CA1154770A - Process for the preparation of 2-methylene- quinoxaline-1,4-dioxide derivatives - Google Patents
Process for the preparation of 2-methylene- quinoxaline-1,4-dioxide derivativesInfo
- Publication number
- CA1154770A CA1154770A CA000385733A CA385733A CA1154770A CA 1154770 A CA1154770 A CA 1154770A CA 000385733 A CA000385733 A CA 000385733A CA 385733 A CA385733 A CA 385733A CA 1154770 A CA1154770 A CA 1154770A
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- general formula
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- hydroxyl
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/50—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to ring nitrogen atoms
- C07D241/52—Oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
ABSTRACT
The invention relates to a process for the prapara-ion of 2-methylene-1,4-dioxide derivatives of the general formula /I/
wherein A represents a hydroxyl or an amino group, or a group of the general formula -NH-COOR1, wherein R1 denotes a C1-4 alkyl group;
or a group of the general formula -NH-CX-NH2, wherein X
stands for oxygen or sulfur;
or a group of the formula -NH-C/=NH/-NH2;
or a group of the general formula -NH-R2, wherein R2 represents C1-6 alkyl, ohenyl, benzyl, hydroxyl or hydroxy-/C2-4 alkyl/;
or a group of the general formula -NH-CO-R3, wherein R3 stands for a C1-20 alkyl group, a phenyl group optionally substituted by one, tno or three identical or different substituent/s/ selected from the group consisting of hydroxyl, amino, nitro, C1-4 alkyl, C1-4 alkoxy or halogen; a piperidyl, a pyridyl, a furyl, a nitro-furyl, a pyrazinyl, a pyrimidyl, a naphthyl, a hydroxy-naphthyl, a phenylalkyl, an 1,2,4-triazinyl, an .alpha.,.alpha.--diphenyl-.alpha.-hydroxymethyl, a cyanomethyl, a halomethyl or a hydroxymethyl group, characterized by dehydrating a compound of the general formula /II/
wherein A has the same meanings as above.
The compounds of the general formula /I/ possessing bactericidal and weight-gain increasing properties can be obtained in a high purity with an excellent yield by the process according to the invention.
The invention relates to a process for the prapara-ion of 2-methylene-1,4-dioxide derivatives of the general formula /I/
wherein A represents a hydroxyl or an amino group, or a group of the general formula -NH-COOR1, wherein R1 denotes a C1-4 alkyl group;
or a group of the general formula -NH-CX-NH2, wherein X
stands for oxygen or sulfur;
or a group of the formula -NH-C/=NH/-NH2;
or a group of the general formula -NH-R2, wherein R2 represents C1-6 alkyl, ohenyl, benzyl, hydroxyl or hydroxy-/C2-4 alkyl/;
or a group of the general formula -NH-CO-R3, wherein R3 stands for a C1-20 alkyl group, a phenyl group optionally substituted by one, tno or three identical or different substituent/s/ selected from the group consisting of hydroxyl, amino, nitro, C1-4 alkyl, C1-4 alkoxy or halogen; a piperidyl, a pyridyl, a furyl, a nitro-furyl, a pyrazinyl, a pyrimidyl, a naphthyl, a hydroxy-naphthyl, a phenylalkyl, an 1,2,4-triazinyl, an .alpha.,.alpha.--diphenyl-.alpha.-hydroxymethyl, a cyanomethyl, a halomethyl or a hydroxymethyl group, characterized by dehydrating a compound of the general formula /II/
wherein A has the same meanings as above.
The compounds of the general formula /I/ possessing bactericidal and weight-gain increasing properties can be obtained in a high purity with an excellent yield by the process according to the invention.
