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Deaminations of L-valine and L-valine benzyl ester
Tetrahedron Letters No.1, pp. 25-28,
1969. Pergamon Press.
Printed in Great Britain.
DEAMINATIONS OF L-VALINE AND L-VALINE BENZYL ESTER Shun-lchl Yamada, Haeao Tanlguchl and Kenjl Koga Faculty of Pharmaceutical.Sciences Unlvereltg of Tokyo, Bunkyo-ku, Tokyo, Japan (Received in Japan 15 November 1968;received in UK for publication 25 November 1968) There are extensive reports on the deamlnatlone of a-amino aclde and their esters, and the deaminatione of a-amino acids are generally recognized to occur with retention of configuration due to the participation of the neighboring carboxylate group, while the deaminatlons of a-amino acid eetere proceed with racemlzatlon together with an excess invereion about the a-carbon atom.1) Detailed examination of nitrous acid deamlnation of L-phenylalanlne ethyl ester in acetic acid, however, revealed that varloue rearranged and elimination products were obtained along with the corresponding a-acetoxy eater having 11% 8) net lnveralon of configuration. Since optically active a-amino acids are easily available, it ie of lntereet to examine the stereochemistry of the deamlnatlone of optically active a-amino acid esters.
Thle paper deals with an
extension of this reaction to the p-substituted allphatic amino acid ester, L-vallne benzyl eater.
The deamlnation of L-valine benzyl ester has been 9) briefly reported, but not in detail. To the solution of L-valine benzyl ester ( [a):+
12.1°(1.740, dloxane))
in acetic acid was addea 1.2 - 1.3 molar equivalents of sodium nitrite in portions for about 5 hours at 20 - 28°C.
After staneing overnight a mixture of
neutral reaction products was obtained by working up as usual.
GLC analyeia of
this reaction mixture gave 12 peaks a8 shown In the Chart ( 4.5 m. 3-5s caxbowax 2OM on Dlaeolid L at a column temperature of 176°C ). The structures of each peak were identified In the following manner. Compounds III, IV, VII, VIII, IX and X were Isolated from the reaction mixture and identified with authentic samples by means of IR and NMFi spectra as well ae
25
No.1
26
Compound III ( Cc4]:- 5.9"(5.310, benzene)) was proved to be 21%
(ILCtechnique.
net inversion of conl'lguratlonby leading it to methylethylacetlc acid of known d, upon catalytic hydrogenation. compound IX ( [a]:+ 6.6*(2.342, configuration benzene)) was aleo found to be 16% net lnverelon of configuration by comparleon with an authentic sample.
Although the Isolation of V, XI and XII wae un-
successful, the mixed portion of XI and XII wae shown to be a mixture of dlaetereoleomere of benzyl 2-methyl-3-acetoxybutyrate by comparleon with a eyntheeized dlaetereoleomerlc mixture of authentic eamples. v wae identified
CHART
I
Gaechromatogren CHa\
CHa’
CH-CH-COOCH,Ph-) I
pro&Wt8
time TABLE NO. I II
Structures
Product ratio(%)
No'
unidentified
Structure0
VII
CH,\ C=CH-COOCHpPh CHa'
VIII
CH~-~-CH~-COOCH8Ph
Product ratlot%
22
unidentified CHa
III
IV
CH,&H-CH-COOCHaPh I CHa ,CHa CH*=C 'CHs-COOCH8Ph
5-6
bH
l-2 IX 5-6
CHa, CH- H-COOCHaPh F CH/ OAc
2-3
"I". X V
CHa,
,COOCH,Ph o-1
/=C, CHa
VI
unidentified
XI XII
CHa-C-CHs-COOCHIPh dAC CHa-CH- H-COOCH,Ph F ACb CH.
55
6-7
to be bensyl angelate by comparleon with an authentic sample by means Of GLC technique.
