Note: Descriptions are shown in the official language in which they were submitted.
llZ18 13
The present invention relates to a process for
producing an optically active chrysanthemate wherein
2,5-dimethyl-2,4-hexadiene is reacted with a alkyl diazo-
acetate in the presence of a copper complex coordinated with
a novel kind of Schiff base.
Chrysanthemic acid is an important material for the
production of synthetic pyrethroids which are effective as
insecticides. There are four stereoisomers of chrysanthemic
acid: two kinds of geometric isomers, i.e. cis and trans,
each having d and 1 optical isomers. The pyrethroids derived
from d-trans and d-cis chrysanthemic acids are known to be
particularly effective in insecticidal activity. In this
connection, naturally occurring chrysanthemic acid is known
to have _-trans structure.
Two industrial methods are possible to prepare
optically active chrysanthemic acid. In one method, the
racemic mixture is synthesized first,and is subsequently
subjected to optical resolution. The other method is direct
asymmetric synthesis of the desired optical isomer.
One of the synthetic processes for preparing chrysan-
themic acid is to react an alkyl diazoacetate with
2,5-dimethyl-2,4-hexadiene in the presence of a copper
catalyst (see British Patent No. 74Q,014) and then to hydrolyze
the resulting alkyl chrysanthemate.
This invention is concerned with the asymmetric
synthesis of chrysanthemates. In our Belgian Patent
No. 787,473, a process is described and claimed for producing
an optically active alkyl chrysanthemate by reaction an alkyl
11;~1~113
diazoacetate with 2,5-dimethyl-2,4-hexadiene in the presence
of a copper catalyst coorainated with a chiral ligand according
to the following equation:
COOR
,5/ N2CHCOOR * ) *
Cu(L*) ~ ~ + ~ I ICOOR
n * ~ *
wherein L* is a chiral ligand.
We have found, as described in our Belgian Patent
~o. 810,959, that it is advantageous to catalyse the asymmetric
synthesis of alkyl chrysanthemates with copper complex
coordinated with chiral Schiff base having the following formula:
1 H R * R2
X ~ ~ C~ - C - OH
~ / R2 (I)
X2 ~ o~
wherein C* is an asymmetric carbon atom, Rl is selected from
the group consisting of (a) alkyl groups whose carbon atom
number is 1 - 10, and (b) aralkyl groups with or without alkoxy
substituent(s), whose total carbon atom number is 7 - 20, R2
is selected from aryl groups with alkoxy substituent(s), whose
total carbon atom number is 7 - 30, each of ~ and x2 is
selected from the group consisting of (a) hydrogen atom,
(b) alkyl groups having 1 - 10 carbon atoms, (c) phenyl group,
(d) alkoxy groups having l - 10 carbon atoms, (e) halogen atoms
and (f) nitro group, or (g) Xl and x2 together form a benzo
group.
In the following a further explanation will be given
or the novel Xind of chiral copper complexes used as catalysts
-- 2 --
11~1813
in our Belgian Patent No. 810,959.
When the Schiff base of the formula (Il forms a
metal complex with divalent copper ion, three kinds of
chelates are possible. (For the chemistry of metal complexes
of Schiff bases, see R.H. Holm, G.W. Everett, Jr., and
A. Chakravorty "Progress in Inorganic Chemistry" 7, 83-214,
(1966), Interscience Publishers, New York).
