydrogen
the
carbonyl
Scheme
mixture
molecular
III
transition
the
and
bromide
the
trans
The
ester
enamine,and
and no -cis and -trans
postulated
the
vinylic type
with
agreed
sequence
form
prevent
that
the
the -cis
/
\ NH2
m
by trans
formation give
intermediate
873
the
of
the
first
step
our
form
work.
since can
ervthro
The
the
react or
trans
form
can II
elimination an enol
formation
in
and the
the
reaction
to
a vinylic
composition
components by two
of
collapse
routes:
intra-
elimination produce
of
the trans
and
displacement
same products in
creation
in
aziridine
intramolecular
its
dehydrohalogenation
azfridine, the
only
apparently
C=C/COZCH2CH3
is
be determined
isomer
bromides
cis
and amines
of
The
of
the
Conversely
three
but
but
III
The three
yield
formation
aziridine.
this
III.
to
reacts
of
generally
enamine.
enamine. erythro
ion
state is
formed,
II
of
I.
same two
were
expected
‘H
CH3CH202E.’ the
aziridine
the
some amides
\ H-
yield
unknown.
and a-dibromosuccinate,
esters
Undoubtedly
--Cis/trans
has
acid
of of
bromide
hydrogen
intermediate in about of -cis
to
bromide
seems the
yield
necessary
same ratio.
and -trans
ethylen-
No.7
875
No.7
imine
Experimental
ketones.
from 1,4-addition
en01 resulting
in the intermediate our case
steric
reaction
species
IR analysis carbonyl
of III
ketone
a brosd
signal
state
the most favored indicates
typical
leading
to the -cis
hydrogen
A singlet
are observed.
ratios.
asiridine
of groups
Apparently causes
in
the
III.
bonding 7
of the
and interactions
to form trans
groups.
conformation
product
of such compounds.
ethyl
(amine protons)
sizes
cisftrans
intramolecular
due to non-equivalent
at 6 6.59
relative
conformation
strong
group and the amine protons,
CDC13 shows peaks
is a most favored
can explain
in the transition
to take
there
of an amine and that
crCbromo-S-amino
hindrance
suggests
evidence’
between an ester
The NMR spectrum
at 6 5.45
Ensmine III
(vinyl
resisted
of III
proton)
all
in and
acylation
attempts. Aziridine
The IR spectrum
analysis. of II 2.84
II was identified
showed peaks (ring
to steric
ethsnolic
could
readily
g-Dnsubstituted derivatives,
which 9
the eeiridines. gave only
diethyl
aziridines lose
fumerate.
indicating
that
dilute
reaction
proceeds
perchloric
to authentic
acid
with
inversion
and subsequent
DL-erythro-R-hydroxysspartic
that
similar
and 6
stereochemistry
II was trans
8
With II
to those
owing
and
reported.
yield
the &nitroso
of the same stereochemistry
and triethylamine
-60°
in ether
as
at -60’
structure. ‘t
F02C2H5
?=F H5C202C
to 25’
H
‘+I
acid
and is highly hydrolysis acid
indicate
compounds.
-N20
dilute
acid
alkenes
chloride
7,
The NMR spectrum
(amine proton)
at low temperatures
II has the trans
,*’ H5C202C with
to
-cis
under conditions
H2C202C H*. H *’ &
of asiridines
at 6 1.85
IR and lMR
a-1-substituted-2,3-dibenzylaziridines
to yield
nitrosyl
data,
amine).
The assumption
chloride
of II with
ether -60’ Many cleavages
nftrosyl
Treatment
(C2H5j3N
(sec.
to the corresponding
N20 stereospecifically
NOCl
II
This
with
since
occurred
analytical
was insufficient
one isomer.
not be justified
no reaction
behavior,
and singlets
alone
only
by sodilmr ethoxide
sodium ethoxide,
groups
evidence
we had obtained
requirements
of chemical
band et 3280 cm.-’
ethyl
Spectroscopic
since
are epimerized
showed a single
due to equivalent
protons).
of the asiridine
on the basis
to yield
vicinal
stereospecific.
amino alcohols lob
Treatment
gave a compound identicsl
hydrochloride.
are known.
10
of II iith in IR spectrum
No.7
876
II
1. HCLOh, 80'
amino ester
2. NaHC03
HC1,80° 10 hrs.
Thus II has the trans structure.
Steric requirements are probably
sufficient in the
transition state leading to the -cis isomer of II to prevent its formation.
Only the aziridines
and enamines corresponding to II and III were obtained by treatment of dimethyl and di-g-propyl bromofumarate and dimethyl bromomaleate with ammonia in the corresponding alcohol. II could be N-acylated
Aziridine
in good yield with carboxylic acid chlorides and triethylamine.
talline products were obtained with 2,4_dichlorophenylacetyl
Crys-
chloride and E-nitrobenzoyl
chloride. When II was heated at 125' for 1.5 hours, it was converted almost quantitatively to III, which evidently has the greater stabi!ity. References: 1.