The existence of benzyl tlglate, a Wane-Isomer
confirmed. The amount a of unknown compounde in three were too amall to be identified.
other
of V, could not be peakr,
I, II and VI,
The average ratio of the product8 la ehown in
the Table. Three conformatlone (a), (b) and (c) are euggeeted for
the etartlng amino
acid eater in the etereochemlstry of thle reaction.
PhCHpOOC
H
CHs
H
PhCHBOOC CHs
ml (a)
NH,
(b)
(0)
It ahould be noted that large amount8 of tertiary B-hydrogen ellmlnatlon and migration products, IV, VII, VIII and X, are obeerved.
Conelderlng the
concerted mechanlem with the loee of nitrogen, they muet be produced only from conformation (cl. However, (c) can not be expected to be populated to euch a large extent.
Then the open carbonlum Ion mechanism would participate In
forming IV, VII, VIII and X ; that le, the lnltlally formed (d) and (e) by way of dlazonlum Ion followed by the loea of nitrogen would rotate to give (f),
+ ACH.
PhCHaOOC
H H
CHe
(d)
PhCHpOOC H
CHa (e)
(f)
which undergoes hydrogen migration and ellmlnatlon. Ae previously mentioned, III and IX were obtained with 21% and 16% net lnvereion of configuration, respectively.
Thererore, the methyl migration and the eubetltutlon to iorm III
and IX can not be explained to occur either only by the open carbonlum ion mechanism ( with racemlzatlon ) or only by the concerted dlazonlum Ion mechanlru ( with complete Inversion ).
Moreover, V can not be formed by the latter
N0.l.
28
mechanism.
It, thus, aeems moat reasonable that both the open carbonlum ion
mechanism and the concerted dlazonlum Ion mechanlem will participate In the deemlnatlon
of
L-vallne benzyl ester.
Although the deamlnatlon of L-vallne has already been reported,995)
we
reinvestigated this reaction under condltlone similar to those described above. The product was led to benzyl eater with phenyldlazomethane and the unrearranged subetltutlon product IX ( [cf]i'- 39.7'(2.114, benzene)) was found to be almost only a product by GLC analysle, and moreover with at least 94% net retention of 6) conflguratlon. The deamlnatlon of 3-methyl-2-butylamine was reported to give a different pattern of products from that of the present L-vallne and L-vallne benzyl ester. Even though the carboxylate group ie coneldered to have a so-called "holding effect", there eeems a8 yet to be no clear explanation about the differences among the eater, carboxyl and methyl grollpe. We are now pursuing the clarlflcatlon of properties of carbonlum Ions adjacent to the carboxyllc acid derivatlvee. Acknowledgement
We are grateful to Mr. T. Nlzutanl (Kowa Company Ltd.)
for a help in operating the preparative GLC. References 1) P. Brewster, F. Hlron, E. D. Hughee, C. K. Ingold and P. A. D. S. Rao, Nature, 166, 179 (19501. 2) S. Yamada, T. Kltagawa and K.
Achlwa, Tetrahedron Letters, m,
3) G. Loese and 0. Bachmann, m.
&.,
x,
3007.
2671 (1964).
4) F. L. Welaenborn, J. W. Bolger, D. B. Rosen, L. T. Mann, Jr., L. Johnson and H. L. Holmes, 2. &I. m.
m.,
1792
,&
5) a) E. Fiecher and H. Schelbler, m. and A. Meleter, J. &.
u.
m.,
m., s,
(1954).
2,
2891 (1908). b) C. G. Baker
1336 (1951). c) M. Wlnltz, L. Bloch-
Frankenthal, N. Izumlya, S. M. Birnbaum, C. G. Baker and J. P. Greeneteln, 2. &.
m.
m.,
z,
2423 (1956).
d) Pl. A. Plattner, K. Vogler, R. 0.
Studer, P. Qultt and W. Keller-Schlerleln, m. 6) M. C.
Silver, L. &g.
m.,
28 _,
1686 (1963).