One has the following dimeric structure (II) wherein
the Schiff base behaves as tridentate ligand:
H Rl H R2 (II)
X C ~R2
wherein Rl, R2, Xl and X are as defined above. The other
has the following monomeric structure (III) or (IV) wherein
the Schiff base behaves as bidentate or tridentate ligand,
respectively,
x2 Hl R R
xl ~ - C*H - C - OH (III)
H R
,~ ~ \L o R ~IV)
wherein Rl, R2, Xl and x2 are as defined above, and L is a
neutral monodentate ligand. (for the copper complexes of
N-salicylidene-2-aminoethanol, see R.P. Houghton and
D.J. Pointer, J. Chem. Soc. 4214 (1965))
,~,'i ~
,~
1121813
We further made a study on the alkyl diazoacetate
used as the substrate in this asymmetric synthesis. As a
result, we found that the diazoacetate represented by the
general formula:
N2CHCOOR (V)
wherein R is selected from the group consisting of (a) mono-
or poly-cyclic cycloalkyl group with or without alkyl
substituent(s) whose total carbon atom number is 5 to 2Q,
(b) tertiary aralkyl group whose carbon atom number is 9 to 20,
and (c) tertiary alkyl group with or without alkoxy substitu-
ent(s~ whose total carbon atom number is 4 - 20, is particularly
effective for obtaining the resulting chrysanthemate with
excellent optical purity as well as high trans isomer content.
This fact is quite unexpected from reaction results using
primary diazoacetate of lower aliphatic alcohol having 1 - 8
carbon atom(s) such as ethyl ester.
The present invention has been accomplished on the
basis of this new knowledge. That is to say, the present
invention is a process for producing optically active chrysan-
themate characterized by the reaction of a alkyl diazoacetaterepresented by the general formula (V) with 2,5-dimethyl-2,4-
hexadiene in the catalytic use of a chiral copper complex
derived from the optically active Schiff base, for example
those having monomeric structure as shown by the general
formula (III~ or (IV), or those having dimeric structure as
shown by the general formula (II).
The invention comprises a process for the production
of an optically active alkyl chrysanthemate which comprises
the reaction of 2,5-dimethyl-2,4-hexadiene with a diazoacetate
of ..............................
~ .
8i3
the formula:
N2CHCOOR
wherein R is selected from the group consisting of (a) cyclo-
alkyl group with or without alkyl substituent(s) whose total
carbon atom number is 5 to 20, ~bl tertiary aralkyl group
whose carbon atom number is 9 to 20, and (c) tertiary alkyl
group with or without alkoxy substituent(s) whose total carbon
atom number is 4 to 20, in the presence of a copper complex
coordinated with a chiral Schiff base of the formula:
Xl H R R2
x2 ~ ~C*H - C - OH
wherein C* is an asymmetric carbon atom, Rl is selected from
the group consisting of (a) alkyl groups whose carbon atom
number is 1 to 10, and (b) aralkyl groups with or without
alkoxy substituent(s), whose total carbon atom number is 7 to
20, R is selected from aryl groups with alkoxy substituent(s),
whose total carbon atom number is 7 to 30, each of X and X is
selected from the group consisting of (a) hydrogen atom,
(b) alkyl groups having 1 to 10 carbon atoms, (c) phenyl group,
(d) alkoxy groups having 1 to 10 carbon atoms, (e) halogen atoms
and (f) nitro group, or (g) Xl and X together form a benzo
group.
The substituent group R of the diazoacetate
represented by the general formula (V) is previously mentioned,
but is exemplified by the following:
(a) The mono- or poly-cyclic cycloalkyl groups are
exemplified by cvclopentyl, 2-methylcyclopentyl, cyclohexyl,
2-methylcyclohexyl, 2,2-, 2,5- or 2,6-dimethylcyclohexyl,
-- 5
..~`.i.
11;Z1813
2,2,6-trimethylcyclohexyl, cyclo-octyl, cyclododecyl, etc.
Mono- or poly-cyclic cycloalkyl groups of naturally or non-
naturally occurring alicyclic alcohols are also effective.
For example, menthyl, isomenthyl, neomenthyl, neoisomenthyl,
carbomenthyl, bornyl, isobornyl, 2-norbornyl, 1- and 2-ada-
mantyl, etc. may be mentioned.
(b~ Tertiary aralkyl groups are exemplified by
a,a-dimethylbenzyl, triphenylmethyl, a,a-diphenylethyl,
2-phenyl-2-butyl, etc.
(c) Tertiary alkyl groups are exemplified by t-butyl,
t-amyl, 2,3-dimethyl-2-butyl, 2,3,4-trimethyl-3-pentyl,
al a-dimethyl-~-menthoxyethyl, etc.