Description
' L~ NE -This invention relates ~o a new proCess for the prepara~ion of 2~methylene-quinoxaline-1,4-dioxide derivatives known to possass bac~ericidal and wei3ht~gain increasing effects. The compounds prepared accordirlg ~o ~he inv~ntion are encompassed by ~he general formula /I/
,~\~ N y CH ~ A
wherein A represents a hydroxyl or an am~no group, or a group of the general formula -NH COORl, wherein R
denotos a Cl 4 alkyl group;
or a group of the general formula -NH-CX-NH2, wherein X
stands for oxygen or sulfur;
or a group o~ the formulal -NH-C/=NH/-NH2;
or a group of the general formula -NH-R2~ wherein R2 represents Cl 6 alkyl, phenyl, benzyl, hydroxyl or hydroxy--/C2_4 alkyl/;
or a group of the general formula -NH-C0-R3, wherein R3 stands for a Cl 20 alkyl group, a phonyl group optionally substituted by one, ~wo or three iden~ical or different substituent/s/ selected from the group consisting of A2310-62 ~ ~.
.. . .
~5~7~7~
~ 2 --hydroxyl, amino, ni~ro, Cl ~ alkyl, Cl 4 alkoxy or halogen;
a piperîdyl, a pyridyl, a furyl, a nitrofuryl, a pyraz1nyl, a pyrimidyl, a naphthyl, a hydroxynaphthyl, a phenylalkyl, an 1,2,~-triazinyl, an ~,~ ~diphenyl- ~-hydroxymethyl, a cyanomethyl a halomethyl or a hydroxymethyl group~
The ~erm "alkyl group" used in the specification and claims covars straight-chained or branched saturated aliphatic hydrocarbyl groups, such a5 methyl,ethyl, n-propyl, isopropyl, n-butyl, sec~-butyl, tert,-butyl, etc. The term "alkoxy group"
refers to groups derived from the alkyl groups mentioned above, such as methoxy, ethoxy, n-propoxy, isopropoxy, n--butoxy, etc, Preferred representatives of the "hydroxy--/C2 4 alkyl/" groups are the hydroxyethyl, hydroxypropyl, hydroxyisopropyl and ~he hydroxybutyl groups. The term - 15 "halogen" may stand for all the four halogen a~oms, such as fluorine, chlorine, bromine and iodine. The term "haIo-methyl group" refers to methyl groups substituted by a halogan atom, such as fluoromethyl, chloromethyl, ~bromo-ethyl and iodomethyl, It is known from the U5 patent specification Nos~
3,371,090 and 3,493,572 tha~ the compounds of ~he general formula /I/ can be prepared by reacting 2-formyl-quinoxaline--1~4-dioxide or the diallcyl-acetal ~hereof with a reactan~
containing a primary amino groupO The reac~ion i5 un~avourable because of the moderate yield /about 80 J0/ and tha relatively long reaction time, which in csrtain cases, can be as long as 24 hours. Besides, tha main reaction is accompanied by different side-reactions, and the desired compound is ~ ~59~
~ 3 -:
contaminàted with the side-products ~hus-formedO The puri-fication of the end-product requires complica~ed operations and can be carried ou~ only a~ the expense of high losses of substance, According to a fur~her known method the co~pounds of the general formula /I/ are produced by reacting 2~formyl--quinoxaline-1,4-dioxide or the corresponding dialkyl-acetal with a Schiff base /Hungarian pa~ent specification No, 171,738/~
~ Now i~ has been found that the compounds of the general formula /I/ can be prepared economically in an excellent purity by dehydrating a Z-hydroxyme~h~ quinoxaline-1,4--dioxide derivative o~ the general formula /II/
O OLI
C~I-Nl-l-A
wherein A has the same meanings as above, The dehydration can be carried out in two different ways: either thermally, that is by heating the compound of the general formula /II/, or by using a dehydrating agent~
When dehydrating under thermic conditions one prooeeds preferably by heating the suspension of the compound of the general formula /II/ in an indifferent solvent until no more water is split off, As indifferent solvent preferably water, aliphatic alcohols, such as isopropanol or butanol, aromatic hydrocarbons, such as toluene or xylene can be used. The ~;~
47~3 ~ 4 -reaction is preferably carried out at the boiling poin~
of the solvent, generally at 40 C ~o 150 C~ When using an organic solv~nt immiscible with water the ~ermal dehydration can be carried ou~ by continually removing the water obtained -From the system, e.g. in form of an azeotrope, In this way the reaction can be followed, too, When dehydra~ing according to the o~her metl70d, de-hydrating agents generally used ~or such purpose /eOg, polyphosphoric acid, sulfuric acid, calcium chloride, etc./ are used, The 2-hydroxymethyl-quinoxaline-1,4-dioxide dertvatives of the general formula /II~ used as starting substances are new compounds which can be prepared by reacting a Z-methylene--quinoxaline-1,4-dioxide derivative of the genaral formula ~N ~,CH - Q
wherein Q represents an oxygen atom or two alkoxy groups containing 1-4 carbon atoms each, with a carboxylic hydrazine of the gsneral formula /IV/
A NH2 /~V/
wherein A has the same meanings as above, As the dehydration of the compounds of the general -- 5 ~
formula /IIJ is carried ou~ quickly, the side-product formation is eliminated and the compounds of the general formula /I/ can be obtained economically, almost quantita-tively.
