Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2001-05-04
2003-06-10
Kumar, Shailendra (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S134000, C564S189000, C564S190000
Reexamination Certificate
active
06576792
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to new chemical compounds belonging to the class of 2-halo-1-cycloalkenecarboxamides. It further relates to the preparation and the use of the compounds as intermediates in the production of a class of compounds useful as industrial biocides.
BACKGROUND OF THE INVENTION
4,5-Tri- and tetramethylene-4-isothiazolin-3-ones are a class of compounds known to have useful antimicrobial activity and several compounds of this type are commercially available and are used as industrial biocides. The preparation and use of such biocides have been described in the prior art, for example, in U.S. Pat. Nos. 4,708,959; 4,851,541; 5,082,966; 5,315,009; 5,336,777; and 5,466,814.
All of the preparations that have been disclosed in the prior art use either a mercapto intermediate which requires the use of hydrogen sulfide as a raw material in the preparation of the intermediate, or a sulfoxide (or sulfphinyl) intermediate which requires the use of benzyl mercaptan as a raw material in the preparation of the intermediate. Hydrogen sulfide, a colorless gas, and benzyl mercaptan, a colorless to pale yellow liquid, both have an obnoxious odor and require special equipment and handling in order to meet a “no-leak” and “no-spill” condition. It is, therefore, desirable to develop a new intermediate that does not require such an odorous gas or liquid raw material.
SUMMARY OF THE INVENTION
This invention provides novel 2-halo-1-cycloalkenecarboxamides represented by general Formula I:
wherein
n is 1 or 2;
R is hydrogen or a substituted or unsubstituted alkyl group; and
X is a halogen.
In another aspect this invention provides a method of making a 2-halo-1-cycloalkenecarboxamide compound represented by Formula I, the method comprising:
(a) reacting a 2-oxo-1-cycloakylcarboxyester represented by Formula II;
wherein
n is 1, or 2;
R′ is methyl, or ethyl; with a halogenating agent to produce a mixture of 2-halo-1-cycloalkenecarboxyacid halide and 2-halo-1-cycloalkenecarboxyester, and
(b) subsequently reacting the mixture with ammonia or an alkylamine having the formula;
R—NH
2
wherein R is a substituted or unsubstituted alkyl group as defined for the R of the Formula I.
ADVANTAGEOUS EFFECT OF THE INVENTION
The present invention provides 2-halo-1-cycloalkenecarboxamides as intermediates for the preparation of 4,5-tri- and tetramethylene-4-isothiazolin-3-one biocides. Such intermediates can be converted to biocide precursors using an odorless solid raw material such as an ammonium or alkali-metal salt of hydrosulfide or thiocyanate. This provides for a safer and more efficient manufacturing process as it avoids spillage and gas leakage. There is also a reduced need for odor control.
DETAILED DESCRIPTION OF THE INVENTION
The compounds of the present invention are 2-halo-1-cycloalkenecarboxamides represented by Formula I;
In the above formula R can be any substituent that does not adversely affect the biocide activity or unduly interfere with the manufacture of the 4,5-tri- or tetramethylene-4-isothiazoline-3-one compounds. Preferably, R is hydrogen, or a substituted or unsubstituted alkyl group, such as an alkyl group containing 1 to 16, and more typically 1 to 12 carbon atoms. The alkyl group may be cyclic or branched. Examples of suitable alkyl groups include methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl groups etc. Representative substituted alkyl groups include arylalkyl groups, heteroarylalkyl groups, or alkyl groups substituted with halogens, alkoxy or alkoxycarbonyl groups. Examples of suitable branched alkyl groups are isopropyl, 2-methylpropyl, sec-butyl, 3-methylbutyl, 3-methyl-2-butyl, 4-methyl-3-buten-2-yl, 2-pentyl, 3-pentyl, 2-hexyl and 3-hexyl groups. Examples of suitable cyclic alkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and 4-methylcyclohexy groups. Examples of suitable arylalkyl groups are alkyl groups substituted with benzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, 4-ethoxycarbonylbenzyl, 4-methoxycarbonyl-benzyl and 4-cyanobenzyl groups. Examples of suitable heteroarylalkyl groups are 2-furylmethyl, 2-pyrrolemethyl, 2-pyridylmethyl, and 2-thienylmethyl groups. Examples of suitable alkyl groups substituted with halogens, alkoxy or alkoxycarbonyl groups are 2-chloroethyl, 2-bromoethyl, 3-chloropropyl, 4-chlorobutyl, methoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl and 2-ethoxycarbonylethyl groups.