The diazoacetates of the general formula (V) can have
either achiral or chiral structure. In the latter case, either
form of enantiomers or racemic modification can be used for
the present reaction. When chrysanthemate formed by the
present reaction shows some insecticidal power, it may be used
as insecticide by itself.
Although there is no limitation on the processes for
synthesizing the diazoacetate of the formula (V), the
following processes are examples:
(i) The method of diazotizing the corresponding ester of
glycine with nitrous acid or a nitrous acid ester. Refer for
example to Organic Syntheses, Coll. Vol.4, 424 and N. Takamura,
T. Mizoguchi, K. Koga and S. Yamada, Tetrahedron 31, 227 (1975~.
The ester of glycine can be synthesized by the reaction of
glycine with the corresponding alcohol or the corresponding
olefin.
. .
L..~,'~: ``;
li;~l813
(ii) The method of Regitz: P-toluenesulfonylazide is
reacted with the corresponding acetoacetate, and the resulting
2-diazoacetoacetate is deacetylated with a base to give
diazoacetate. Refer, for example, to Organic Syntheses,
Coll. Vol. 5, p. 179.
(iii) The method of House: Acid of the p-toluene-
sulfonylhydrazone of glyoxylic acid chloride is reacted with
the corresponding alcohol in the presence of a base. Refer,
for example, to Organic Syntheses, Coll. Vol. 5, p. 258.
The chiral Schiff base of the formula (I) is
synthesized by the reaction of a chiral amino alcohol having
the formula (VI) with a salicylaldehyde derivative having the
formula ~VII):
Rl _ C*H - C - OH (VI)
~H 2 R2
X H
~ (VII)
wherein Rl, R2, Xl and x2 are as defined above.
Specific examples of the substituent Rl in the
amino alcohol (VI) are methyl, ethyl, propyl, isopropyl,
butyl, isobutyl, 2-butyl, t-butyl, hexyl~ octyl, benzyl,
benzhydryl and 2,2-diphenylethyl. Among these examples,
preferred substituents or Rl are methyl, isopropyl, isobutyl,
benzyl, and a benzyl group having a substituent at the
4-position of the aromatic neucleus, of which the substituent
is, for example, methoxy, ethoxy, propoxy, isopropoxy,
~.~
1.813
butoxy, or hexyloxy, etc. As R in the amino alcohol,
a phenyl group having a substituent at the 2-position or
having substituents at the 2,5-positions is preferred.
Specific examples of 2-substituted phenyl groups are
2-methoxyphenyl, 2-ethoxyphenyl, 2-propoxyphenyl, 2-isopro-
poxyphenyl, 2-butoxyphenyl, 2-t-butoxyphenyl, 2-hexyloxyphenyl,
2-octyloxyphenyl, etc. Specific examples of 2,5-substituted
phenyl groups are 2-methoxy-5-methylphenyl, 2-butoxy-5-methyl-
phenyl, 5-methyl-2-octyloxyphenyl, 5-t-butyl-2-methoxyphenyl,
2-butoxy-5-t-butylphenyl, 5-t-butyl-2-octyloxyphenyl,
4-methoxybiphenyl-3-yl, 4-butoxybiphenyl-3-yl, 4-octyloxy-
biphenyl-3-yl, 2,5-dimethoxyphenyl, 2,5-butoxyphenyl,
2,5-dioctyloxyphenyl, etc.
The optically active amino alcohols of the formula
(:VI) to be used in this invention may be prepared in any of the
following two ways, one is by resolving a racemic mixture of
the corresponding amino alcohol with an appropriate resolving
agent, and the other by preparing the amino alcohol from the
reaction of optically active precursor. Thus, for example, an
optically active amino ester of the following formula (VIII)
with a Grignard reagent of the following formula (IX) gives
the optically active amino alcohol (:VI) with retention of
configuration.
