Note: Descriptions are shown in the official language in which they were submitted.
~L45~
The present invention relates to certain new N,N-disubstitutea
ethylglycine (thiol)esters, to a process for their preparation and to their use
as fungicides.
It has already beeTI disclosed that such halogenoacetanilides as, for
example, N-chloroacetyl-N-(2,6-dialkylphenyl)-alanine alkyl esters and -glycine
alkyl esters can be employed with good success for combating fungal diseases of
plants (see DT-OS (German Published Specification) 2,350,944 and United States
Patent Specification 3,780,090). However, their action is not always completely
satisfactory, especially when small amounts and low concentrations are used,
and in particular also in combating Phytophthora species.
The present invention now provides, as new compounds, the N,N-disub-
stituted ethylglycine (thiol)esters of the general formula
R2 Rl f 2H5 1l
/ CH - C - Y - R
~ N /
R ~C - R
o
in which R represents alkyl, hydroxyalkyl, cyanoalkyl, alkenyl, alkynyl, halo-
genoalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, acyloxy-alkyl, alkylthioalkyl, alkylsulphinylalkyl, alkylsulphonylalkyl, dialkylamino-
alkyl or aralkyl optionally substituted by one or more substituents selected
from halogens, cyano, nitro, alkyl with 1 or 2 carbon atoms or halogenoalkyl
with 1 or 2 carbon atoms and up to three identical or different halogen atoms;
Rl represents hydrogen, alkyl, alkoxy or halogen; R2 represents hydrogen, alkyl,alkoxy or halogen; R represents hydrogen or alkyl; Y represents oxygen or
sulphur and R4 represents furyl, tetrahydrofuryl, thienyl or tetrahydrothienyl;
isoxazolyl which is optionally substituted by alkyl; hydroxyalkyl; alkyl,
- 1 -
B
~, ,
53~
alkenyl or alkynyl which is optionally subs~ituted by cyano or thiocyano;
cycloalkyl; dihalogenoalkyl; or the grouping -CH2-Az, -CH20R , -CH2-SR , -OP~ ,
-SR , -CH2-OSO2R , -CH20COR or -CH2-0 ~ wherein R represents an alkyl,
alkenyl, alkynyl, which alkyl, alkenyl or alkynyl group is optionally substi-
tuted by halogen, cyano or thiocyano, or an alkoxyalkyl group and Az represents
pyrazol-l-yl, 1,2,4-triazol-1-yl or imidazol-l-yl.
It has been found that the N,N-disubstituted ethyl-glycine (thiol)-
esters of the formula I have powerful fungicidal properties.
Those compounds of the formula I are preferred in which R represents
straight-chain or branched alkyl with 1 to 6 carbon atoms; hydroxyalkyl or
cyanoalkyl with in either case 1 to 4 carbon atoms in the alkyl part; alkenyl
or alkynyl with 2 to 4 carbon atoms; halogenoalkyl with 1 to 4 carbon atoms and
up to 5 halogen atoms ~especially with up to 2 carbon atoms and up to 3 identi-
cal or different halogen atoms, preferred halogens being fluorine and chlorine);
cycloalkyl with 3 to 7 carbon atoms, cycloalkylalkyl with 3 to 7 carbon atoms
in the cycloalkyl part and 1 to 4 carbon atoms in the alkyl part; alkoxyalkyl,
alkoxyalkoxyalkyl, alkylthioalkyl, alkylsulphinylalkyl 9 alkylsulphonylalkyl or
dialkylaminoalkyl with 1 to 4 carbon atoms in each alkyl part; acyloxyalkyl
with 1 to 4 carbon atoms in the alkyl part, ~he acyl part having the general
formula R7-Co- wherein R denotes alkyl with 1 to 4 carbon atoms, halogenoalkyl
with 1 to 4 carbon atoms and up to 5 halogen atoms (especially with up to 2
carbon atoms and up to 3 identical or different halogen atoms, preferred
halogens being fluorine or chlorine) or aryl with 6 to 10 carbon atoms or
aralkyl with 6 to 10 carbon atoms in the
'~3,l - 2 -
' ' ' ,. '
,
3 ~'~
aryl part and 1 to 4 carbon atoms in the alkyl part
(especially phenyl or benzyl), the aryl radical or the
aryl part of the aralkyl radical optionally carrying one or
more substituents selected from halogen(especially
: fluorine, chlorine andbromine), cyano, nitro, alkyl with 1
to 2 carbon atoms or halogenoalkyl with up to two carbon
atoms and up to 3 identical or different halogen atoms
(preferred halogens being fluorine or chlorine and tri-
fluoromethyl being mentioned as an example); or aralkyl
which has 6 to 10 carbon atoms in the aryl part (which is
preferably phenyl) and 1 to 4 carbon atoms in the alkyl
part, the aryl part optionally carrying one or more
substituents selected from halogen (especially fluorine,
chlorine and bromine), cyano, nitro, alkyl with 1 or 2
carbon atoms and halogenoalkyl with up to 2 carbon atoms
and up to 3 identical or different halogen atoms (pre-
ferred halogens being fluorine and chlorine, and tri-
fluoromethyl being mentioned as an example),
R1 and R2 are identical or different and each re-
present hydrogen, straight-chain or branched alkyl or
alkoxy with 1 to 4 carbon atoms or halogen (especially
~luorine, chlorine or bromine),
R3 represents hydrogen or straight-chain or branched
alkyl with 1 to 4 carbon atoms,
Y represents oxygen or sulphur,
R represents furyl~ tetrahydrofuryl, thienyl or
tetrahydrothienyl; isoxazolyl which is optionally sub-
stituted by methyl or ethyl; hydroxyalkyl with 1 to 2
carbon atoms; alkyl with 1 to 4 carbon atoms,optionally
substituted by cyano or thiocyano; alkenyl or alkynyl
with in either case 2 to 4 carbon atoms, optionally
substituted by cyano or thiocyano, cycloalkyl with 3 to 7
carbon atoms; dihalogenoalkyl with 1 to 2 carbon atoms
(preferred halogen atoms being fluorine and chlorine)~
or the grouping -CH2-Az, -CH2-oR5~ -CH2-SR5, -oR5,
Le A 19 573
-- 4 --
-SR5, -CH2-oSo2R5, -CH20CoR5 or -CH2-0 ~ 3
Az rep~esents pyrazol-l-yl, 1,2,4-triazol-1-yl o~
imidazol-l-yl, and
R5 represents alkyl with 1 to 4 carbon atoms or
alkenyl or alkynyl with in each case 2 to 4 carbon atoms,
in each case optionally substituted by halogen (especially
fluorine, chlorine or bromine), cyano or thiocyano, or
represents alkoxyalkyl with 1 to 4 carbon atoms in each
alkyl part.
The invention also provides a process for the
preparation of an N,N-disubstituted ethylglycine (thiol)-
ester of the formula (I) in which
(a) an N-phenyl-ethylglycine (thiol) ester of the
general formula
C~ H~ 0
R2 ~ ~ H - C - Y - R (II),
R3 H
in which
R, Rl, R2, R3 and Y have the meanings indicated
above,
is reacted with an acid chloride, bromide or anhydride of
the general formula
R4 - C - Cl(Br) (IIIa)
o
or
(R - C -)2 (IIIb),
in which
R4 has the meaning indicated above,
in the pre3ence of a diluent and if appropriate in the
presence of an acid-binding agent 3 or
(b) an N-acyl-N-phenyl-ethylglycine of the general formula
Le A 19 573
S3
-- 5 --
tzHso
R2 ~ R' ~CH- C - O - H
~ N (IV)~
R3 C -
o
in which
Rl, R2, R3 and R4 have the meanings indicated
above,
5 is reacted with an alcohol or thiol of the general formula
R - Y - H (V),
in which
R and Y have the meanings indicated above,
in the presence of a condensing agent and if appropriate
in the presence Or a diluent, or
(c) an N-acyl-N-phenyl-ethylglycine chloride of the
general formula
C2H~
R2~, CH- 9 Cl (VI),
R3 \ ~ ~ R~
in which
Rl' R2' R3 and R4 have the meanings indicated
above,
is reacted with an alcohol or thiol of the formula (V) in
the presence of a diluent and if appropriate in the presence
of a base, or
(d) an N-halogenoacetyl-N-phenyl-ethylglycine (thiol)ester
of the general formula
c2~
R2 ~ R~ ~ CH- ~ - Y - R (VII),
R3 ~ \ ~ - CH2 - Hal
Le A 19 573
s~
-- 6 --
in which
R, Rl, R2, R3 and Y have the meanings indicated
above and
Hal represents chlorine, bromine or iodine 3
is reacted with a compound of the general formula
B - X (VIII),
in which
X represents Az, cyano, thiocyano or the grouping
-oR5 or -SR5 or alkoxycarbonyloxy with 1 to 4 carbon
atoms in the alkyl moiety and
B represents hydrogen or an alkali metal,
in the presence of a diluent and if appropriate in the
presence of an acid-binding agent, or
(e) an N-hydroxyacetyl-N-phenyl-ethylglycine (thiol)-
ester, according to the invenkion, of the general formula
R~ ~ - CH2 - OH
in which
R, Rl, R2, R3 and Y have the meanings indicatec.
above,
(l) is reacted, if appropriate after activation by means
Of an alkali metal, with a halide of the general formula
Hal - R6 (X),
in which
Hal has the meaning indicated above and
R~ represents the radical R5 or the group -S02R5
or -COR ,
wherein
R5 has the meaning indicated above,
in the presence of a diluent and if appropriate in the
presence of an acid-binding agent, or
Le A 19 573
,
-- 7 ~
(2) is reacted with dihydropyrane, of the formula
~ (XI)~
in the presence of a diluent and if appropriate in the
presence of a catalyst.