We gratefully acknowledge partial support by the Research Foundation in the Oklahoma State. University.
2.
On leave from the Ll S. Army, 1965-67.
3.
T. Lehrfeld, a.,
4.
N.
5.
E. Kyburz, H. Els, St. Majnoni, G. Englert, C. van Planta, A. Fllrst, and Pl. A. Plattner, Helv. Chim. u, 49, 359 (1966). --
&,
1816 (1881).
H. Cromwell, R. P. Cahoy, W. E. Franklin, and G. D. Mercer, J. Amer. +. 922 (1957).
N. H. Cromwell, J. -Amer. Chem. a.,
2,
a.,
2,
4702 (1959).
H. W. Hay and B. P. Caughley, --Chem. Commun. (London), 58 (1965). A. B. Turner, H. W. Heine, J. Irving, and J. B. Bush, J. Amer. Chem. &.,
g,
1050 (1965).
E. Berterle, H. Boos, J. D. Dunitz, F. Elsinger, A. Eschenmoser, I. Felner. H. P. Gribi, H. Gschwend, E. F. Meyer, M. Pesaro, and R. Scheffold, w. --Chem. Intern. d. x., 2, 490 (1964). 10.
a.
0. E. Paris and P. E. Fanta, 2. -Amer. Chem. z., 74, 3007 (1952). J zer Chem Sot b. M. Prostenik, N. P. Salzman, and H. E. Carter, -*-*-*-**01* These are just a few of the many examples.
77
1856 (1954).
No.7,
ppa 873-876,
Pergamon
1968.
Press.
Printed
in
Great
Britain.
STEREOCHEMISTRY OF THE REACTION OF AMMONIA WITH DIETHYL BROMOFDMARATE AND DIETHYL BROt40MALRATE1 K. D. Berlin, Department of
Lenton G. Williams‘ and 0. C. Dermer Chemistry, Oklahoma State University Stillwater, Oklahoma
(Received
Very
few
esters
have
An old
report3
been
of
that
amount.s, n
diethyl the
as
were
1967)
cr-bromo-cu,p-unsaturated of
reactions
dibromosuccinate
reaction
aziridine
and none
with
stereochemistry
and diethyl
identified
in minor
The
reinvestigated
bromofumarate
products,
ammonia
recorded.
indicates
We have diethyl
reactions
in USA Q9 September
of
with
bromomaleate.
Each
II
III.
isolated.
carboxylic
such
been
esters
and ethanolic
ammonia
and enamine
of
and cu,t+dibromo
diethyl
of
the
ammonia
meso-
four
isomers
of
gave
II
were
CH3CH202C .
steric
more of
requirements
stable
enamine
an cY,A-dibromo
bromide.4’5 the
of
immediately
indicates
that
yields
II
because Cromwell4
the
-cis
the
III the -cis has
It
compound
with
ammonia
probable
reaction
and _threo
esters
cannot
II
enamine
of
give
and no -cis
w
formed .
aziridine
bromide or
m
ervthro
into
aziridine
is
1 shows
displacement
hydrogen
the
carbonyl
Scheme
mixture
molecular
III
transition
the
and
bromide
the
trans
The
ester
enamine,and
and no -cis and -trans
postulated
the
vinylic type
with
agreed
sequence
form
prevent
that
the
the -cis
/
\ NH2
m
by trans
formation give
intermediate
873
the
of
the
first
step
our
form
work.
since can
ervthro
The
the
react or
trans
form
can II
elimination an enol
formation
in
and the
the
reaction
to
a vinylic
composition
components by two
of
collapse
routes:
intra-
elimination produce
of
the trans
and
displacement
same products in
creation
in
aziridine
intramolecular
its
dehydrohalogenation
azfridine, the
only
apparently
C=C/COZCH2CH3
is
be determined
isomer
bromides
cis
and amines
of
The
of
the
Conversely
three
but
but
III
The three
yield
formation
aziridine.
this
III.
to
reacts
of
generally
enamine.
enamine. erythro
ion
state is
formed,
II
of
I.
same two
were
expected
‘H
CH3CH202E.’ the
aziridine
the
some amides
\ H-
yield
unknown.
and a-dibromosuccinate,
esters
Undoubtedly
--Cis/trans
has
acid
of of
bromide
hydrogen
intermediate in about of -cis
to
bromide
seems the
yield
necessary
same ratio.
and -trans
ethylen-
No.7
875
No.7
imine
Experimental
ketones.
from 1,4-addition
en01 resulting
in the intermediate our case
steric
reaction
species
IR analysis carbonyl
of III
ketone
a brosd
signal
state
the most favored indicates
typical
leading
to the -cis
hydrogen
A singlet
are observed.