Further details of the ~nvention are illustrated by the following non-limiting Examples:
~ s of the general formula 091 mole of 2-formyl~quinoxaline-1,4-di~xide dissolved in water or dimethylformamide is reacted with 0~1 mole of a compound of the general formula /IV/ in the presence of 2 drops of concentrated hydrochloric acid or piperidine. The separated product is ~iltered off, washed wlth water and dried.
~e~L
~9 28.0 9 /0.1 mole/ of 2-/~C-/methoxycarbonyl-hydrazino/--o~-hydroxymethyl/-quinoxaline-1,4-dioxide are admixed with 150 ml of water and the mixture is boiled for an hour under stirring. Then it is cooled, the separated prodwct is filtered off and washed with water. 25,4 g /98 ,~0~ of desired compound are obtained.
~.p~: 257-258 C.
Example 2 ~
41,6 g /o.l mole/ of 2-/ ~/3,4,5-~rimethoxybenzoyl-5 -hydrazino/- -hydroxyme~hyl/-quinoxaline-1,4-clioxide are dehydrated in 250 ml of isopropanol, in the presence of a drops of sulfuric acid at 50 C to 60 C, under stirring, After cooling the reaction mixture the separa~ed product is filtered off and washed~ 39~R g /98 %/ of desired compound are obtained. M~p,: 255-256 C, Example 3 -1,4-dioxide -27.2 g /Ool mole/ of 2-/Oc-/cyanoacetyl-hydrazono--- ~-hydroxymethyl/-quinoxaline-1,4-dioxide are suspended in 200 ml of toluene, and the reaction mix~ure is kept alt 1;20 C ~or an hour, Then it is cooled, and ~he separated product is filtered of~, 26,0 9 ~97 t,Y~/ of desired compound 20 are obtained, M,p.: 244-245 C
Example 4
,~\~ N y CH ~ A
wherein A represents a hydroxyl or an am~no group, or a group of the general formula -NH COORl, wherein R
denotos a Cl 4 alkyl group;
or a group of the general formula -NH-CX-NH2, wherein X
stands for oxygen or sulfur;
or a group o~ the formulal -NH-C/=NH/-NH2;
or a group of the general formula -NH-R2~ wherein R2 represents Cl 6 alkyl, phenyl, benzyl, hydroxyl or hydroxy--/C2_4 alkyl/;
or a group of the general formula -NH-C0-R3, wherein R3 stands for a Cl 20 alkyl group, a phonyl group optionally substituted by one, ~wo or three iden~ical or different substituent/s/ selected from the group consisting of A2310-62 ~ ~.
.. . .
