Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
1999-09-21
2001-02-27
Shah, Mukund J. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
C544S215000, C544S216000, C544S224000, C544S238000, C544S240000, C544S241000, C544S309000, C544S315000, C544S319000, C544S336000, C544S355000, C544S405000, C546S266000, C546S290000, C546S332000, C548S146000, C548S186000, C548S205000, C548S206000, C548S213000, C548S225000, C548S226000, C548S240000, C548S243000, C549S272000
Reexamination Certificate
active
06194575
ABSTRACT:
The present invention relates to a novel type of process for the preparation of 1,3-disubstituted 2-nitroguanidines.
EP-A-0 483 062 discloses a process for the preparation of 1,3-disubstituted 2-nitroguanidines. They are obtained by hydrolysis of corresponding 2-nitroimino-1,3,5-triazacyclohexane derivatives. The hydrolysis is preferably carried out in the presence of strong mineral acids or organic acids.
Disadvantages of this process are the long reaction times and the formation of secondary products, which make it necessary to subject the desired end-products to a complex cleaning operation.
Moreover, as is known, when working in the presence of strong acids, measures must be taken to protect, for example the reactors, from corrosion.
JP-03 291 267 relates to a similar process.
The object of the present invention was to provide a further process for the preparation of 1,3-disubstituted 2-nitroguanidines.
The present invention provides a process for the preparation of compounds of the formula (I)
in which
R
1
is hydrogen or C
1
-C
4
-alkyl,
R
2
is hydrogen, C
1
-C
6
-alkyl, C
3
-C
6
-cycloalkyl or a radical —CH
2
R
3
,
R
3
is C
2
-C
5
-alkenyl, C
2
-C
5
-alkinyl, phenyl, cyanophenyl, nitrophenyl, halogenophenyl having from 1 to 3 halogen atoms, phenyl substituted by C
1
-C
3
-alkyl, C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, C
1
-C
3
-alkoxy or C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, 3-pyridyl, 5-thiazolyl, 5-thiazolyl substituted by one to two (preferably one) substituents from the group consisting of C
1
-C
3
-alkyl, C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl having from 1 to 3 halogen atoms, C
2
-C
3
-alkenyl, C
2
-C
3
-alkinyl, C
1
-C
3
-alkoxy, C
2
-C
3
-halogenoalkenyl and C
2
-C
3
-halogenoalkinyl having in each case from 1 to 4 halogen atoms, C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, C
1
-C
3
-alkylthio, C
1
-C
3
-halogenoalkylthio having from 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargylthio, halogenoallyloxy and halogenoallylthio having in each case from 1 to 3 halogen atoms, halogen, cyano and nitro; or 3-pyridyl substituted by one to four (preferably one or two) radicals from the group consisting of C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl having from 1 to 3 halogen atoms, C
2
-C
3
-alkenyl, C
2
-C
3
-alkinyl, C
2
-C
3
-halogenoalkenyl and C
2
-C
3
-halogenoalkinyl having in each case from 1 to 4 halogen atoms, C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, C
1
-C
3
-alkylthio, C
1
-C
3
-halogenoalkylthio having from 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargylthio, halogenoallyloxy and halogenoallylthio having in each case from 1 to 3 halogen atoms, cyano, nitro, C
1
-C
3
-alkyl, C
1
-C
3
-alkoxy and halogen,
Het is an unsubstituted or substituted aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical, preferably from the series
which may include one or two substituents from the group consisting of C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl having from 1 to 3 halogen atoms, C
2
-C
3
-alkenyl, C
2
-C
3
-alkinyl, C
2
-C
3
-halogenoalkenyl and C
2
-C
3
-halogenoalkinyl having in each case from 1 to 4 halogen atoms, C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, C
1
-C
3
-alkylthio, C
1
-C
3
-halogenoalkylthio having from 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargylthio, halogenoallyloxy and halogenoallylthio having in each case from 1 to 3 halogen atoms, cyano, nitro, C
1
-C
3
-alkyl, C
1
-C
3
-alkoxy and halogen,
characterized in that a compound of the formula (II)
in which
R
1
, R
2
and Het are as defined above, and
R
4
is C
1
-C
10
-alkyl, C
3
-C
6
-cycloalkyl, phenyl, benzyl or heterocyclylmethyl, each of which may be unsubstituted or substituted, where heterocyclyl is an unsaturated or saturated 5- or 6-membered heterocycle containing one or two (preferably one) heteroatoms from the series nitrogen, oxygen and sulphur, such as, for example, furan, tetrahydrofuran, thiophene or pyridine, is reacted with urea in the presence of a diluent.