Chlm. Acta, 46, 927
(1963).
1969. Pergamon Press.
Printed in Great Britain.
DEAMINATIONS OF L-VALINE AND L-VALINE BENZYL ESTER Shun-lchl Yamada, Haeao Tanlguchl and Kenjl Koga Faculty of Pharmaceutical.Sciences Unlvereltg of Tokyo, Bunkyo-ku, Tokyo, Japan (Received in Japan 15 November 1968;received in UK for publication 25 November 1968) There are extensive reports on the deamlnatlone of a-amino aclde and their esters, and the deaminatione of a-amino acids are generally recognized to occur with retention of configuration due to the participation of the neighboring carboxylate group, while the deaminatlons of a-amino acid eetere proceed with racemlzatlon together with an excess invereion about the a-carbon atom.1) Detailed examination of nitrous acid deamlnation of L-phenylalanlne ethyl ester in acetic acid, however, revealed that varloue rearranged and elimination products were obtained along with the corresponding a-acetoxy eater having 11% 8) net lnveralon of configuration. Since optically active a-amino acids are easily available, it ie of lntereet to examine the stereochemistry of the deamlnatlone of optically active a-amino acid esters.
Thle paper deals with an
extension of this reaction to the p-substituted allphatic amino acid ester, L-vallne benzyl eater.
The deamlnation of L-valine benzyl ester has been 9) briefly reported, but not in detail. To the solution of L-valine benzyl ester ( [a):+
12.1°(1.740, dloxane))
in acetic acid was addea 1.2 - 1.3 molar equivalents of sodium nitrite in portions for about 5 hours at 20 - 28°C.
After staneing overnight a mixture of
neutral reaction products was obtained by working up as usual.
GLC analyeia of
this reaction mixture gave 12 peaks a8 shown In the Chart ( 4.5 m. 3-5s caxbowax 2OM on Dlaeolid L at a column temperature of 176°C ). The structures of each peak were identified In the following manner. Compounds III, IV, VII, VIII, IX and X were Isolated from the reaction mixture and identified with authentic samples by means of IR and NMFi spectra as well ae
25
No.1
26
Compound III ( Cc4]:- 5.9"(5.310, benzene)) was proved to be 21%
(ILCtechnique.
net inversion of conl'lguratlonby leading it to methylethylacetlc acid of known d, upon catalytic hydrogenation. compound IX ( [a]:+ 6.6*(2.342, configuration benzene)) was aleo found to be 16% net lnverelon of configuration by comparleon with an authentic sample.
Although the Isolation of V, XI and XII wae un-
successful, the mixed portion of XI and XII wae shown to be a mixture of dlaetereoleomere of benzyl 2-methyl-3-acetoxybutyrate by comparleon with a eyntheeized dlaetereoleomerlc mixture of authentic eamples. v wae identified
CHART
I
Gaechromatogren CHa\
CHa’
CH-CH-COOCH,Ph-) I
pro&Wt8
time TABLE NO. I II
Structures
Product ratio(%)
No'
unidentified
Structure0
VII
CH,\ C=CH-COOCHpPh CHa'
VIII
CH~-~-CH~-COOCH8Ph
Product ratlot%
22
unidentified CHa
III
IV
CH,&H-CH-COOCHaPh I CHa ,CHa CH*=C 'CHs-COOCH8Ph
5-6
bH
l-2 IX 5-6
CHa, CH- H-COOCHaPh F CH/ OAc
2-3
"I". X V
CHa,
,COOCH,Ph o-1
/=C, CHa
VI
unidentified
XI XII
CHa-C-CHs-COOCHIPh dAC CHa-CH- H-COOCH,Ph F ACb CH.
55
6-7
to be bensyl angelate by comparleon with an authentic sample by means Of GLC technique.