Process variants (d) and (e) are applicable to the
preparation of only certain of the active compounds of the
formula (I).
Surprisingly, the N,N-disubstituted ethylglycine
(thiol)esters according to the invention display a con-
sidera~ly higher action, especially against Phytophthora,
than the N-chloroacetyl-N-(2,6-dialkylphenyl)-alanine
alkyl esters and -glycine alkyl esters which are known
from the state of the art and are closely related com-
pounds chemically and from the point of view of their
action. The active compounds according to the invention
thus represent an enrichment of the art.
The particularly preferred compounds of the formula (I)
are those in which R represents methyl, ethyl, n-propyl,
isopropyl, n-butyl, isobutyl, sec.-butyl, tert.-butyl,
hydroxyethyl, cyanomethyl, allyl, propargyl, chloroethyl,
cyclopropyl, cyclopropylmethyl, cyclohexyl, cyclohexylmethyl,
methoxyethyl, ethoxyethyl, methylthioethyl, ethylthioethyl,
methoxyethoxyethyl, chloroacetoxyethJl, methylsulphinylethy],
ethylsulphinylethyl, methylsulphonylethyl, ethylsulphonyl-
ethyl, benzyl which is optionally substituted by chlorineand/or by methyl andtor by ethyl, dimethylaminoethyl or
diethylaminoethyl; R3 represents hydrogen~ methyl, ethyl,
n-propyl, lsopropyl, n-butyl, isobutyl, sec.-butyl or
tert.-butyl, ~1 and R2 are identical or different and
3 represent hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-
butyl, isobutyl, sec.-butyl, tert.-butyl, methoxy, ethoxy,
isopropoxy, fluorine, chlorine or bromine, and R represents
Le A 19 573
~5~
- 8 -
2-furyl, 2-thienyl, 2-tetrahydrofuryl, 5-methylisoxazol-3-
yl, methoxymethyl, ethoxymethyl, allyloxymethyl, propargyl-
oxymethyl, ethoxymethoxymethyl, methylmercaptomethyl,
methoxy, ethoxy, methylmercapto, cyclohexyl, dichloro-
methyl, hydroxymethyl, methanesulphonyloxymethyl,acetoxymethyl, propionyloxymethyl, dichloromethyl, pyrazol-
l-yl-methyl, imidazol-l-yl-methyl, 1,2,4-triazol-1-yl-
methyl or tetrahydropyran-2-yl-oxymethyl.
The following compounds of the general formula (I)
may be mentioned specifically, in addition ~o the com-
pounds mentioned later in the preparative examples:
R; ~ l2R, O
R1 R2 R3 R~ Y R
.. . . , . . _ . . . .
H H H ~ ~ O -CH3
H H H ~1J -C2H5
H H H 0~ -CH2CH2Cl
H H H -~ O -CH2CH2OCH3
H H H ~0~ -CH2CH20C2H~OCH3
H H H ~0~ -CH2CH20COCH2Cl
H H H ~ O -CH2-CH=CH2
H H H ~rO~ -CH2-C- CH
H H H ~0
H H H - ~ O -CH
Le A 19 573
34;~
Rl R2 R3 R~ Y
,
H H H ~O~ -CH2cH2scH3
H H H ~ O~ O -CH2CH2SOCH3
H H H - ~ O -CH2CH2S02CH3
H H H ~O~ -CH2CHz~N(CH3 )2
H H H ~ O C
H H H rO~ -CH2CN
CH3 6-CH3 H ~ o -C2H3
CH3 6-CH3 H ~ O -CH2CHzCl
CH3 6-CH3 H -l~J -CH2cH2ocH3
CH3 6-CH3 H ~ O -cH2cH2oc2H4ocH~
CH3 6-CH3 H ~ ~ O -CH2CH20COCH~Cl
CH3 6-CH3 H ~O~ O -CH2-CH=CH2
CH3 6-CH3 H rO~ O CH2-C _ CH
CH3 6-CH3 H ~ O
CH3 6-CH3 H ~ O -CH2 ~
CH3 6-CH3 H ~ ~J O -CH2CH2SCH3
CH3 6-CH3 H ~oJ O -CH2CH2SOCH3
CH3 6-CH3 H ~ O -CH2CH2SO2CH~
Le A 19 573
~ '
` ~4S~4~
- 10 -
R R2 R3 R4 Y
CH, 6-CH3 H ~ O -C~H2C~H2 -N~C~H3 )a
CH3 6-CH3 H ~ O Cl
CH3 6-CH3 H ~ ~ J O -CH~ ClN
C~ 6-C2H5 H ~ -CH3
CH3 6-C2 Hs H ~O~ o -C2 Hs
CH3 6-C2Hs H ~ -CH2 CH2 Cl
CH; 6-C2 H5 H ~ O -CH2 CH2 OCH3
CH3 6-C2 H~ H ' ~ ~ O -CH2 CH2 OC2 H~OCH~
CH3 6-C2 Hs H ~O~ O - ~ 2 CH2 OCOCH2 Cl
CH3 6-C2 Hs H ~o J O -CH2 -CH-CH2
CH3 6-C2 Hs H ~ ~ O -CH2 -C - CH
CH3 6-C2H5 H ~ O
CH3 6-C2 Hs H ~ O~ O -CH2 ~
CH3 6-C2H~ H ~ O -CH2 CH2 S~H3
CH3 6-C2Hs H ~ O -CH2 CH2 SOCH3
CH3 6-C2Hs H ~ O -CH2 CH2 SO2 CH3
CH3 6-C2Hs H ~oJ O -CH2 CH2 -N(C'H~ )2
CH3 6-C2 Hs H ~ -CH2cl ~ Cl
CH~ 6-CzH~ H ~ O~ O -CHk CN
Le A 19 573
~ ~s3~2
R' R2 R3 F~4 y R
HHH-CH2-O-CH3 -CH3
HHH-CH2-O-CH3 -C2H9
HHH-CH2-O-CH3 O -CH2CH2Cl
HHH-CH2-O-CH3 O -CH2CH2OCH3
HHH-CH2-O-CH3 O -~zCHzOC2H40CH3
HHH-CH2~0-CH3 O -~2C~OCOC~Cl
HHH-CH2-O-CH3 O -CH2-CH=CH2
HHH-CH2-O-CH3 O -CH2-C_~
HHH-CH2-O-CH3 O
HHH-CH2-O-CH3 O -~2
HHH-CH2-O-CH3 O -~2~2S~
HHH-CH2-O-CH3 O -cH2cH2socH~
HHH-CH20-CH3 O -CH2CH2S~3
HHH-CH2-O-CH3 O ~2~2-N~
HHH-CH2-O-CH3 O Cl~Cl
HHH-CH2~0-CH~ O -~a~
LeA19573
-- 12 --
Rl R2 R3 R4 Y ~.
CH36-CH3 H -CH2-G-CH30 -CzH~
CH36-CH3 H -CH2-O~CH30 -CH2CH2Cl
CH36-CH3 H -CH20-CH30 -CH2CH20CH3
CH36-CH3 H -CH2-O-CH3 O -CH2 CH2 OC2 H4 OCH3
CH3 6-CH3 H -CH2-O-CH30 -CH2CH20cocH2
CH36-CH3 H -CH2-O-CH30 -CH2-CH=CH2
CH36-CH3 H -CH2-O-CH30 -~H2-C _ CH
CH3 6-CH3 H -CH2-O-CH30
CH3 6-CH3 H -CH2-O-CH30 -Cff2 ~
CH36-CH3 H -CH2-O-CH30 -CH2CH2SCH3
CH3 6-CH3 H -CH2 -O-CH30 -CH2CH2S9CH3
CH3 6-CH3 H -CH2 -O-CH3 O -CH2 CH2 SO2 CH3
CH36-CH3 H -CH2-O-CH30 -CH2 CH2 -N(CH~ )2
CH3 6-CH3 H -CH2-O-CH30 -CH~l ~ Cl
CH~ 6-CH~ H -CH2-O-CH30 -CH~CN
Le A 19 573
.
3~s~
Rl R R R Y R
CH3 6-C2H5 H -CH2-0-CH3 -CH3
CH3 6-C2H5 H -CH2-0-CH3 -C2H5
CH3 6-C2H5 H -CH2-0-CH3 o -CH2CH2Cl
CH3 6-C2H5 H -CH -O-CH O -CH2CH20CH3
CH3 6-C2H5 H-CH2-C~C~3 -CH2CH20C2H40CH3
Ch-3 6-C2H5 H -CH2-0-CH3 o 2 2 2
CH3 6-C2H5 H -CH2-0-CH3 0 2 2
CH3 6-C2H5 CH2-0-CH3 o 2
CH3 6-C2H5 H -CH2-0-CH3 0
CH3 6-C2H5 H -CH2-0-CH3 o -CH2 ~
CH3 6-C2H5 2 3 -CH2CH2SCH3
CH3 6-C2H5 2 3 -CH2CH2SCCH3
CH3 6-C2H5 H -CH2-0-CH3 o 2 2 2 3
CH3 6-C2H5 H -CH2-0-CH3 o -CH CH -N(CH )
CH3 6-C2H5 H -CH2-0-CH3 0 -CH2 ~ Cl
CH36--C2H5 HaCH2--0-CH3 0 --CH2CN
- 13 -
~53~L~
- 14 -
R' R2 ~3 R~ Y R
H H H -CH2-N ¦ -CH3
\N--
H H H -CH2 -~N -C2 H~
H H H -CH2 -~ ¦ O -CHz CH2 Cl
H H H -CH2 -N/~ O -CH2 CH2 OCH3
/=
H H H -CH2 -N -CH2 CH2 OC2 H~ OCH~
,/=
H H H -CH2 ~N\N -CH2 CH2 OCOCH2 Cl
H H H -5H2 ~NNJ -cH2-cH=cH2
~=
H H H -CH2 -N 0CH2 -C_ t:H
H H H -CH2-N~ O ~
~1 A
H H H -CH2 -\N ¦ -CH2 ~)
r=
H H H -CH2 -N~N O -CH2 CH2 SCH~
H H H -CHz -N -CH2 CH2 SOCH.I
H H H -CH2 -N~ O -CH2 CH2 SO2 ~H3
H H H -C~2 -N~/~ O -CH2 CHe -N ( CH3 )~
H H H -CH2 -1~ O -CH2 ;~Cl
H H H -CH2-NN~J ~ t:N
Le A 19 573
.