ratios.
asiridine
of groups
Apparently causes
in
the
III.
bonding 7
of the
and interactions
to form trans
groups.
conformation
product
of such compounds.
ethyl
(amine protons)
sizes
cisftrans
intramolecular
due to non-equivalent
at 6 6.59
relative
conformation
strong
group and the amine protons,
CDC13 shows peaks
is a most favored
can explain
in the transition
to take
there
of an amine and that
crCbromo-S-amino
hindrance
suggests
evidence’
between an ester
The NMR spectrum
at 6 5.45
Ensmine III
(vinyl
resisted
of III
proton)
all
in and
acylation
attempts. Aziridine
The IR spectrum
analysis. of II 2.84
II was identified
showed peaks (ring
to steric
ethsnolic
could
readily
g-Dnsubstituted derivatives,
which 9
the eeiridines. gave only
diethyl
aziridines lose
fumerate.
indicating
that
dilute
reaction
proceeds
perchloric
to authentic
acid
with
inversion
and subsequent
DL-erythro-R-hydroxysspartic
that
similar
and 6
stereochemistry
II was trans
8
With II
to those
owing
and
reported.
yield
the &nitroso
of the same stereochemistry
and triethylamine
-60°
in ether
as
at -60’
structure. ‘t
F02C2H5
?=F H5C202C
to 25’
H
‘+I
acid
and is highly hydrolysis acid
indicate
compounds.
-N20
dilute
acid
alkenes
chloride
7,
The NMR spectrum
(amine proton)
at low temperatures
II has the trans
,*’ H5C202C with
to
-cis
under conditions
H2C202C H*. H *’ &
of asiridines
at 6 1.85
IR and lMR
a-1-substituted-2,3-dibenzylaziridines
to yield
nitrosyl
data,
amine).
The assumption
chloride
of II with
ether -60’ Many cleavages
nftrosyl
Treatment
(C2H5j3N
(sec.
to the corresponding
N20 stereospecifically
NOCl
II
This
with
since
occurred
analytical
was insufficient
one isomer.
not be justified
no reaction
behavior,
and singlets
alone
only
by sodilmr ethoxide
sodium ethoxide,
groups
evidence
we had obtained
requirements
of chemical
band et 3280 cm.-’
ethyl
Spectroscopic
since
are epimerized
showed a single
due to equivalent
protons).
of the asiridine
on the basis
to yield
vicinal
stereospecific.
amino alcohols lob
Treatment
gave a compound identicsl
hydrochloride.
are known.
10
of II iith in IR spectrum
No.7
876
II
1. HCLOh, 80'
amino ester
2. NaHC03
HC1,80° 10 hrs.
Thus II has the trans structure.
Steric requirements are probably
sufficient in the
transition state leading to the -cis isomer of II to prevent its formation.
Only the aziridines
and enamines corresponding to II and III were obtained by treatment of dimethyl and di-g-propyl bromofumarate and dimethyl bromomaleate with ammonia in the corresponding alcohol. II could be N-acylated
Aziridine
in good yield with carboxylic acid chlorides and triethylamine.
talline products were obtained with 2,4_dichlorophenylacetyl
Crys-
chloride and E-nitrobenzoyl
chloride. When II was heated at 125' for 1.5 hours, it was converted almost quantitatively to III, which evidently has the greater stabi!ity. References: 1.
We gratefully acknowledge partial support by the Research Foundation in the Oklahoma State. University.
2.
On leave from the Ll S. Army, 1965-67.
3.
T. Lehrfeld, a.,
4.
N.
5.
E. Kyburz, H. Els, St. Majnoni, G. Englert, C. van Planta, A. Fllrst, and Pl. A. Plattner, Helv. Chim. u, 49, 359 (1966). --
&,
1816 (1881).
H. Cromwell, R. P. Cahoy, W. E. Franklin, and G. D. Mercer, J. Amer. +. 922 (1957).
N. H. Cromwell, J. -Amer. Chem. a.,
2,
a.,
2,
4702 (1959).
H. W. Hay and B. P. Caughley, --Chem. Commun. (London), 58 (1965). A. B. Turner, H. W. Heine, J. Irving, and J. B. Bush, J. Amer. Chem. &.,
g,
1050 (1965).
E. Berterle, H. Boos, J. D. Dunitz, F. Elsinger, A. Eschenmoser, I. Felner. H. P. Gribi, H. Gschwend, E. F. Meyer, M. Pesaro, and R. Scheffold, w. --Chem. Intern. d. x., 2, 490 (1964). 10.
a.
0. E. Paris and P. E. Fanta, 2. -Amer. Chem. z., 74, 3007 (1952). J zer Chem Sot b. M. Prostenik, N. P. Salzman, and H. E. Carter, -*-*-*-**01* These are just a few of the many examples.
77
1856 (1954).