~5~7~7~
~ 2 --hydroxyl, amino, ni~ro, Cl ~ alkyl, Cl 4 alkoxy or halogen;
a piperîdyl, a pyridyl, a furyl, a nitrofuryl, a pyraz1nyl, a pyrimidyl, a naphthyl, a hydroxynaphthyl, a phenylalkyl, an 1,2,~-triazinyl, an ~,~ ~diphenyl- ~-hydroxymethyl, a cyanomethyl a halomethyl or a hydroxymethyl group~
The ~erm "alkyl group" used in the specification and claims covars straight-chained or branched saturated aliphatic hydrocarbyl groups, such a5 methyl,ethyl, n-propyl, isopropyl, n-butyl, sec~-butyl, tert,-butyl, etc. The term "alkoxy group"
refers to groups derived from the alkyl groups mentioned above, such as methoxy, ethoxy, n-propoxy, isopropoxy, n--butoxy, etc, Preferred representatives of the "hydroxy--/C2 4 alkyl/" groups are the hydroxyethyl, hydroxypropyl, hydroxyisopropyl and ~he hydroxybutyl groups. The term - 15 "halogen" may stand for all the four halogen a~oms, such as fluorine, chlorine, bromine and iodine. The term "haIo-methyl group" refers to methyl groups substituted by a halogan atom, such as fluoromethyl, chloromethyl, ~bromo-ethyl and iodomethyl, It is known from the U5 patent specification Nos~
3,371,090 and 3,493,572 tha~ the compounds of ~he general formula /I/ can be prepared by reacting 2-formyl-quinoxaline--1~4-dioxide or the diallcyl-acetal ~hereof with a reactan~
containing a primary amino groupO The reac~ion i5 un~avourable because of the moderate yield /about 80 J0/ and tha relatively long reaction time, which in csrtain cases, can be as long as 24 hours. Besides, tha main reaction is accompanied by different side-reactions, and the desired compound is ~ ~59~
~ 3 -:
contaminàted with the side-products ~hus-formedO The puri-fication of the end-product requires complica~ed operations and can be carried ou~ only a~ the expense of high losses of substance, According to a fur~her known method the co~pounds of the general formula /I/ are produced by reacting 2~formyl--quinoxaline-1,4-dioxide or the corresponding dialkyl-acetal with a Schiff base /Hungarian pa~ent specification No, 171,738/~
~ Now i~ has been found that the compounds of the general formula /I/ can be prepared economically in an excellent purity by dehydrating a Z-hydroxyme~h~ quinoxaline-1,4--dioxide derivative o~ the general formula /II/
O OLI
C~I-Nl-l-A
wherein A has the same meanings as above, The dehydration can be carried out in two different ways: either thermally, that is by heating the compound of the general formula /II/, or by using a dehydrating agent~
When dehydrating under thermic conditions one prooeeds preferably by heating the suspension of the compound of the general formula /II/ in an indifferent solvent until no more water is split off, As indifferent solvent preferably water, aliphatic alcohols, such as isopropanol or butanol, aromatic hydrocarbons, such as toluene or xylene can be used. The ~;~
47~3 ~ 4 -reaction is preferably carried out at the boiling poin~
of the solvent, generally at 40 C ~o 150 C~ When using an organic solv~nt immiscible with water the ~ermal dehydration can be carried ou~ by continually removing the water obtained -From the system, e.g. in form of an azeotrope, In this way the reaction can be followed, too, When dehydra~ing according to the o~her metl70d, de-hydrating agents generally used ~or such purpose /eOg, polyphosphoric acid, sulfuric acid, calcium chloride, etc./ are used, The 2-hydroxymethyl-quinoxaline-1,4-dioxide dertvatives of the general formula /II~ used as starting substances are new compounds which can be prepared by reacting a Z-methylene--quinoxaline-1,4-dioxide derivative of the genaral formula ~N ~,CH - Q
wherein Q represents an oxygen atom or two alkoxy groups containing 1-4 carbon atoms each, with a carboxylic hydrazine of the gsneral formula /IV/
A NH2 /~V/
wherein A has the same meanings as above, As the dehydration of the compounds of the general -- 5 ~
formula /IIJ is carried ou~ quickly, the side-product formation is eliminated and the compounds of the general formula /I/ can be obtained economically, almost quantita-tively.
Further details of the ~nvention are illustrated by the following non-limiting Examples:
~ s of the general formula 091 mole of 2-formyl~quinoxaline-1,4-di~xide dissolved in water or dimethylformamide is reacted with 0~1 mole of a compound of the general formula /IV/ in the presence of 2 drops of concentrated hydrochloric acid or piperidine. The separated product is ~iltered off, washed wlth water and dried.