- 15 -
R' R2 R3 R~ Y R
CH3 6-CH3 H -CH2-N ~ -C2H3
CH3 6-CH3 H -CH2-~ ~ -CH2CH2Cl
CH3 6-CH3 H -CH2-N O -CH2CH2OCH3
~ ,
CH3 6-CH3 H -CH2-N -CH2CH20C2H~OCH~
CH3 6-CH3 H -CH2-N J o CH2 CH2 ococH2 Cl
CH3 6-CH3 H -CH2-N\N -CH2-CH=CH2
CH3 6-CH3 H -CH2-N~ ~ -CH2-C - CH
CH3 6-CH3 H -CH2-~ ~
CH3 6-CH3 H -CH2-N, ~ -CH
/=T
CH3 6-CH3 H -CH2-NN ~ -CH2CH2SCH
CH3 6-CH3 H -CH2-~ ~ -CH2CH2SOCH~
CH3 6-CH3 H -CH2-N~ ~ -CH2CH2SO2CH3
CH3 6-CH3 H -CH2-N~ ~ -CH2CH2-N(CH~)2
CH3 6-CH3 H -CH2-N\ ~ O -CH2 ~ Cl
CH3 6-CH3 H -CH2~N O -CH~CN
Le A 19 573
342
- 16 -
R1 R2 R3 R4 y R
CH3 6-C2H5 H -CHz -N~ ~ -CH3
CH3 6-C2 H5 H -CHz -~ ~ O -C2 Hs
CH3 6-C2 H5 H -CH2 -N ~ O -CH2 CH2 Cl
CH3 6-C2 H5 H -CH2 -N ~ -CH2 CH2 OCH3
CH3 6-Cz H5 H -CH2 -N J -CH2 CH2 OCz H4 OCH3
CH3 6-C2 H5 H -CH2 -N\ ~ -CH2 CH2 OCO OE ~ Cl
CH3 6-C2 H5 H -CH2 -N ¦ -CH2 -CH=CH2
CH3 6-C2 H5 H -CH2 -N ~ -CH2 -C - CH
CH3 6-C2 H5 H -CH2 - ~ O
CH3 6-C2H5 H -CH2 -N\ ~ -CH2 ~
CH3 6-C2 H5 H -CH2 -~ ~ -CH2 CHz SC~3
CH3 6-C2 Hs H -CH2 -~ ~ -CH2 CHzSOCH3
CH3 6-C2 H5 H -CH2 -N ~ O -CH2 CH2SO2 CH3
CH3 6-C2 H5 H -CHz -N~ ~ O -CH2 CH2 -N(CH~ )2
CH3 6-C2 H5 H -CH2 -N ~ -CH2~l ~ Cl
CH3 6-C2 H~ H -CH2 -N\ ~ O -CH~C3N
Le A 19 573
^ 17 -
Rl R2 R3 R4 y R
H H H -CHCl2 -CH3
H H H -CHCl2 O -Cz H5
H H H -CHCl2 O -CH2 CH2 OCH3
H H H -CHCl2 O -CH2-CH=CH2
H H H -CHCl2 O -CH2-C_ CH
H H H -CHCl2 O -CH2 CH2 OC2 Hs
H H H -CHCl2 O -C2 H4 OC2 H,, OCH3
H H H -CHCl2 O -CH2 CN
CH3 6-CH3 H -CHCl2 _C2 Hs
CH3 6-CH3 H -CHCl2 O -CH2 CH2 OCH3
CH3 6-CH3 H -CHCl2 0 -CH2-CH=CH2
CH3 6-CH3 H -CHCl2 O -CH2-C_ CH
CH3 6-CH3 H ~CHCl2 O -CH2 CH2 oC2 Hs
C~3 6-CH3 H -CHCl2 O -C2 H~ OC2 H~ OCH3
~CH3 6-CH3 H -CHCl2 O -CH2 CN
Le A 19 57~
s~
- ln-
R R R3 R4 Y R
Cl13 ~,-C2~15 1l -C~iClz -C~13
Cl~3 6-C2 H5 11 -Cl-ICl2 _C2 H5
Cl13 6-C211s H -CIICl2 O -CH2 CH2 OCH3
Cll~ 6-C2~ls H -CIICl2 O -CH -CH=CH2
Cl13 6-C2 H5 }~ -CHCl2 0 -CH2 -C--CH
C~i3 6-C2 H5 H -CHCl2 O -C2 H~ OCz Hs
CH3 6-C2 H5 H -CHCl2 0 -C2 H4 OC2 H" OCH3
CH3 6-C2H5 H -CHCl2 O -CH2 CN
H H H -CH2 OCOCH3 -CH3
H H H -CH2 OCOCH3 -C2 H5
H H H -CH2 OCOCH3 O -CH2 CH2 OCH3
H H H -CH2 OCOCH3 O -CH2 -CH-CH2
H H H -CH2 OCOCH3 O -CH2 -C--CH
H H H -CH2 OCOCH3 O -C2 H~,OC2 H~ OCH3
H H H -CH2 OCOCH3 O -CH2 CN
Le A 19 573
z
Rl R2 R3 R4 y R
. . ., ~
CH3 6-C2H5 H -CH2-OCOCH3 --CH3
CH3 6-C2H5 H -CH2-CCOCH3 -C2H5
CH36 C2H5 H -CH2-OCOCH3 0 -CH2CH20CH3
CH3 6-C2H5 H -CH2-OCOCH3 0 -CH2--CH-CH2
CH3 6-C2H5 H -CH2-OCOCH3 0 2 C
CH3 6-C2H5 H -CH2-OCOCH3 0 2 2 2 5
CH3 6-C2H5 H -CH2-OCOCH3 0 -C2H40C2H40CH3
CH3 6-C2H5 H -CH2-OCOCH3 0 2
CH3 6-CH3 H -CH2-OCOCH3 -C2H5
~H36-CH3 H -CH2-OCOCH3 0 -CH2CH20CH3
CH36-CH3 H -CH2-OCCCH3 0 -CH2-CH--CH2
CH36-C~I3 H -CH2-OCOCH3 0 2 C
CH36-C1~3 H -CH -OCOCH O 2 2 2 5
CH36-CH3 H ~ -CCOC 3 -C2H40C2H40CH3
CH36-CH3 H -CH2-OC~CH3 0 ~ CN
-- 19 --
-- 20 --
~=N
H H-CH2-N = O -CH~
/=N
H H H-CH2 -~ ¦ -C2 H~
H H H-CH2 -N~ O -C2 H~ OCH~
~=N
H H H-CH2-NN¦ O -CH2-CH=CH2
/=N
H H H-CH2-NN~ -CH2-C--CH
/~N
H H H-~H2 ~NN ~ -C2 H" OC2 H,
~N
H H H-CH2 -N I O -C2 H~ OC2 H~ OCH3
~N
H H H-CH2 N~N~ -CH2 CN
~N
CH3 6-CH~ H-CH2 -~N¦ -C2 H,
CH~ 6-CH!~ H-CH2 -N Cl -C2 ~ OCH
CH3 6~ H-cx2-r~ o -CH2-CH=CH2
~=N
CH~ 6 CH, H~CHa -~N¦ -CH2 -C~ CH
rN
CH3 6-CH3 2 ~N-~ -C2 H~, OC2 H~ -
rN
CH~ 6-CH~ H-CH2 -~~ -C;~ H4 OC2 H4 OC}I~
CH3 6~ N~ =~ O -~ CN
Le A 19 57~
.~ ~
-- 21 -
Rl R~R3 R~ Y R
f~N
CH36-C2 H5 H-CH2 -N J O -CH3
CH36-C2 H5 H-CH2 N JN -C2 H~
CH36-C2 H5 H-CH2-N ~ O -C2H~OCH3
/= N
CH36-C2 H5 H-CH2 -N ~ O -CH2-CH=cH2
CH35-C2 H5 H-CH2 -N ~ O -CH2 -C_ CH
/~N
CH36-C2 H5 H-CH2 -N ¦ O -C2H"OC2Hs
/=~N
CH36-C2H5 H-CH2-N ~ -C2 H~ C2 H4OCH3
~N
CH3 6-C2 H5 H-CH2-N~N~ o -CH2 CN
/=N
CH3 H H-CH2-N J -CH3
CH3 H H-CHCl2 -CH3
Cl 6 CH3 H~ 0~ -CH3
Cl 6-CH3 H~CH2OCH3 -CH3
Cl 6-CH3 H-C~I2-N~N¦ O -CH3
~ N
Cl 6-CH3 H-CHz-N ¦ Q -CH3
Cl 6-CH3 H-CHCl2 -C~I3
C(C~)3 H H~ J -CH3
C(C~)~ H H-CH2OCH3 -CH3
Le A 19 573
~L53~2
R' R2 R3 R~ Y R
C(CH3 )3 H H -CH2-N ~ -CH3
~N
C(CH3)3 H H -CH2-~N ¦ -CH3
C(CH3)3 H H -CHCl2 -CH3
CH3 4-CH3 6-CH3 ~ ~ ~CH3
CH3 4-CH3 6-CH3 -CH2OCH3 -CH3
CH3 4-CH3 6-CH3 -CH2-~ ~ -CH3
~=~N
CH3 4-CH3 6-CH3 -CH2-NN ¦ -CH3
CH3 4-CH3 6-CH3 -CHC12 -CH3
H H H ~ ~J S -CH3
H H H ~ ~ S ~C2Hg
H H H ~ S -CH2-CH=CH2
H H H ~ ~ S -CH2-C~CH
CH~ 6-CH3 H ~a s -CH3
CH3 6-CH3 H ~ S -C2Hs
CH3 6-CH3 H rO) S -CH2-CH=CH2
CH~ 6-CH~ H ~ ~J S -CH~ -C8 CH
Le A 19 573
3~2
- 23 --
R' R2 R' R~ Y R
CH3 6-C2Hs H ~ ~ S -CH3
CH, 6-C2H5 H ~ O S -C2Hs
CH3 6~C2Hs H ~0~ S -CH2-CH=CH2
CH3 6-C2Hs H ~ ~ S -CH2-C - CH
Cl 6-CH3 H ~ o3 S -CH3
Cl 6-CH3 H ~ S -C2Hs
Cl 6-CH3 H ~ 0~ S -CH2-CH=CH2
Cl 6-CH3 H ~ 0~ S -CH2-C _ CH2
CH3 H H ~~OJ S -CH3
CH3 H H -~J s -C2 H5
CH3 H H ~ ~ ~ S -CH2-CH=CH2
CH3 H H ~ ~ J S -CH2-C- CH
C(CH3)3 H H - ~J S ~CH3
C(CH3)3 H H rO~ S -C2Hs
C(CH3)3 H H ~0~ S -CH2 CH=CH2
C~CH,)3 H H ~oJ S -CH2-C-- CH
Le A 19 573
53~2
- 24 -
R' R2 R3 R~ Y R
~ . . ,
CH3 4-CH3 6-CH3 O S -CH3