R2
Rl _ C*H - coOR3 + R MgZ > R - IC*H - C - OH
H2 NH2 R
(VIII) (IX~ (VI)
~lZ11~13
wherein Rl is alkyl or aralkyl, R2 is aryl, R3 is alkyl of
1 - 10 carbon atoms or benzyl and z is chlorine, bromine or
iodine. As for the addition reaction of phenyl magnesium
bromide to (L)-alanine ethyl ester, see for example A. McKenzie,
R. Roger, GØ Willis, J. Chem. Soc., 779 (1926) and
B.M. Benjamin, H.J. Schaefer, C.J. Collins, J. Am. Chem.
Soc., 79 6160 (1957).
Specific examples of the salicylaldehyde derivatives
(VII) are salicylaldehyde, 3-ethoxysalicylaldehyde,
o-vanillin 3,5-dibromosalicylaldehyde, 5-chlorosalicylaldehyde,
3-nitrosalicylaldehyde, 3-isopropyl-6-methylsalicylaldehyde,
2-hydroxy-1-naphthaldehyde,l-hydroxy-2-naphthaldehyde and the
like.
Among the chiral copper complexes employed as
catalysts in the present invention, specific examples of the
copper complexes (II~, (III) and (IV) are those that are derived
from the following chiral Schiff bases:
(a) ~-salicylidene-2-amino-1,1-di(2-methoxyphenyl)-3-phenyl
-l-propanol.
(b) N-salicylidene-2-amino-1,1-di(2-isopropoxyphenyl)-3-phenyl
-l-propanol,
(c) N-salicylidene-2-amino-1,1-di(5-t-butyl-2-isopropoxyphenyl)
-3-phenyl-1-propanol,
(d) N-salicylidene-2-amino-1,1-di(2-butoxy-5-t-butylphenyl)
-3-phenyl-1-propanol,
(e) N-salicylidene-2-amino-1,1-di(5-t-butyl-2-heptyloxyphenyl)
-3-(phenyl)-1-propanol,
(f) N-salicylidene-2-amino-1,1-di(5-t-butyl-2-isopropoxyphenyl)
-l-propanol,
_ 9 _
11;~18 ~3
(g) ~-salicylidene-2-amino-1,1-di(2-butoxy-S-t-butylphenyl)
-l-propanol,
(h) N-salicylidene-2-amino-1,1-di(5-t-butyl-2-octyloxyphenyl)
-l-propanol,
(i) N-(3-methoxysalicylidene)-2-amino-1,1-di(5-t-butyl
-2-octyloxyphenyl)-1-propanol,
(j) ~-(3,5-dibromosalicylidene)-2-amino-1,1-di(2-isopropoxy-
phenyl)-3-phenyl-1-propanol,
(k) ~-(3ethoxysalicylidene)-2-amino-1,1-di(2-isopropoxyphenyl)
-3-phenyl-1-propanol,
(1) N-(2-hydroxy-1-naphthylmethylene)-2-amino-1,1-di(2-isopro-
poxyphenyl)-3-phenyl-1-propanol,
(m) ~-salicylidene-2-amino-1,1-di(4-butoxybiphenyl-3-yl)
-3-phenyl-1-propanol,
(n) N-salicylidene-2-amino-1,1-di(2,5-dibutoxyphenyl)-3-phenyl
-l-propanol,
(o) N-salicylidene-2-amino-1,1-di(2-butoxyphenyl)-3-methyl
-l-butanol, or
(p) N-salicylidene-2-amino-1,1-di(2-butoxy-5-t-butylphenyl)
-4-methyl-1-pentanol.
As copper complexes of the optically active Schiff
base of the formula (I), copper complexes of the previously
mentioned general formulae (II), (III) and (IV) are effective,
but the complex having dimeric structure of the formula (II)
is used particularly advantageously. The complex of the general
formula (II) is synthesized by the reaction of the Schiff base
of the general formula (I) with a cupric salt such as cupric
acetate.