~e~L
~9 28.0 9 /0.1 mole/ of 2-/~C-/methoxycarbonyl-hydrazino/--o~-hydroxymethyl/-quinoxaline-1,4-dioxide are admixed with 150 ml of water and the mixture is boiled for an hour under stirring. Then it is cooled, the separated prodwct is filtered off and washed with water. 25,4 g /98 ,~0~ of desired compound are obtained.
~.p~: 257-258 C.
Example 2 ~
41,6 g /o.l mole/ of 2-/ ~/3,4,5-~rimethoxybenzoyl-5 -hydrazino/- -hydroxyme~hyl/-quinoxaline-1,4-clioxide are dehydrated in 250 ml of isopropanol, in the presence of a drops of sulfuric acid at 50 C to 60 C, under stirring, After cooling the reaction mixture the separa~ed product is filtered off and washed~ 39~R g /98 %/ of desired compound are obtained. M~p,: 255-256 C, Example 3 -1,4-dioxide -27.2 g /Ool mole/ of 2-/Oc-/cyanoacetyl-hydrazono--- ~-hydroxymethyl/-quinoxaline-1,4-dioxide are suspended in 200 ml of toluene, and the reaction mix~ure is kept alt 1;20 C ~or an hour, Then it is cooled, and ~he separated product is filtered of~, 26,0 9 ~97 t,Y~/ of desired compound 20 are obtained, M,p.: 244-245 C
Example 4
2~
4.16 g /0.01 mole/ of 2-/~ -/3',4',5'-trimethexy-benzoyl-hydrazino/~ hydroxymethyl/-quinoxaline-1,4--dioxide mixed with 40 g of polyphosphoric aciLd are allowed to react a~ 25 C for 3 hours, ~hen the reac~ion micture is poured into a lo % cold sodium hydroxide solution, The separated precipita~e is ~iltered o~f and washed wi~h water until neu~ral. 38.6 9 /97 ~/ o~ desired compound are obtained.
M,p.: 256-256.5 ~C.
The compounds listed in the following Table are prepared by the methods o~ the previous Examples:
5gL7~71~
n ~ cn In ~ n ~ In i~a~ co ~ N ~1 (:~ ~ N O
. ~ ~ m ~ ~a~
Q C) I I I I I I I -r I I I I I I
O )a) ~ O CD r~ lcn u) o OD ~ 0~ ~ ~Ln ~ O ~ i~ Da) ~o ~IC`l N N~IC'J NrJ N N ~1 C~l ~J C\l C~l C~l ~J u~ o m o m m m ~ ~ ~ o~ ~ ~ ~ mco L C~ I o I ~ I I o I I o o o O o O o o o Ou) o o o O ~o o O In m Ln N ~ LnIn E 0~ COcnCO ~ U)t~
~1) Y- _I
O O~I N ~1_I~1~I N ~ 1 ~ N ~t a~ o x ~1 O
~1 ~:
E r Q ~ ~I
4.16 g /0.01 mole/ of 2-/~ -/3',4',5'-trimethexy-benzoyl-hydrazino/~ hydroxymethyl/-quinoxaline-1,4--dioxide mixed with 40 g of polyphosphoric aciLd are allowed to react a~ 25 C for 3 hours, ~hen the reac~ion micture is poured into a lo % cold sodium hydroxide solution, The separated precipita~e is ~iltered o~f and washed wi~h water until neu~ral. 38.6 9 /97 ~/ o~ desired compound are obtained.
M,p.: 256-256.5 ~C.