CH3 4-CH3 6-CH3 O S -C2H5
CH3 4-CH3 6-CH3 S -CH2-CH=CH2
CH3 4-CH3 6-CH3 O S -CH2-C 5 CH
H H H -CH2OCH3 S -CH3
H H H -CH2OCH3 S -C2Hs
H H H -CH2OCH3 S -CH2-CH=CH2
H H H -CH20CH3 S -CH2-C_ CH
CH3 6-CH3 H -CH2OCH3 S -CH3
CH3 6-CH3 H -CH2OCH3 S -C2Hs
CH3 6-CH3 H CH2OCH3 S -CH2-CH=CH2
CH3 6-CH3 H -CH2OCH3 S -CH2-C_ CH
CH3 6-C2H3 H -CH2OCH3 S -CH3
CH3 6-C2H3 H -CH2OCH3 S -C2Hs
CH3 6~C2H5 H -CH2OCH3 S -CH2-CH=CH2
CH~ 6-C2H5 H -CH2OCH3 S -CH2-C - CH
Le A 19 573
~5~2
- 25 -
R' R2 R3 R~ Y R
Cl 6-CH3 H -CH2 OCH3 S -CH3
Cl 6-CH3 H -CH2 OCH3 S -Cz Hs
Cl 6-CH3 H -CH2 OCH3 S -CH2 -CH=CH2
Cl 6-CH3 H CH2 OCH3 S -CH2-C----CH
CH3 H H -CH2 OCH3 S -CH3
CH3 H H -CH2 OCH3 S -C2 H5
CH3 H H -CH2 OCH3 S -CH2 -CH=CH2
CH3 H H -CH2 OCH3 S -CH2 -C_ CH
C(CH3 )3 H H -CH20CH3 S -CH3
C(CH3 )3 H H -CH20CH3 S -C2H5
C(CH3 )3 H H -CH2 OCH3 S -CH2 -CH=CH2
C(CH3 )3 H H -CH20CH3 S -CH2 -C----CH
CH34-CH3 6-CH3-CHz OCH3 S -CH3
CH34-CH3 6-CH3-CH2 OCH3 S -C2 Hs
CH34-CH3 6-CH3-CHz OCH3 S -CH2 -CH-CH2
CH~ 4-CH3 6-CH3 -CH2OCH.: S -CH2 -C--CH
Le A 19 573
534
- 26 -
R' R2 . _ R~ Y R
H H H -CH2-N\ J S -CH3
N
H H H -CH2 -N~N~ S -Cz Hs
H H H -CH2-N~ S -CHz~CH=CH2
H H H -CH2-N\~ S -CH2-C----CH
CH3 6-CH3 H -CH2-N\~ S -CH3
CH3 6-CH3 H -CH2 -N~ S -Cz Hs
CH3 6-CH3 H -CH2-N\~ S -CH2-CH=CHz
CH3 6-CH3 H -CH2 -N\~ S -CH2 -C--CH
Cl 6-CH3 H -CH2-N,/~ S -CH3
N
Cl 6-CH~; H -CH2 -N\ J s -c2 H5
Cl 6-CH3 H -CH2-N ¦ S -CH2-CH=CH2
Cl 6-CH3 H -CH2 ~~ S -CH2-C_ CH
'N
CH3 H H -CH2-N\~ S -CH3
CH3 H H -CH2 -N\~ S -C2 Hs
CH3 H H -CH2-N J s -cH2-cH=cH2
CH2 H H -CH2-N\ ¦ S -CH2-C--CH
Le A 19 573
- 27 -
~ RZ R3 R4 y R
C(CH3)3 H H -CH2-N ¦ S -CH3
C(CH3)3 H H -CH2-N ~ S ~C2Hs
C(CH3)3 H H -CH2-N ~ S -CHz-CH=CH2
N
C(CH3)3 H H -CHz-N\ ~ S -CH2-C- CH
CH3 4-CH3 6-CH3 -CH2-N ~ S -CH3
CH3 4-CH3 6-CH3 -CH2-N ~ S -C2H5
CH3 4-CH3 6-CH3 -CH2-N\ ~ S -CH2-CH=CH2
~H3 4-CH3 6-CH3 -CH2-~ ~ S -CH2-C-- CH
If, for example, N-(2,6-xylyl)~ethylglycine methyl
ester and methoxyacetyl chloride are used as starting
materials in process variant (a), the course of the reaction
can be represented by the following equation:
C2H5
CH3 I Q
CH-C-OCH3 Cl-CG~CH~ ~CU3
H -HCl
CH3
CH3 CH - 3-oCH3
CH3 IC~-CH20CH3
Le A 19 573
3~
- 28 -
If, for examplé, N-dichloroacetyl-N-(2,6-xylyl)-
ethylglycine and propargyl alcohol are used as starting
materials and DCC is used as the condensing agent in
process variant (b), the course of the reaction can be
represented by the following equation:
C2H5 0
~CH3 / CH - C-OH +DCC*
N\ + HO-CH2-C- CH -DCH*
CH C - CHCl2
O C2H5
CH3 CH ~ C-O-CH2-C- CH
CH, ~ ~
*DCC = Dicyclohexylcarbodiimide
*DCU = Dicyclohexylurea
If, for example, N-(2-furoyl)-N-(2,6-xylyl)-ethyl-
glycine choride and O-methylglycol are used as starting
materials in process variant (c), the course of the reaction
can be represented by the following equation:
ÇzH5
CH3 ~H - ~-Cl Ho_cH2CH2-OCH3
\ ~ ~ ~ ~
CH3 CH - ~_o-cH2cH2ocH3
~ ' c l~J
If, for example, N-chloroacetyl-N-(2,6-xylyl)-ethyl-
glycine methyl ester and imidazole are used as starting
materials in process variant (d), the course of the reaction
can be represented by the following equation:
C2H,
~ CH ~ C-CHz-
~
Le A 19 573
5~
CH - g-OCH
CH3 IC~-CHz-N~
If, for example, N-hydroxyacetyl-N-(2,6-xylyl)-ethyl-
glycine methyl ester and ethoxymethyl chloride are used
as starting ~aterials in process variant (e)(1), the course
o~` the reactiorl can be represented by the followin~ equation:
CH ICz~ O ~ ase
CH3 C-CH2-OH + Cl-CH2-O-C2H~ -PCl
CzH~ 8
N\
CH ICI_CH2-O-CH2-O-C2H5
If, for example, N-hydroxyacetyl~N-(2,6-xylyl)-ethyl-
glycine methyl ester and 3,4-dihydro-4H-pyrane are used as
starting materials in process variant (e)(23, the course of
the reaction can be represented by the following equation:
C2H~
,CH3 CH ~ C-OCH~ O
CH~ C-CH2-OH
~H - C-OC
CH~ ~-CH2_
Le A 19 573
, . . .
z
The formula ~II) provides a general definition of the
N-phenyl-ethylglycine ~thiol)esters required a3 ~tar~ing
materials in carrying out process variant (a). In this
formula, R, Rl, R , R3 and Y preferably have those meanings
which have already been mentioned as preferred in connection
with the description of the compounds of the formula (I).
Some of the N-phenyl-ethylglycine (thiol)esters of
the formula (II) have been described in the literature (see
U.S. Patent Specification 4,096,167 and DE-OS (German Puh-
lished Specification) 2,805,525). They can be obtained
by reacting corresponding anilines with corresponding a-
halogeno-butyric acid (thiol)esters in the presence of an
acid-binding agent~ for example potassium carbonate, and in
the presence of an inert organic solvent, for example
dimethylformamide, and if appropriate in the presence of a
catalyst, for example potassium iodide, at temperatures
between 20 and 100C.