n is 1 or 2. X is a halogen such as fluorine, chlorine, bromine, or iodine. Preferred halogens are chlorine and bromine.
When reference in this application is made to a particular group, unless otherwise specifically stated, the group may itself be unsubstituted or substituted with one or more substituents (up to the maximum possible number). For example, “alkyl” group refers to a substituted or unsubstituted alkyl group, while “benzene” refers to a substituted or unsubstituted benzene (with up to six substituents). The substituent may be itself substituted or unsubstituted. The particular substituents used may be selected by those skilled in the art to attain the desired biocidal properties for a specific application and can include, for example, hydrophobic groups, solubilizing groups, blocking groups, and releasing or releasable groups. When a molecule may have two or more substituents, the substituents may be joined together to form a ring such as a fused ring unless otherwise provided.
Generally, unless otherwise specifically stated, substituents include any substituents, whether substituted or unsubstituted, which do not destroy properties necessary for the biocidal utility. Examples of substituents include known substituents, such as: halogen, for example, chloro, fluoro, bromo, iodo; alkoxy, particularly those “lower alkyl” (that is, with 1 to 6 carbon atoms, for example, methoxy, ethoxy; substituted or unsubstituted alkyl, particularly lower alkyl (for example, methyl, trifluoromethyl); thioalkyl (for example, methylthio or ethylthio), particularly either of those with 1 to 6 carbon atoms; substituted and unsubstituted aryl, particularly those having from 6 to 20 carbon atoms (for example, phenyl); and substituted or unsubstituted heteroaryl, particularly those having a 5- or 6-membered ring containing 1 to 3 heteroatoms selected from N, O, or S (for example, pyridyl, thienyl, furyl, pyrrolyl); acid or acid salt groups such as any of those described below; and others known in the art. Alkyl substituents may specifically include “lower alkyl” (that is, having 1-6 carbon atoms), for example, methyl, ethyl, and the like. Further, with regard to any alkyl group or alkylene group, it will be understood that these can be branched or unbranched and include ring structures.
In another aspect the invention relates to a method of making the 2-halo-1-cycloalkenecarboxamide intermediates from 2-oxo-1-cycloalkylcarboxyesters (Formula II). Such cycloalkylcarboxyesters are readily available either by carboxylation and esterification of cycloalkylketone such as cyclopentanone or cyclohexanone, or self-condensation of dibasic esters such as dimethyl adipate or diethyl adipate.
The method of making the intermediates comprises a two-step non-isolation process as shown in the Scheme I below. The first step is reacting a 2-oxo-1-cycloakylcarboxyester represented by Formula II with a halogenating to produce a mixture of 2-halo-1-cycloalkenecarboxyacid halide and 2-halo-1-cycloalkenecarboxyester. The second step is subsequently reacting the mixture with ammonia or an alkylamine (R—NH
2
) as defined below.
wherein
n is 1 or 2;
R′ is methyl or ethyl;
X is a halogen;
R is hydrogen or an alkyl group as defined above.
The first step reaction requires an excess amount of a strong halogenating agent in order to produce a mixture of 2-oxo-1-cycloalkylcarboxyacid halide and 2-oxo-1-cycloalkenecarboxy esters. A 2-halo-1-cycloalkenecarboxyacid halide is highly reactive and readily reacts with any alkylamine to form the desired intermediate, but a 2-halo-1-cycloalk
Kumar Shailendra
Meeks Roberts Sarah
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