The compounds listed in the following Table are prepared by the methods o~ the previous Examples:
5gL7~71~
n ~ cn In ~ n ~ In i~a~ co ~ N ~1 (:~ ~ N O
. ~ ~ m ~ ~a~
Q C) I I I I I I I -r I I I I I I
O )a) ~ O CD r~ lcn u) o OD ~ 0~ ~ ~Ln ~ O ~ i~ Da) ~o ~IC`l N N~IC'J NrJ N N ~1 C~l ~J C\l C~l C~l ~J u~ o m o m m m ~ ~ ~ o~ ~ ~ ~ mco L C~ I o I ~ I I o I I o o o O o O o o o Ou) o o o O ~o o O In m Ln N ~ LnIn E 0~ COcnCO ~ U)t~
~1) Y- _I
O O~I N ~1_I~1~I N ~ 1 ~ N ~t a~ o x ~1 O
~1 ~:
E r Q ~ ~I
3 L 0 L L L L o Ll_ o _I L~D L o L
,1 ~ Q G) ~GlID La~ ~ C o al C ~ C Q~
O ~JJ~JJJ Q ~
~D ~ L 0 ~ 0 ~ O ~ 0 C 11) ~~1 ~ S:t3 ~: ~ O ~ X ~ O~
O) E.1:1 E
.,1 >`
N ~I N
I ~ J ~ N O
I ~ rl ~ O I I --1~! I N I U~ I
Z IUl L O r Q Q >~ N I N
d ~ ~i9 3 d o ILn l~n ~ ~ Im ~ ILn ~ Im O O ~1 0 ~ 1 L L I L ~ I L T
6 I I I I I I ~~D rl rl~D 3 O I I C~~) R Q O ~ ~0 ~ C.~
I II I I I I O O O O O O ID C~ O
I X I I I I :r ~ c z z z z z z z z ~
Q
E OLn ~ O
X ~ ~I r-l ~Jr~l ~1 1~1r I~11--l r -l ~r ,.
~ ~ 54~
g ~ ~ o ~
. ~ ~ ~O
Q
. O I I ~1 1 0 1 ~ I r~) I I I I
:~ ~ t` ~ ~ ~ ~ > O
3 U~ U) 10 0 0 Il In ~ ~ a~ n ~ o o C)~
a~ ~ o o In In~1 $ O In o o ~ ~1 o n E ~ a Cll ~1 ~ In QD Cl) /:T~
I_ o ~1 O
O ~
a)z x _l L Q~I Q a~ o U~ a~ a) L L
E L ~ O O ~ O ~ C SJ ~ Il) ~ ~ ~
::S a) ~ L C C L ~ W 3 0 0 5 ~1 ~IISa.t~ Q~ Q3~
O ' ~1 0 ~ O:~`
Oi~ ~ x s ~ 1 n Xrl 0~3 Z N
:~ I
O U) 3~
c~ L o ,1 ~` --I N
I I ~ Q ~ O ~
I I C) L D rl 0 ~15 ~1 ~ I ~ I
Z Z ~t~ Z t~ O
I I Ia) I I I Q ~ N
O ~ C ) O O ~) I ~ C O ~ O
~ O .
I I I I I -r Z Z Z Z Z Z Z Z I Z Z Z
o ~1 ~ ~ ~In ~I~ a~ O~ o ~
X ~ ~I C~ 1 N
IIJ
~.~
. ~ :
,1 ~ Q G) ~GlID La~ ~ C o al C ~ C Q~
O ~JJ~JJJ Q ~
~D ~ L 0 ~ 0 ~ O ~ 0 C 11) ~~1 ~ S:t3 ~: ~ O ~ X ~ O~
O) E.1:1 E
.,1 >`
N ~I N
I ~ J ~ N O
I ~ rl ~ O I I --1~! I N I U~ I
Z IUl L O r Q Q >~ N I N
d ~ ~i9 3 d o ILn l~n ~ ~ Im ~ ILn ~ Im O O ~1 0 ~ 1 L L I L ~ I L T
6 I I I I I I ~~D rl rl~D 3 O I I C~~) R Q O ~ ~0 ~ C.~
I II I I I I O O O O O O ID C~ O
I X I I I I :r ~ c z z z z z z z z ~
Q
E OLn ~ O
X ~ ~I r-l ~Jr~l ~1 1~1r I~11--l r -l ~r ,.