-- 10 --
I ,,~j
.....
ll'~li~i3
The complex having monomeric structure of the
formula ~IV) is synthesized by the reaction of the dimeric
complex of the general formula (II) with a neutral monodentate
ligand, for example pyridine, picoline, lutidine, etc. The
cornplex having monomeric structure of the formula (III) is
synthesized by reacting a copper complex of the salicylaldehyde
derivative of the formula (VII) with the amino alcohol of the
formula (VI).
In the actual practice of the present invention, the
reaction can be carried out regardless of whether the chiral
copper catalyst is soluble or insoluble in the reacting system.
The catalyst may be recovered and purified for
repeated use by some appropriate method.
Preferably, the molar ratio of the copper complex to
alkyl diazoacetate (V) is in a range of 0.001 - 0.1.
Although t`he reaction temperature is not particularly
limited, usually a temperature between -50C. and 150C. is
suitable. In those cases where the reaction is carried out at
a temperature below the melting point of 2,5-dimetnyl-2,
4-hexadiene (15C.), a suitable solvent may be desirably added
to the reaction system. Aromatic hydrocarbons such as benzene,
toluene and xylene are suitable as the solvent in such cases.
The present invention is explained in further detail
by the examples set forth below. They are not, however, to be
taken as being limita-tive thereof.
In general, an unequivocal correlation exists between
the absolute configuration of the substance which induces
asymmetry and the absolute configuration of the substance to
which asymmetry is induced. Therefore, in this invention~ too~
-- 11 --
i3
it i5 needless to say that when the copper complex of
enantiomeric structure opposite to the one described in the
follow~ng examp~es is used as the catalyst, the resulting alkyl
chrysanthemate and the corresponding chrysanthemic acid will
also have the opposite enantiomeric structure.
Example 1
0.3 g. (0.2 m mol) of the dimeric copper complex of
(R)-~-salicylidene-2-amino-1,1-di(5-t-butyl-2-octyloxy)-pro-
panol (corresponding to the formula (II) wherein Rl = methyl,
R2 = 5-t-butyl-2-octyloxyphenyl, and Xl = x2 = hydrogen) was
dissolved in 17.6 g. (160 m mols) of 2,5-dimethyl-2,4-hexadiene.
To this solution was added dropwise a mixture of 4.4 g.
(40 m mols) of the above mentioned diene and 4.5 g. ~20 m mols)
of l-menthyl diazoacetate with stirring over a period of 7 hours.
At the beginning of the addition the solution of catalyst was
once heated to 75C. to initiate the decomposition of diazo-
acetate and thereafter the mixture was maintained at 40C. At
the end o~ the addition a nearly quantitative amount of nitrogen
gas was evolved.
The reaction mixture was distilled to recover the
unreacted excess diene (boiling point 45C./20 mm Hg) under
reduced pressure, and 4.7 g. of l-menthyl chrysanthemate was
obtained as an oil having a boiling point o~ 123C.jO.2 mm Hg.
The yield was 76% based on the diazo compound.
The l-menthyl ester was analyzed on gas chromatography
equipped with a glass capillary column (liquid phase QF-l) to
determine the composition of optical isomers of the
chrysanthemate.
- 12 -
llZ1~313
d-trans form 89.9 %; l-trans form 2.7 %;
total of d-cls and l-cis forms tseparation
was impossible) 7.4 %
It is calculated that the percentage of the trans
isomer in the ester is 93 ~,and the optical purity of the
trans isomers is 94 %.
A mixture of 4.2 g. of l-menthyl ester, 1.8 g. of
potassium hydroxide, 1.5 ml. of water and 11 ml. of ethanol
was heated at 100C. with stirring for 7.5 hours. After
distillation of ethanol from the reaction mixture, the residue
was diluted with water and was extracted with ether. The
alkaline aqueous solution was acidified with dilute sulfuric
acid, and was extracted with toluene. After the organic layer
was washed with water and dried, toluene was distilled off
under reduced pressure to give chrysanthemic acid (2.4 g.,
yield 90 %).