The N-phenyl-ethylglycine (thiol) esters of the
formula (II) can also be obtained when N-phenyl-ethyl-
glycines are esterified with corresponding alcohols orthiols by known processes, for example in the presence of
boron trifluoride (in this context, see also the statements
for process variant (b)).
Examples of the starting materials of the formula (II)
which may be mentioned are:
H~ 0
~; ~ ~ CH - C - Y - R (II)
R~ R2 R3 y R
H H H O(S) -CH3
H H H O(S) -C2H5
H H H O(S) -CH2CH2-0-CH3
H H H O(S) -CH2-CH=CH2
H H H O(S) -CH2-C -- CH
Le A 19 573
~53~2
31 -
..... Rl.' ',' ', .' '.''.. ' ',' '.R2.''.. '','' ' ' '' .~,3 '' '' ' 'Y ' '' ' ' ' 'R '' '' '' '' '' ' ' '' '' ''
.. .. .. . . ~
H H H O(S) -CH2 CH2 -O-C2H5
H H H O ~ S ) -C2 H~-O-C2H~ -OCH3
CH3 6-CH3 H O(S) -CH3
CH3 6-CH3 H O(S) -C2Hs
CH3 6-CH3 H O(S) -CH2 CH2 -O-CH3
CH3 6-CH3 H O(S) -CH2-CH=CH2
CH3 6-CH3 H O(S) -CH2-C - CH
CH3 6-CH3 H O(S) -cH2cH2-o-c2Hs
CH3 6-CH3 H O(S) -C2H~-O-CzH4-OCH3
C2H5 6-c2H5 H O(S) -CH3
C2H5 6-c2H5 H O(S) -C2H5
C2H5 6-C2H5 H O(S) -CH2CH2 O-CH3
C~H5 6-C2H5 H O(S) -CH2-CH=CH2
C2H~ 6-CzH5 H O(S) -CH2-C - CH
~2H5 6 C2HS H O(S) -cH2cH2-o-c2Hs
C2H5 ~-C2H5 H O(S) -C2H~-O-C2H4-OCH3
C2H5 6-CH3 H O(S) -CH3
C2H5 6-CH3 H O(S) -C2Hs
C2H~ 6-CH3 H O(S) -CH2CH2-O-CH
C2Hs 6-CH3 H O(S) -cH2~cH=GH2
C2H~ 6-CH3 H O(S) -CH2-C - CH
C2Hs 6-CH3 H O(S) -cHzcH2-o-c2Hs
C2 H5 6-CH3 H O(S) -C2H4-O-C2 H4 -OCH3
C(CH3)3 H H O(S) -CH3
C(CH3)3 H H O(S) -C2H5
C(CH3 )3 H H O(S) -CH2 CH2 -O-CH3
C(CH3 )3 H H O(S) -cH2-cH=cH2
C(CH3 )3 H H O(S) -CH2-C----CH
C(CH3 )3 H H O(S) -CH2CH2-O-C2H~
Le A 19 573
4S~
~ 32 -
... R .... :.R ....... R~ Y R
C(CH3 )3 H H O(S) -C2H"-O-C2H4-OCH3
CH3 3-CH3 H O(S) -CH3
CH3 3-CH3 H O(S) ~C2Hs
CH3 3-CH3 H O ( S ) -CH2 CH2 -O-CH3
CH3 3-CH3 H O ( S ) -cH2 -CH=C~I2
CH3 3-CH3 H O ( S ) -CH2 -C CH
CH3 3-CH3 H O ( S ) -CH2 CH2 -O-C2 H~
CH3 ~-CH3 H O ( S ) -C2 H" -O-C2 H" -OCH3
C2H5 H H O(S) -CH3
C2H~ H H O(S) -C2H5
Cz H5 H H O ( S ) -CH2 CH2 -O-CH3
C2 H~ H H O ( S ) -CH2 -CH=CH2
C2Hs H H O(S) -CH2-C_ CH
C2 Hs H H O ( S ~ -CH2 CH2 -O-C2 H~ -
C2H~ H H O(S~ -C2H~ O-C2H"-OCH3
i-C~ H7 H H O ( S ) -CH3
i-C3H7 H H O(S) -C2H~
i-C3H7 H H O(S) ~ CH7CH2-0-CH3
i -C3 H7 H H O ( S ) -CH2 -CH=CH2
i-C~s H7 H H O ( S 3 -CH2 -C--CH
i -C3 H7 H H O ( S ) -CH2 CH2 --C2 H3
i-C3 H7 H H O ( S ) -C2 H4 -O-C2 H" -9CH;
CH3 5-CH3 H O ( S ) -CH3
CH3 5-CH3 H O(S) -C2H,
CH3 5-CH3 H O ( S ) -CH2 CH2 -O-CH~
CH3 5-CH3 H O ( S ) -CH2 -CH=CH2
CH3 5-CH3 H O(S) -CH2~C CH
CH3 5-CH3 H O ( S ) -CH2 CH2 -O-C2 H~
CH3 5-CH3 H O ( S ) -C2 H~ ~O~C~ H~ -OCH,
Le A 19 573
~534
- 33 -
R2, .;R3 y .R : :
: ,..... . . .
Cl 6-CH3 H O(S) -CH3
Cl 6-CH3 H O(S) -C2H~
Cl 6-CH3 H O(S) -CH2CH~-O-CH3
Cl 6-CH3 H O(S) -CH2-CH=CH2
Cl 6-CH3 H O(S) -CH2-C_ CH
Cl 6-CH3 H O(S) CH2CH2-O-C~H~
Cl 6-CH3 H O(S) -C2H4-O-C~H~-OCH~
Cl 6-C(CH3)3 H O(S) -~H,
Cl 6-C(CH3)3 H O(S) -C2H~
Cl 6-C(CH3)3 H O(S) -CH2CH2-0-CH3
Cl 6-C(CH3)3 H O(S) -CH2-CH=CH2
Cl 6-C(CH3)3 H O(S) -CH2-C- CH
Cl 6-C(CH3)3 H O(S) -CH2CH2-O-C2H5
Cl 6-C(CH3)3 H O(S) -C2H~-O-C2H~-OCH~
CH3 ~-CH3 6-CH3 O(S) -CH3
CH3 3-CH3 6-CH3 0(S) -C2H~
CH3 3-CH3 6-CH3 O(S) -CH2CH2-O-CH3
CH3 3-CH3 6-CH3 O(S) CH2-CH-CHz
CH3 3-CH3 6-CH3 O(S) -CH2-C - CH
CH3 3-CH3 6-CH3 O(S) -CH2CH2-O-C2H~
CH3 3-CH3 6-CH3 O(S) -c2H~-o-c2H~-o~H3
CH3 ~-CH3 6-CH3 O(S) -CH3
CH3 4-CH3 6-CH3 O(S) -CzH3
CH3 4-CH3 6-CH3 O(S) -CH2CH2-O CH~
CH3 4-CH3 6-CH3 O(S) -CH2-CH=CH2
CH3 4-CH3 6-CH3 O(S) -CH2-C_ CH
CH3 4-CH3 6-CH3 O(S) -CH2CH2-O-C2H~
CH3 4-CH3 6-CH~ O(S) -C~H~-O-C2H4-OSH~
Le A 19 573
- 34 -
Rl R2 R3 Y R
i-C3 H76-i-Ç3 H7 H O(S) -CH3
i-C3 H76-i-C3 H7 H O(S) -C2 H,
i-C3 H76-i-C3 H7 H O(S) CH2 CH2 -O-CH3 -
i-C3 H76-i-C3 H7 H O(S) -CH2 -CH-CH2
i-C3 ff76-i-C3 H7 H O(S) -CH2 -C - CH
i-C3 H76-i-C3 H7 H O(S) -CH2 CH2 -O-C2H
i-C3 H76-i -C3 H7 H O(S) -C2 H~ -O-C2 H~ OC~I~
OCH3 6-CH3 H O(S) -CH3
OCH3 6-CH3 H O(S) -C2 H~
OCH3 6-CH3 H O(S) -CH2 CH2 -O-CH3
OCH3 6 CH3 H O(S) -CHz -CH=CH2
OCH3 6-CH3 H O(S) -CH2 -C C~H
OCH3 6-CH3 H O(S) -CH2 CH2 -O-C2 H3
OCH3 6-CH3 H O(S) -C2 H~ -O-C2 H~ -OC~I~
Br 6-CH3 H O(S) -CH3
Br 6-CH3 H O(S) ~C2H~
Br 6-CH3 H O~S) -CH2 CH~ -O-C~
Br 6-CH3 H O(S) -CH2 -CH=CH2
Br 6-CH3 H O(S) -CH2 -C _ C~H
Br 6-CH3 H O(S) -CH2C~H~ --~2 ~b
Br 6-CH3 H O(S) ~Ca H4 -O-c~ CX~H~
Le A 19 573
- 35 -
R' R2 R3 Y
OCH3 6-OCH3 H O ( S ) -CH3
OCH3 6-oCH3 H 0(~;) -C2HS
OCH3 6-oCH3 H O t S ) -C~12 CH2 -O-CH3
OCH3 6-oCH3 H O ( S ) -cH2 -CH=CH2
OCH3 6-oCH3 H O(S) -CH2 -C_ CH
OCH3 6-OCH3 H O ( S ) -CH2 CH2 --C2 H5
UCH3 S-OCH3 H O(S) -C2H~-O-CzH~-OCH3
The formulae (IIIa) and (IIIb) provide general
definitions of the acid chlorides, bromides and anhydrides
also to be used as starting materials for process variant
(a). In these formulae, R4 preferably has those meanings
which have already been mentioned as preferred in connection
with the description of the compounds of the formula (I).