~ ~ 54~
g ~ ~ o ~
. ~ ~ ~O
Q
. O I I ~1 1 0 1 ~ I r~) I I I I
:~ ~ t` ~ ~ ~ ~ > O
3 U~ U) 10 0 0 Il In ~ ~ a~ n ~ o o C)~
a~ ~ o o In In~1 $ O In o o ~ ~1 o n E ~ a Cll ~1 ~ In QD Cl) /:T~
I_ o ~1 O
O ~
a)z x _l L Q~I Q a~ o U~ a~ a) L L
E L ~ O O ~ O ~ C SJ ~ Il) ~ ~ ~
::S a) ~ L C C L ~ W 3 0 0 5 ~1 ~IISa.t~ Q~ Q3~
O ' ~1 0 ~ O:~`
Oi~ ~ x s ~ 1 n Xrl 0~3 Z N
:~ I
O U) 3~
c~ L o ,1 ~` --I N
I I ~ Q ~ O ~
I I C) L D rl 0 ~15 ~1 ~ I ~ I
Z Z ~t~ Z t~ O
I I Ia) I I I Q ~ N
O ~ C ) O O ~) I ~ C O ~ O
~ O .
I I I I I -r Z Z Z Z Z Z Z Z I Z Z Z
o ~1 ~ ~ ~In ~I~ a~ O~ o ~
X ~ ~I C~ 1 N
IIJ
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Claims (5)
1, A process for the preparation of 2-methylene--quinoxaline-1,4-dioxide derivatives of the general formula /I/
wherein A represents a hydroxyl or an amino group, or a group of the general formula -NH COOR1, wherein R1 denotes a C1-4 alkyl group, or a group of the general formula -NH-CX-NH2, wherein X
stands for oxygen or sulfur;
or a group of the formula -NH-C/=NH/-NH2;
or a group of the general formula -NH-R2, wherein R2 represents C1-6 alkyl, phenyl, benzyl, hydroxyl or hydroxy--/C2-4 alkyl/;
or a group of the general formula -NH-CO-R3, wherein R3 stands for a C1-20 alkyl group, a phenyl group optionally substituted by one, two or three identical or different substituent/s/ selected from the group consisting of hydroxyl, amino, nitro, C1-4 alkyl, C1-4 alkoxy or halogen;
a piperidyl, a pyridyl, a furyl, a nitrofuryl, a pyrazinyl, a pyrimidyl, a naphthyl, a hydroxynaphthyl, a phenylalkyl, an 1,2,4-triazinyl, an .alpha.,.alpha.-diphenyl-.alpha.--hydroxymethyl, a cyanomethyl, a halomethyl or a hydroxymethyl group, characterized by dehydrating a compound of the general formula /II/
wherein A has the same meanings as above.
wherein A represents a hydroxyl or an amino group, or a group of the general formula -NH COOR1, wherein R1 denotes a C1-4 alkyl group, or a group of the general formula -NH-CX-NH2, wherein X
stands for oxygen or sulfur;
or a group of the formula -NH-C/=NH/-NH2;
or a group of the general formula -NH-R2, wherein R2 represents C1-6 alkyl, phenyl, benzyl, hydroxyl or hydroxy--/C2-4 alkyl/;
or a group of the general formula -NH-CO-R3, wherein R3 stands for a C1-20 alkyl group, a phenyl group optionally substituted by one, two or three identical or different substituent/s/ selected from the group consisting of hydroxyl, amino, nitro, C1-4 alkyl, C1-4 alkoxy or halogen;
a piperidyl, a pyridyl, a furyl, a nitrofuryl, a pyrazinyl, a pyrimidyl, a naphthyl, a hydroxynaphthyl, a phenylalkyl, an 1,2,4-triazinyl, an .alpha.,.alpha.-diphenyl-.alpha.--hydroxymethyl, a cyanomethyl, a halomethyl or a hydroxymethyl group, characterized by dehydrating a compound of the general formula /II/
wherein A has the same meanings as above.
2. A process as claimed in claim 1, characterized by carrying out the reaction in an indifferent solvent, at the boiling point thereof.
3. A process as claimed in claim 2, characterized by using water, aliphatic alcohols or aromatic hydrocarbons as indifferent solvent.