The compounds of the formula (I) can also be in the form of double-bond isomers as regards the —N═C(2) bond and in their tautomeric forms (formulae Ia, Ib):
Formula (I) is accordingly to be taken to mean that it also includes the corresponding double-bond isomers and the formulae (Ia) and (Ib).
Surprisingly, the process according to the invention produces, selectively and in high yields, the end-products of the formula (I) in pure form after a short reaction time under mild reaction conditions.
For example, using1-(2-chlorothiazol-5-ylmethyl)-2-nitro-imino-3,5-dimethyl-1,3,5-triazacyclohexane as starting material, the course of the process according to the invention can be shown by the following equation:
The compounds required as starting materials for the process according to the invention are generally defined by the formula (II).
Preferred substituents and ranges of the radicals listed in the formulae mentioned above and below are illustrated below:
R
1
is preferably hydrogen, methyl, ethyl, n- or i-propyl,
R
2
is preferably hydrogen, methyl, ethyl, n-propyl, i-propyl or n-butyl, cyclopropyl, cyclopentyl, cyclohexyl or a radical—CH
2
R
3
,
R
3
is preferably C
2
-C
5
-alkenyl, C
2
-C
5
-alkinyl, phenyl, cyanophenyl, nitrophenyl, halogenophenyl having from 1 to 3 halogen atoms, phenyl substituted by C
1
-C
3
-alkyl, C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, C
1
-C
3
-alkoxy or C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, 3-pyridyl, 5-thiazolyl, 5-thiazolyl substituted by one to two (preferably one) substituents from the group consisting of C
1
-C
3
-alkyl, C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, cyclopropyl, halogeno-cyclopropyl having from 1 to 3 halogen atoms, C
2
-C
3
-alkenyl, C
2
-C
3
-alkinyl, C
1
-C
3
-alkoxy, C
2
-C
3
-halogenoalkenyl and C
2
-C
3
-halogenoalkinyl having in each case from 1 to 4 halogen atoms, C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, C
1
-C
3
-alkylthio, C
1
-C
3
-halogenoalkylthio having from 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargylthio, halo-genoallyloxy and halogenoallylthio having in each case from 1 to 3 halogen atoms, halogen, cyano and nitro; or 3-pyridyl substituted by one to two (preferably one) radicals from the group consisting of C
1
-C
3
-halogenoalkyl having from 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl having from 1 to 3 halogen atoms, C
2
-C
3
-alkenyl, C
2
-C
3
-alkinyl, C
2
-C
3
-halogenoalkenyl and C
2
-C
3
-halogenoalkinyl having in each case from 1 to 4 halogen atoms, C
1
-C
3
-halogenoalkoxy having from 1 to 7 halogen atoms, C
1
-C
3
-alkylthio, C
1
-C
3
-halogenoalkylthio having from 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargylthio, halogenoallyloxy and halogenoallylthio having in each case from 1 to 3 halogen atoms, cyano, nitro, C
1
-C
3
-alkyl, C
1
-C
3
-alkoxy and halogen,
R
4
is preferably C
1
-C
10
-alkyl, C
3
-C
6
-cycloalkyl, C
1
-C
10
-alkyl substituted by from 1 to 12 radicals from the group consisting of halogen, hydroxyl, C
1
-C
4
-alkoxy, C
1
-C
4
-halogenoalkoxy having from 1 to 9 halogen atoms, di-(C
1
-C
4
-alkyl)-amino and C
1
-C
5
-alkoxycarbonyl, C
3
-C
6
-cycloalkyl substituted by from 1 to 4 radicals from the series C
1
-C
4
-alkyl and halogen, phenyl, benzyl, or phenyl or benzyl in each case substituted by from 1 to 3 ring substituents from the group consisting of halogen, C
1
-C
4
-alkyl, C
1
-C
4
-halogenoalkyl having from 1 to 9 halogen atoms, C
1
-C
4
-alkoxy, C
1
-C
4
-halogenoalkoxy having from 1 to 9 halogen atoms, C
1
-C
4
-alkylthio, nitro and cyano, or heterocyclylmethyl where heterocyclyl is an unsaturated or saturated 5- or 6-membered heterocycle having one or two (preferably one) heteroatoms from the series nitrogen, oxygen and sulphur, such as, for example, furan, tetrahydrofuran, thiophene or pyridine,
Kramer Wolfgang
Rivadeneira Eric
Wollweber Detlef
Balasubramanian Venkataraman
Bayer Aktiengesellschaft
Gil Joseph C.
Shah Mukund J.
LandOfFree
Method for producing 1,3-di-substituted 2-nitroguanidines does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for producing 1,3-di-substituted 2-nitroguanidines, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for producing 1,3-di-substituted 2-nitroguanidines will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2606988