Chrysanthemic acid was reacted with d-2-octanol and
the resulting diasteromers were analyzed by gas chromatography
to determine the composition of optical isomers of chrysanthemic
acid.
_-trans form 90.4 %; _-trans form 4.7 %;
d-cis form 3.6 %; _-cls form 1.3 %
It is calculated that the optical purity of the trans isomers
is 90 % and that of the cis isomer is 47 %.
For the analysis of chrysanthemic acid, refer to
A. Murano, Agr. Biol. Chem., 36, 2203 ~1972)
Examples 2 - 6
Experiments similar to Example 1 were performed,
A - 13 -
11'~1~313
using dimeric chiral copper complexes shown in Table 1 and
l-menthyl diazoacetate. The results are summarized in Table 1.
The content of the trans isomer of l-menthyl chrysanthemate was
determined by gas chromatography. The optical purity of
chrysanthemic acid obtained after hydrolysis was determined by
gas chromatographic analysis of the corresponding (S)-1-methyl-1-
heptyl ester.
It should be noted that when a catalyst of (R)
configuration is used, dextrotatory-chrysanthemic acid is the
favoured product, and when a catalyst of (S)configuration is
used, laevorotatory-chrysanthemic acid is the favoured one.
Referential ExamPle 1
In place of chiral copper complex, copper powder was
used as catalyst in the reaction between l-menthyl diazoacetate
and 2~5-dimethyl-2,4-hexadiene. The results are shown in Table 1.
- 14 -
~'
1813
~ ~ ul I ~ o u~ C\J In o
.,, .~ .,., Ul ~o CU CU
.~ u
Q~ U
~n
. . . ,U ~ ~ ' O
a) co oo ~ o
o ~
l O
d ~ ~ r~
,,
.,,
a~~ . .
U ~ C~ ~ ~ o o o
a~
.,,
.1: ~ . N a)N Q~CU ~ C~
~ H . I ,C
t~ H C~l ~ $ O ~ o
X~: ~ o~ o
~ R ~ I R X R :~ R
~ ~ ~1~41 41 ~ 41 ~ 41 ~ ~
Q U u~ ou)~ Q u) S U) S 3
E~ O I ~ a
C~ :
o
q~ ~ ^ U~
~ ~ _ _ _ _ _ .
8 ~
,,
X ~ CU ~
~ ~ W
13
Examples 7 - 16
Experiments similar to Example 1 were performed,
using the diazoacetates shown in Table 2 and a chiral copper
complex (the formula (II) wherein the configuration is (R~ ,
R1 = methyl, R2 = 5-t-butyl-2-octyloxyphenyl and Xl = x2 =
hydrogen). The results are summarized in Table 2. The
content of trans isomer in the alkyl chrysanthemates was
determined by gas chromatography. The optical purity of
chrysanthemic acid obtained after hydrolysis of the esters
was determined by gas chromatographic analysis of corresponding
(Sl-l-methyl-1-heptyl ester.
The diazoacetates used in the examples were
synthesized either by the following ~A) method of (B~ method.
In (A) method, a corresponding glycine ester is
diazotized with isoamyl nitrite. The process is shown as
follows:
ROH ~ H2NcH2cooR > N2CHCOOR
As a typical example, the preparation of l-menthyl diazo-
acetate is shown in Example 17.
In (Bl method, the reaction proceeds as follows:
diketene ~ toluenesulfonylazide
ROH ~CH3 CCH2COOR -
corresponding
acetoacetate
alcohol
1l Na methoxide
CH3CCOOR ~ N2CHCOOR
~2 diazoacetate
~-diazoacetoacetate
- 16 -
~i
813
As a typical example, the preparation of 2,3,4-trimethyl
-3-pentyl diazoacetate is shown in Example 18.
Referential Example 2
In the use of the same copper catalyst as in
Examples 7 - 16, the reaction between ethyl diazoacetate
and 2,5-dimethyl-2,4-hexadiene was carried out.