4. A process as claimed in claim 1, characterized by carrying out the reaction in the presence of a dehydrating agent,
5. A process as claimed in claim 4, characterized by using polyphosphoric acid, sulfuric acid or calcium chloride as dehydrating agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU2240/80 | 1980-09-12 | ||
| HU224080 | 1980-09-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1154770A true CA1154770A (en) | 1983-10-04 |
Family
ID=10958457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000385733A Expired CA1154770A (en) | 1980-09-12 | 1981-09-11 | Process for the preparation of 2-methylene- quinoxaline-1,4-dioxide derivatives |
Country Status (14)
| Country | Link |
|---|---|
| AR (1) | AR226749A1 (en) |
| BE (1) | BE890300A (en) |
| CA (1) | CA1154770A (en) |
| DE (1) | DE3136092A1 (en) |
| DK (1) | DK405181A (en) |
| ES (1) | ES8206492A1 (en) |
| FI (1) | FI812835L (en) |
| FR (1) | FR2490226A1 (en) |
| GB (1) | GB2083817A (en) |
| IL (1) | IL63803A0 (en) |
| IT (1) | IT1139962B (en) |
| PT (1) | PT73655B (en) |
| SE (1) | SE8105427L (en) |
| YU (1) | YU218781A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617493B (en) * | 2012-02-22 | 2014-06-04 | 中国农业大学 | Mequindox artificial antigens and antibodies prepared by same |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1469485A (en) * | 1964-09-16 | 1967-02-17 | Pfizer & Co C | Process for the preparation of a new series of schiff bases |
| US3493572A (en) * | 1968-07-05 | 1970-02-03 | Pfizer & Co C | Process for producing quinoxaline-di-n-oxides |
| US3926992A (en) * | 1972-11-03 | 1975-12-16 | Pfizer | Aldol products of 2-quinoxalinecarboxaldehy-1,4-dioxides |
| US4221791A (en) * | 1979-05-21 | 1980-09-09 | International Minerals & Chemical Corp. | Substituted quinoxaline dioxides |
-
1981
- 1981-09-10 BE BE1/10310A patent/BE890300A/en not_active IP Right Cessation
- 1981-09-11 IT IT23898/81A patent/IT1139962B/en active
- 1981-09-11 PT PT73655A patent/PT73655B/en unknown
- 1981-09-11 GB GB8127507A patent/GB2083817A/en not_active Withdrawn
- 1981-09-11 AR AR286743A patent/AR226749A1/en active
- 1981-09-11 FI FI812835A patent/FI812835L/en not_active Application Discontinuation
- 1981-09-11 FR FR8117209A patent/FR2490226A1/en active Pending
- 1981-09-11 CA CA000385733A patent/CA1154770A/en not_active Expired
- 1981-09-11 DE DE19813136092 patent/DE3136092A1/en not_active Withdrawn
- 1981-09-11 SE SE8105427A patent/SE8105427L/en not_active Application Discontinuation
- 1981-09-11 DK DK405181A patent/DK405181A/en not_active Application Discontinuation
- 1981-09-11 IL IL63803A patent/IL63803A0/en unknown
- 1981-09-11 YU YU02187/81A patent/YU218781A/en unknown
- 1981-09-12 ES ES505442A patent/ES8206492A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| IT8123898A0 (en) | 1981-09-11 |
| DE3136092A1 (en) | 1982-05-27 |
| IT1139962B (en) | 1986-09-24 |
| BE890300A (en) | 1982-03-10 |
| AR226749A1 (en) | 1982-08-13 |
| GB2083817A (en) | 1982-03-31 |
| FR2490226A1 (en) | 1982-03-19 |
| IL63803A0 (en) | 1981-12-31 |
| YU218781A (en) | 1983-04-30 |
| SE8105427L (en) | 1982-03-13 |
| ES505442A0 (en) | 1982-08-16 |
| PT73655A (en) | 1981-10-01 |
| FI812835L (en) | 1982-03-13 |
| PT73655B (en) | 1982-11-22 |
| ES8206492A1 (en) | 1982-08-16 |
| DK405181A (en) | 1982-03-13 |
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| MKEX | Expiry |