The acid chlorides, bromides and anhydrides of the
formulae (IIIa) and (IIIb) are generally known compounds
of organic chemistry.
The formula (IY) provides a general definition of the
N-acyl-N-phenyl~ethylglycines to be used as starting
20 materials for process variant (b). In this formula, Rl,
R2, R3 and R4 preferably have those meanings which have
already been mentioned as preferred in connection with the
description of the compounds of the formula (I).
The N-acyl-N-phenyl-ethylglycines of the formula (IV)
25 have not hitherto been described in the literature. However,
they can be obtained in a simple manner by reacting N-phenyl-
ethylglycines with acid chlorides of the formula (IIIa) in
the presence of an acid-binding agent 3 for example sodium
hydroxide solution, and in the presence of an inert organic
solvent, ~or example methylene chloride, at temperatures
between 0 and 120C.
Le A 19 573
53
- 36 -
The formula (V) provides a géneral definition of
the alcohols and thiols also ~o be used as starting materials
for process variants ~b) and (c). In this formula,
R and Y preferably have those meanings ~Jhich have already -
been mentioned as preferred in connection with the des-
cription of the compounds of the formula (I).
The alcohols and thiols of the formula (V) are
generally known compounds of organic chemistry.
The formula (VI) provides a general definition of
10 the N-acyl-N-phenyl-ethylglycine chlorides to be used as
starting materlals for process variant (c). In this
formula, Rl, R2, R3 and R4 preferably have those meanings
which have already been mentioned as preferred in con-
nection with the description of the compounds of the
15 formula (I).
The N-acyl-N phenyl-ethylglycine chlorides of the
formula (VI) have not hitherto been described in the
literature. However, they can be obtained in a simple
manner by reacting the N-acyl-N-phenyl-ethylglycines of
20 the formula (IV) with, preferably, oxalyl chloride in the
presence of dimethylformamide or pyridine.
The formula (VII) provides a general definition of
the N-chloroacetyl-N-phenyl-ethylglycine (thiol)esters
required as starting materials in carrying out process
25 variant (d). In this formulag R, Rl, R2 and R3 preferably
have those meanings which have already been mentioned as
preferred in connection with the description of the com-
pounds of the formula (I).
Some of the N-chloroacetyl-N-phenyl-ethylglycine
30 (thiol)esters of the formula (VII) have been described
in the literature (see U.S. Patent Specification 4,096,167
and DE-OS (German Published Specification) 2,805,525).
They can be obtained, for example, by reacting N-phenyl-
ethylglycine (thiol)esters o~ the formula (II) with
~5 chloroacetic acid chlorides analogously to process variant
(a).
Le A 19 573
- 37 ~
The formula (VIII) provides a general défini~ion
of the compounds also to be used as rurther starting
substances for process variant (d). In this formula, Az
and R5 preferably have those meanings which have already
been mentioned as preferred in connection with the des-
cription of the compounds of the formula (I). B pre-
ferably represents hydrogen, sodium or potassium.
The compounds of the rormula ~VIII) are generally
known compounds of organic chemistry.
The formula (IX) provides a general definition of
the N-hydroxyacetyl-N-phenyl-ethylglycine (thiol)esters
required as starting materials in carrying out process
variant (e). In this formula, R, Rl, R2 and R3 preferably
have those meanings which have already been mentioned as
preferred in connection with the description of the
compounds of the formula (I).
The N-hydroxyacetyl-N-phenyl-ethylglycine (thiol)
esters of the formula (IX) are compounds according to the
invention. They can also be obtained by a procedure in
which
(f) an N-acyloxyacetyl-N~phenyl-ethylgycine (thiol)
ester of the general formula
R3 ~ R~ C - C - Y - R (XII)~
C - CH2 - O - CO - RX
in which
~5 R, Rl, R2 and R3 have the meaning indicated above
and
R8 represents alkyl with 1 to 4 carbon atoms,
is saponified with sodium hydroxide or potassium hydroxide
in aqueous or alcoholic solution, for example in methanol
or ethanol, at a temperature of from 20 to 60C and,
Le A 19 573
5~ ~Z
- 38 -
after acidification wlth a compound o~ the formula (Y),
the saponification product is esterified in the pre~ence
of an esterification catalyst, for example boron tri-
fluoride.
The acyloxyacetylanilides of the formula (XII)
are also compounds according to the instant invention
and can be obtained according to the process variants (a)
resp (d) which are described above.
The formula ~X) provides a general definition of
the halides also to be used as starting materials for
process variant (eXl).In this formula, R6 and Hal pre-
~erably have the meanings indicated in the definition o~
the invention.
The halides of the formula (X~ are generally known
compounds of organic chemistry.
The dihydropyrane also to be used as a starting
substance for process variant (e)(2) is likewise a known
compound of organic chemiætry.
Preferred diluents for the reaction according to
process variant (a) are inert organic solvents. These
include, as preferences, ketones, such as diethyl ketone,
and in particular acetone and methyl ethyl ketone;
nitriles, such as propionitrile 3 and in particular aceto-
nitrile; ethers, such as tetrahydrofuran or dioxan;
aliphatic and aromatic hydrocarbons~ such as petroleum
ether, benzene, toluene or xylene; halogenated hydrocarbons,
~uch as methylene chloride, carbon tetrachloride, chloroform
or chlorobenzene; and esters, such as ethyl acetate.
If appropriate, process variant (a~ can be carried out
in the presence o~ an acid-binding agent EhYdrogen chloride
Le A 19 573
5~39L2
- 39 -
(bromide) accépto~; an~ o~ ~hé cuBtomary acid~bi~ding
agents can be us0d here. These include organic bases~
preferably tertiary amines, for example triethylamine and
pyridine; and furthermore inorganic bases, for example
alkali metal hydroxides and alkali metal carbonates.
A possible catalyst is, in particular, dimethylformamide.
The reaction temperatures can be varied within a
substantial range in carrying out process variant (a).
In general, the reaction is carried out at from 0 to
120C, preferably ~rom 20 to 100C.
In carrying out process variant (a), 1 to 1.5 moles
of the compound of the formula (III) and, if appropriate,
1 to 1.5 moles of acid-binding agent are preferably em-
ployed per mole of the compound of the formula (II), if R
does not represent hydroxyalkyl. However, if R in the
starting compound (II) represents hydroxyalkyl, 2 to 2.5
moles of the compound of the formula (III) and, if appro-
priate, 2 to 2.5 moles of acid-binding agent are employed
per mole of this compound. Isolation of the resulting
compound of the formula (I) is effected in the customary
manner.
Preferred solvents for the reaction according to
process variant (b) are inert organic solvents. These
include, as preferences, aromatic hydrocarbons, such as
benzene, toluene or xylene; halogenated hydrocarbons,
such as chloroform or methylene chloride; esters, such
as ethyl acetate; ethers, such as tetrahydrofuran; or the
actual alcohol (thiol) used as one of the reactants.
Process variant (b) is carried out in the presence
of a condensing agent; any of the customary condensing
agents can be used here, especially dicyclohexylcarbodi-
imide (DCC), chloroformic acid ethyl ester or benzene-
sulphonyl chloride.
The reaction temperatures can be varied within a
substantial range in carrying out process variant (b).
Le
A 19 573
_ 40 -
In general 3 ~he reaction is carried out at from 5 to
150C, preferably from 20 to 100C, or a~ the boiling
point of the solvent used.
In carrying out process variant (b), 2 to 8 moles of
alcohol(thiol) and 1 to 2 moles of condensing agent are
preferably employed per mole of the compound of the formula
(IV). Isolation of the resultant compound of the formula
(I) is effected in the customary manner.
Preferred solvents for the reaction according to
process variant (c) are inert organic solvents. These
include, as preferences, the solvents which have already
been mentioned as preferred for process variant (a).
The reaction can be carried out in the presence of an
organic or inorganic base; preferred bases are stated abo~re
in the paragraph relating to process variant (a).
The reaction temperatures can be varied within a
substantial range in carrying out process variant (c).
In general, the reaction is carried out at from 0 to
120C, preferably from 20 to 100C, or at the boiling
point of the particular solvent. Equimolar amounts of the
reactants are preferably used in carrying out process
variant (c). Isolation of the resultant compound of the
formula (I) is effected in the customary manner.
Preferred diluents for the reaction according to
process variant (d) are inert organic solvents. These
include, as preferences, the solvents which have already
been mentioned for process variant (a).
If appropriate, the reaction according to process
Yariant (d) can be carried out in the presence of an acid-
binding agent. It is possible to add any of the inorganic
or organic acid-binding agents which can customarily be
used, such as an alkali metal carbonate, for example sodium
3o carbonate, potassium carbonate or sodium bicarbonate, or
such as a lower tertiary alkylamine, cycloalkylamine or
aralkylamine, for example triethylamine or dimethyl-
benzylamine, or such as pyridine and diazabicyclooctane.
An excess of azole, when such is used as one of the re~
actants, is preferably used.
Le A 19 573
i3~2
- 41 -
The reaction temperatures`can be varied ~ithin a
substantial range in process variant (~). In ~eneral, the
reaction is carried out at from 20 to 150C~ preferably
at from 60 to 120C. If a solvent is present, the
reaction is appropriately carried out at the boiling
point of the particular solvent.
In carrying out process variant (d), 1 to 2 moles of
the compound of the formula (VIII) and, if appropriate,
1 to 2 moles of acid-binding agent are preferably employed
per mole of the compound of the formula (VII). Isolation
of the compounds of the formula (I) is effected in the
customary manner.