The results are shown in Table 2.
ll;~l~i3
o .
to Ul U~ , ~ ~ , U~ ~ ~ , ,
a~ ,~ r~ I~ ~ U~
~ ~ U
.,, ~
.. ~
R~
~ ~ ~n
o ta ~ o t~ o In o ~ ~ ~ ~ ~ OD
~1 ~ ~ ~ CO 1` CO ~ 0 1
o U
U~ U~
00 ~ u~
~ ~o ~ ~ a) w co u~ I` I~ I` a~ n In
U~
a~
. ~ l ~ o ~ ~ ~ o
C~ ~
~rl _~ O u~ O ~ O O O O O O O
U ~ ~ ~ ~ d' ~ ~ d' ~O ~ d' ~ ~
td ~ o
.Y P~ ~
~ ~n
o o ~
tn ~ aJ
,, o ~ ~ m ma~
Q~
U~ Q~ ~
~ ~ ~ ~I
~ Id ~ ~1 -
U~ ~ .
. ~ R -
C\J N I ~ I ~ I
a ~
~D . ~ ~ 0
~} P~ ,r~ aX) ~
E~
. . C~ O O ~ O ~ ~'
u ~
CU
aJ
~1 a~ ~1
P~ ' S~
~ O t`CO ~ O ~ C~
X ~ X
P~
~ 8
11'~1813
Example 17
A mixture of l-men~hyl glycine (19.7 g.; 0.092 mol),
isoamyl nitrite (12.0 g.; 0.10 mol) and acetic acid (1.6 g.;
0.027 mol) in chloroform (400 ml) was heated with stirring for
25 minutes under reflux. The reaction mixture was washed with
l-N sulfuric acid followed by a saturated aqueous solution of
sodium bicarbonate and then water. After the organic phase was
dried, the xesidue (21 g.) obtained by condensation was purified
by column chromatography (silica gel 160 g., methylene chloride)
to give l-menthyl diazoacetate (15.0 g., 73%j.
Yellow crystal, [a]D - 86.8 (chloroform, c 1.0),
-IR (film) ~ 2125 cm
NMR (chloroform, TMS) ~ 5.29 ppm
For l-menthyl glycine, refer to K. Harada,
T. Hayakawa, Buil. Chem. Soc. Japan, 37, 191 (i964).
Example 18
To a mixture of 2,3,4-trimethyl-3-pentanol (24.3 g.;
0.18 mol) and triethylamine (0.1 g.) was added diketene (15.7 g ;
0.186 mol) dropwise at 70C. After the reaction mixture was
stirred at 110C. for 1.5 hours, it was distilled under reduced
pressure to give the corresponding acetoacetate (boiling point
84C./0.6 mm; 35.3 g.; 88 %).
To a mixture of the above mentioned ester (35.3 g.,
0.164 mol), triethylamine tl7 g., 0.168 mol) and acetonitrile
(200 ml) was added p-toluenesulfonylazide (38 g., 0.164 mol)
dropwise at room temperature. After the reaction mixture was
stirred for 1.5 hours, it was concentrated under reduced
pressure. The residue was extracted with ether (200 ml) and
- 19 -
the organic phase was washed twice with an aqueous solution
of potassium hydroxide (12.6 g.). The organic phase was dried
and concentrated to give the corresponding ~-diazoacetoaceta~e
O g.).
To a solution of the above ester (40 g.) in methanol
(65 ml) was added a sodium methoxide solution prepared from
sodium (4.2 g.) and methanol (65 ml) at 0C. After the
reaction mixture was further stirred for one hour at 0C.,
ice water (300 ml) was poured into it, sodium chloride was
added and the mixture was extracted with-ether (400 ml in total).
After the organic phase was washed with water and dried, it was
concentrated and distilled to give 2,3,4-trimethyl-3-pentyl
diaæoacetate (b.p. 59C./0.2 mm; 20 g.; 64%).
Yellow oil, IR (fiLm) J 2125 cm 1
NMR (chloroform, TMS) ~ 5.40 ppm
- 20 -