The existence of benzyl tlglate, a Wane-Isomer
confirmed. The amount a of unknown compounde in three were too amall to be identified.
other
of V, could not be peakr,
I, II and VI,
The average ratio of the product8 la ehown in
the Table. Three conformatlone (a), (b) and (c) are euggeeted for
the etartlng amino
acid eater in the etereochemlstry of thle reaction.
PhCHpOOC
H
CHs
H
PhCHBOOC CHs
ml (a)
NH,
(b)
(0)
It ahould be noted that large amount8 of tertiary B-hydrogen ellmlnatlon and migration products, IV, VII, VIII and X, are obeerved.
Conelderlng the
concerted mechanlem with the loee of nitrogen, they muet be produced only from conformation (cl. However, (c) can not be expected to be populated to euch a large extent.
Then the open carbonlum Ion mechanism would participate In
forming IV, VII, VIII and X ; that le, the lnltlally formed (d) and (e) by way of dlazonlum Ion followed by the loea of nitrogen would rotate to give (f),
+ ACH.
PhCHaOOC
H H
CHe
(d)
PhCHpOOC H
CHa (e)
(f)
which undergoes hydrogen migration and ellmlnatlon. Ae previously mentioned, III and IX were obtained with 21% and 16% net lnvereion of configuration, respectively.
Thererore, the methyl migration and the eubetltutlon to iorm III
and IX can not be explained to occur either only by the open carbonlum ion mechanism ( with racemlzatlon ) or only by the concerted dlazonlum Ion mechanlru ( with complete Inversion ).
Moreover, V can not be formed by the latter
N0.l.
28
mechanism.
It, thus, aeems moat reasonable that both the open carbonlum ion
mechanism and the concerted dlazonlum Ion mechanlem will participate In the deemlnatlon
of
L-vallne benzyl ester.
Although the deamlnatlon of L-vallne has already been reported,995)
we
reinvestigated this reaction under condltlone similar to those described above. The product was led to benzyl eater with phenyldlazomethane and the unrearranged subetltutlon product IX ( [cf]i'- 39.7'(2.114, benzene)) was found to be almost only a product by GLC analysle, and moreover with at least 94% net retention of 6) conflguratlon. The deamlnatlon of 3-methyl-2-butylamine was reported to give a different pattern of products from that of the present L-vallne and L-vallne benzyl ester. Even though the carboxylate group ie coneldered to have a so-called "holding effect", there eeems a8 yet to be no clear explanation about the differences among the eater, carboxyl and methyl grollpe. We are now pursuing the clarlflcatlon of properties of carbonlum Ions adjacent to the carboxyllc acid derivatlvee. Acknowledgement
We are grateful to Mr. T. Nlzutanl (Kowa Company Ltd.)
for a help in operating the preparative GLC. References 1) P. Brewster, F. Hlron, E. D. Hughee, C. K. Ingold and P. A. D. S. Rao, Nature, 166, 179 (19501. 2) S. Yamada, T. Kltagawa and K.
Achlwa, Tetrahedron Letters, m,
3) G. Loese and 0. Bachmann, m.
&.,
x,
3007.
2671 (1964).
4) F. L. Welaenborn, J. W. Bolger, D. B. Rosen, L. T. Mann, Jr., L. Johnson and H. L. Holmes, 2. &I. m.
m.,
1792
,&
5) a) E. Fiecher and H. Schelbler, m. and A. Meleter, J. &.
u.
m.,
m., s,
(1954).
2,
2891 (1908). b) C. G. Baker
1336 (1951). c) M. Wlnltz, L. Bloch-
Frankenthal, N. Izumlya, S. M. Birnbaum, C. G. Baker and J. P. Greeneteln, 2. &.
m.
m.,
z,
2423 (1956).
d) Pl. A. Plattner, K. Vogler, R. 0.
Studer, P. Qultt and W. Keller-Schlerleln, m. 6) M. C.
Silver, L. &g.
m.,
28 _,
1686 (1963).
Chlm. Acta, 46, 927
(1963).