Preferred diluents for the reaction according to
process variant (e) are inert organic solvents. These
include 3 as preferences, the solvents which have already
been mentioned for process variant (a).
If appropriate, the reaction according to process
variant (e)(l) can be carried out in the presence of an
acid-binding agent. It is possible to add any of the
inorganic or organic acid-binding agents which can cus-
tomarily be used. These include, as preferences, the
compounds which have already been mentioned for process
variant (a).
The reaction temperatures can be varied within a
substantial range in process variant (e)(l). In general,
the reaction is carried out at from 20 to 150C, pre-
ferably at the boiling point of the solvent, for example
from 60 to 100~.
In carrying out process variant (e)(l), 1 mole of
halide of the formula (X) and, if appropriate, 1 to 2
moles of acid-binding agent are employed - i~ appropriate
after adding 1 to 2 moles of a strong base, for example
an alkali metal hydride - per mole of the compounds of
the formula (IX~. In order to isolate the end product~
the reaction mixture is freed from solvent, and water and
Le
~ 19 573
i3~2
,,,
- 42 -
an organic solvent are added to thé résidue. The or~anic
phase is separated off and worked up in thé customary
manner.
According to a preferred embodiment of the process
variant (e3(1), an appropriate procedure is to use a
hydroxyacetanilide of the formula (IX) as the starting
material, to convert this compound into the alkali metal
alkanolate in a suitable inert solvent by means of an
alkali metal hydride or bromide and to react this alkanolate
immediately, without isolation, with a halide of the formula
(X), the resultant compound of the formula (I) being
obtained in one operation, with elimination of an alkali
metal halide.
If appropriate, the reaction according to process
variant (e)(2) can be carried out in the presence of a
catalyst. Hydrogen chloride is preferably used'for this
~see J.Am.Chem.Soc. 69, 2246 (1947), and ib'ido''70, 41~7
(1948)).
The reaction temperatures can be varied within a
substantial range in process variant (e)(2). In general,
the reaction is carried out at from 0 to 100C, preferably
from 20 to 60C.
Equimolar amounts of the reactants are preferably
used in carrying out process variant (e)(2). Isolation of
the resultant compound of the formula (I) is effected in
the customary manner.
The active compounds according to the invention
exhibit a powerful microbicidal action and can be employed
in practice for combating undesired micro-organisms.
The active compounds are suitable for use as plant pro-
tection agents.
Fungicidal agents in plant protection are employed
for combating Plasmo'dio~h'oromy~cetes~ o'mycetes ? Chy't'ridio-
m~ce'tes, ~ ,''A's'c'o'my'c'e:tes,' B'a's'i'd'i'o'myc'et'es and
e'u't'e'r'o'my'c'e't'es.
Le A 19 573
53~2
- IJ3 -
The good toleration, by plants, Or the actiYe com-
pounds, at the concentrations required ~or combating
plant diseases, permits treatment of above-ground parts of
plants, of vegetative propagation stock and seedsJ and of
the soil.
As plant protection agents, the active compounds
according to the invention can be used with particularly
good success for combating Oomycetes, for example the
pathogen of blight and brown rot of tomato and potato
10 (Phy'to'phthora'infestans). It should be particularly -
emphasised that the active compounds according to the
invention not only develop a protective action but also
a curative/eradicative action. They also have systemic
properties. Thus, it is possible to protect plants
against fungal attack when the active compound is fed to
the above-ground parts of the plant via the soil and the
root or via the seed.
The active compounds can be converted into the
customary formulations, such as solutions, emulsions,
suspensions, powders, dusting agents, foams, pastes,
soluble powders, granules, aerosols, suspension-emulsion
concentrates, seed-treatment powders 3 natural and
synthetic materials impregnated with active compound,
very fine capsules in polymeric substances, coating
compositions for use on seed, and formulations used
with burning equipment, such as fumigating cartridges,
fumigating cans and fumigating coils, as well as ULV
cold mist and warm mist formulations.
These formulations may be produced in known manner~
for example by mixing the active compounds with extenders,
that is to say liquid ~r liquefied gaseous or solid
diluents or carriers, optionally with the use of surface-
active agents, that is to say emulsifying agents andtor
dispersing agents and/or foam-forming agents. In
the case of the use of water as an extender, organic
Le ~ 19 573
S3~2
- 44 -
solvents can, for example, also be used as au%iliary
solvents.
As liquid diluents or carriers, especially
solvents, 5here are suitable in the main, aromatic
hydrocarbons, such as xylene, toluene or alkyl naphthalenes,
chlorinated aromatic or chlorinated aliphatic hydrocarbons,
such as chlorobenzenes, chloroethylenes or methylene
chloride, aliphatic or alicyclic hydrocarbons, such
as cyclohexane or paraffins, for example mineral
oil fractions, alcohols, such as butanol or glycol
as well as their ethers and esters, ketones, such
as acetone~ methyl ethyl ketone, methyl isobutyl
ketone or cyclohexanone, or strongly polar solvents~
such as dimethylformamide and dimethylsulphoxide,
as well as ~ater.
By liquefied gaseous diluents or carriers are
meant liquids which would be gaseous at normal temperature
and under normal pressure, for example aerosol propellants,
such as halogenated hydrocarbons as well as butane,
propane, nitrogen and carbon dioxide.
As solid carriers there may be used ground
natural minerals, such as kaolins, clays, talc,
chalk, quartz, attapulgite, montmorillonite or diatomaceous
earth, and ground synthetic minerals, such as highly-
dispersed silicic acid, alumina and silicates. Assolid carriers for granules there may be used crushed
and fractionated natural rocks such as calcite,
marble, pumice, sepiolite and dolomite, as well
as synthetic granules of inorganic and organic meals,
3o and granules of organic material such as sawdust~
coconut shells, maize cobs and tobacco stalks.
As emulsifying and/or foam-forming agents there
may be used non-ionic and anionic emulsifiers, such
as polyoxyethylene-fatty acid esters, polyoxyethylene-
fatty alcohol ethers, for example alkylaryl polyglycol
Le A 19 573
~1~53
- 45 -
ethers, alkyl sulphonates, alkyl sulphates, aryl sulphona~es
as well as albumin hydrolysis products. Dispersing
agents include, for example, lignin sulphite waste
liquors and methylcellulose.
Adhesives such as carboxymethylcellulose and
natural and synthetic polymers in the form Or powders,
granules or latices, such as gum arabic, polyvinyl
alcohol and polyvinyl acetate, can be used in the
formulations.
It is possible to use colorants such as inorganic
pigments, for example iron oxide, titanium oxide and
Prussian Blue, and organic dyestuffs, such as alizarin
dyestuffs, azo dyestuffs or metal phthalocyanine
dyestuffs 3 and trace nutrients, such as salts of
iron, manganese, boron, copper, cobalt, molybdenum
and zinc.
The formulations in general contain from 0.1
to 95 per cent by weight of active compound, preferably
from 0.5 to 90 per cent by weight.
The active compounds according to the invention can
be present in the formulations or in the various use forms
as a mixture with other active compounds, such as fungi-
cides, bactericides, insecticides, acaricides, nematicides,
herbicides, bird repellants, growth factors~ plant
nutrients and agents for improving soil structure.
The active compounds can be used as such or in the
form of their formulations or the use forms prepared
therefrom by further dilution, such as ready-to-use
solutions, emulsions, suspensions, powders, pastes and
~0 granules. They may be used in the customary manner, for
example by watering, immersion, spraying, atomising,
misting, vaporising, injecting, forming a slurry, brushing
on, dusting, scattering, dry dressing, moist dressing, wet
dressing, slurry dressing or encrusting.
Le A 19 ~7~
- 46 -
Especially in the treatment of parts of plants, the
active compound concentrations in the use forms can be
varied within a substantial range They are, in general,
from 1 to 0.0001% by weight, preferably from 0.5 to
0.001%.
In the treatment of seed, amounts of active com-
pound of 0.001 to 50 g, preferably 0.01 to 10 g, are
generally employed per kilogram of seed.
For the treatment of soil, active compound con-
centrations of 0.00001 to 0.1% by weight, preferably
0.0001 to 0.02%, are generally employed at the place of
action.
The present invention also provides a fungicidal
composition containing as active ingredient a compound
of the present invention in admixture with a solid
or liquefied gaseous diluent or carrier or in admixture
with a liquid diluent or carrier containing a surface-
active agent.
The present invention also provides a method
of combating fungi which comprises applying to the
fungi , or to a habitat thereof, a compound of the
present invention alone or in the form of a composition
containing as active ingredient a compound of the
present invention in admixture with a diluent or
carrier.
The present invention further provides crops
protected from damage by fungi by being grown in areas
in which immediately prior to and/or during the time
of the growing a compound of the present invention
was applied alone or in admixture with a diluent
or carrier.
It will be seen that the usual methods of providing
a harvested crop may be improved by the present invention.
m e fungicidal activity of the compounds of
this invention is illustrated by the following biotest
Le A 19 573
5~2
- 47 -
Examples.
In these Examples, the compounds according to
the present invention are each identified by the number
(given in brackets) of the corresponding preparative
Example, which will be found later in this specification.
The known comparison compound~ are identified
as follows:
n
,__<CH3 CH2- C - O - CH~
(A) = ~ ~ C - CH2Cl
CH3
N-chloroacetyl-N-(2,6-xylyl)-glycine methyl ester
(B) = ~ CH~ 0
C2H5 ~ - CH2Cl
N-chloroacetyl-N-(2-ethyl-6-methylphenyl)-alanine methyl
ester
Example A
~ test (tomato)/protective
Solvent: 4.7 parts by weight of acetone
Emulsifier: 0.~ part by weight of alkylaryl polyglycol
ether
Water: 95 parts by weight
The amount of the active compound required for
the de8ired concentration of the active compound in
the spray liquid was mixed with the stated amount
of solvent and the concentrate was diluted with the
stated amount of water which contained the stated
~e A 19 57~
~53~2
- 48 -
amount of emulsifier.
Young tomato plants with 2 to 4 foliage 'leaves
were sprayed with the spray liquid until dripping
wet. The plants remained in a greenhouse for 24
hours at 20 deg.C and at a relative atmospheric humidity
of 70%. The tomato plants were then inoculated with
an aqueous spore suspension of Phyto'p'h't'h'o'ra'i~fe's't'ans.
The plants were brought into a moist chamber with
an atmospheric humidity of 100% and a temperature
10 of 18-20 deg.c.
After 5 days the infection of the tomato plants
was determined. The assessment data were converted
to percent infection: 0% meant no infection; 100%
meant that the plants were totally infected~
In this test, for example, the following compounds
exhibited a very good action which was significantly
superior to that of the compounds (A) and (B) known from
the prior art: compounds (12), (1) and (10).
Example B
20 Phytophthora test (tomato)/systemic
Solvent: 4.7 parts by weight of acetone
Emulsifier: 0~3 part by weight of alkylaryl polyglycol
ether
Water: 95 parts by weight
The amount of active compound required for the
desired concentration of the active compound in the
watering liquid was mixed with the stated amount
of solvent and the concentrate was diluted with the
stated amount of water which contained the stated
30 amount of the emulsifier.
Tomato plants grown in standard soil and having
2 to 4 foliage leaves were watered three times in
the course of one week with 10 ml of the watering
liquid, having the stated concentration of active
35 compound, per 100 ml of soil.
Le A 19 573
~s~
- 49 -
The plants -treated in this way were inoculated~
after the treatment, with an aqueous spore suspension
of Phytoph'thora'infestans. The plants were brought
into a humidity chamber at an atmospheric humidity of
100% and a temperature of 18 to 20 deg.C. After 5
days, the infection of the tomato plants was determined.
The assessment data obtained were converted to percent
infection. 0~ denoted no infection and 100% denoted
that the plants were totally infected.
In this test, for example, the following compounds
exhibited a very good action which was significantly
superior to that of the compound (B) known from the prior
art: compounds (12), (1), (2), (8) and (10).
Preparative Examples
15 E~xa~ple 1
C2 H5 ,~,
C~3 I H - C - OCH3 ( 1 )
CH3 C - CH2 - O - CH3
o
Process variant (a)
13.3 g (0.122 mol) of methoxyacetyl chloride were
added dropwise to a solution of 18.4 g (0.0816 mol) of
20 N-(2,6-xylyl)-ethylglycine methyl ester and a few drops
of dimethylformamide in 80 ml of toluene at room tempera-
ture and the mixture was stirred at 80 C for 3 hours.
After cooling, the solution was diluted with ethyl acetate,
washed wi~h dilute hydrochloric acid, water and sodium
25 bicarbonate solution, dried over sodium sulphate and evaporated.
The residue was crystallised from ligroin. 10.4 g (43.5%
of theory) of N-methoxyacetyl-N-(2~6-xylyl)-ethylglycine
methyl ester of melting point 96~97C were obtained~
.
CH3 ~2H~
~ ~ CH - 8 O~H3
~u H
.,..~
Le A 19 573
3~2
- 50 -
A mixture Or 3~7.3 g ~2,l.mol) o~ 2~b.romobutyric
acid methyl eæter, 127.0 g (1.05 mol) o~ 2',6-xylidine,
121 8 g (2.1 mol) of potassium fluoride and 100 ml of
dimethylformamide was stirred at 100C under nitrogen for
39 hours. After cooling, it was filtered, the filtrate
was poured into water, the oil which had separated out was
extracted with methylene chloride and the extract was
washed with water J dried over sodium sulphate and
evaporated The residue was fractionated over a column,
in vac'uo. 112.0 g (48.3% of theory) of N-(2,6-xylyl)-
ethylglycine methyl ester o~ boiling point 100-110C/0.9
mbar were obtained.
E~ample 2
2Hg f1
N/ 3 (2)
CH3 C - CH2 - N
Process variant (a?
18.4 g of pyrazol-l-yl-acetyl chloride hydrochloride
(prepared from 0.1 mol of pyrazol-l-yl-acetic acid~
were introduced into a solution, boiling under reflux,
of 11.1 g (0.05 mol) of N-(2,6~xylyl)-ethylglycine
methyl ester, 7.9 g (0.1 mol) of pyridine and 1.2 g (0.01
mol) of 4-dimethylaminopyridine in the cour~e o~ 35
minutes and the mixture was heated under reflux for
22 hours. The reaction mixture was evaporated in va~uo,
the residue was partitioned between ethyl acetate and 1
molar citric acid and the or~anic pha~e was washed with 5
strength sodium hydroxide solution and water, dried over
sodium sulphate and concentrated.. The res.idue wa
crystalliæed from to.luene/petroleum ether (1:4). 11.3 g
(68.7~ ~ theory) of N-(pyrazol-l-yl-acetyl)-N~(2,6-xylyl)-
ethylglycine methyl ester of.me.lting point 113~115C were
obtained.
Le A 19 573
.,
5~34Z
- 51 -
P~e'pa'~ ~
.
Cl - C - CH2 - N J x HCl
~N
One drop of dimethylformamide was added to a sus-
pension of 12.6 g (0.1 mol) of pyrazol-l-yl-acetic acid
in 40 ml of toluene, and 19.05 g (0.15 mol) of oxalyl
chloride were added dropwise at 25-30~ (cooling with ice).
After stirring the mixture at room temperature for 17
hours, it was filtered and the residue was boiled down
twice with toluene. 18.4 g of crude pyrazol-l-yl-acetyl
chloride hydrochloride, which could be employed further
without purification, were obtained.
Example 3
CH - C - OCH3
CH~ C - CH2 - OH
O ..
Proc-ess variant (f)
.
A solution of 21.3 g (0,38 mol) of powdered potassium
hydroxide in 200 ml of methanol was added dropwise to a
solution of 61.1 g (0.19 mol) of N-acetoxyacetyl-N-(2,6-
xylyl)-ethylglycine methyl ester in 200 ml of methanol at
room temperature in the course of 15 minutes and the
mixture was stirred at room temperature for 1 hour and
at 50C for 3.5 hours. The reaction solution was
evaporated, the aqueous solution of the residue was ex-
tracted by shaking with ether and the product phase was
acidified with half-concentrated hydrochloric acid and
extrac~d with ethyl acetate. The extract was dried over
sodium sulphate and evaporated.
Le' A 19 573
- 52 -
The residue was dissolved in 180 ml of methanol àn~3
after adding 81.0 g (0.571 mol) of boron trifluoride
etherate (48% strength), the mixture was heated under
reflux for 17 hours. The reaction solution was poured
into 1,000 Ir.l of 10% strength sodium bicarbonate solution,
whilst cooling with ice, the mixture was extracted several
times with methylene chloride and the extract was washed
with water, dried over sodium sulphate and evaporated.
48 1 g (90.6% of theory) of N-hydroxyacetyl-N-(2,6-xylyl)-
10 ethylglycine methyl ester of melting point 101-102C were
obtained .
- Example 4
. . _ .
IC2 H5 0
(~--N\ (4)
CH3 ,C, - CH2 ~ 0 - S02 - CH3
Process variant (e)(l)
11.5 g (0.1 mol) of methanesulphonic acid chloride
were added dropwise to a solution of 13.95 g (0.05 mol)
of N-hydroxyacetyl-N-(2,6-xylyl)-ethylglycine methyl ester
(Example 3) and 12.3 g (0.11 mol) of 1,4-diazabicyclo[2,2,2]-
octane in 150 ml of methylene chloride at 20-25C (cooling
20 with ice) and the mixture was stirred at room temperature
for 17 hours. The reaction solution was washed with water,
with 10% strength aqueous pyridine, with dilute hydrochloric
acid and with water, dried over sodium sulphate and
evaporated. The residue was crystallised from ligroin/
25 toluene (7:2). 13~9 g (78~8% of theory) of N-methane-
sulphonyloxyacetyl-N-(2,6-xylyl)-ethylglycine methyl ester
of melting point 92C were obtained.
Examp le 5
, . .
CH Cl -OCH
CH3 ~CI - CH2 _ o _
O O
Process variant (e)(2)
Le A 19 573
34~
4 ml of 1 molar ethereal hydrogen chloride were added to a l~ixture of
11.2 g (0.04 mol) of N-hydroxyacetyl-N-(2,6-xylyl~-ethylglycine methyl ester
(Example 3) and 13.8 g (0.16 mol) of 3,4-dihydro-2H-pyrane, and the mixture ~,7as
stirred at room temperature for 23 hours. After dilution with ethyl acetate,
the mixture was washed with sodium bicarbcnate solution and water, dried over
sodium sulphate and evaporated and the oily residue was freed from volatile
impurities using an oil pump. 14.4 g (99.2~ of theory) of N-tetrahydro-
pyranyloxyacetyl-N-(2,6-xylyl)-ethylglycine methyl ester were obtained as an oil
with the refractive index nD = 1.4959.
The follcwing ccmpounds of the general formula :
R2 Rl IC2H5 11
~ ~ CH - C - Y - R
R3~ ~ \ C R4 (I)
were obtained in an analogous manner.
o~
- ~ o
~ ~ ~ a ~, a a~ , a O
~; ~
~ o o o o o o o o o
~ ~ Z~
~o ~ r ~~7 ~
~; P~ X
~ ~: X
-- 54 --
.,~
