Condensation reagents and a process for their preparation
View Patent ↗The present invention relates to new bromo- and chlorothiazolium salts of the formula (I) in which R 1 , R 2 , R 3 , R 4 , n and X − have the meaning indicated in the disclosure, a process for their preparation, their use as condensation reagents, particularly as peptide coupling reagents, and intermediates for the preparation of these compounds.
1. A compound of the formula (I)
in which
R 1 represents methyl, ethyl, n-propyl, isopropyl, hydroxyl, methylsulfonyl, ethylsulfonyl, phenylsulfonyl, p-methylphenylsulfonyl, or benzyl that is optionally substituted by halogen, nitro, C 1 -C 4 -alkyl, trifluoromethyl, or C 1 -C 4 -alkoxy,
R 2 and R 3 together represent —(CH 2 ) n — that is optionally substituted by halogen, NO 2 , carboxyl, carbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, or C 1 -C 4 -halogenoalkoxy or the optionally halogen-, NO 2 —, C 1 -C 4 -alkyl-, C 1 -C 4 -halogenoalkyl-, C 1 -C 4 -alkoxy-, or C 1 -C 4 -halogenoalkoxy-substituted groups having the formulas
where the arrows mark the points of linkage to the thiazole ring, and n represents 3, 4 or 5,
R 4 represents bromine or chlorine, and
X − represents chloride, bromide, iodide, hydrogen sulfate, ½ equivalent of sulfate, sulfate, hexachloroantimonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, tetrafluoroborate, tetraphenylborate, or hexafluorophosphate.
2. A compound of the formula (I) according to claim 1 , wherein
R 1 represents methyl, ethyl, n-propyl, hydroxyl, methylsulfonyl, ethylsulfonyl, or benzyl that is optionally substituted by fluorine and/or chlorine, methyl, ethyl, n- or i-propyl, trifluoromethyl, methoxy, ethoxy, or n- or i-propoxy,
R 2 and R 3 together represent —(CH 2 ) n — substituted by fluorine and/or chlorine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, or carbonyl or the groups having the formulas
and n represents 3 or 4,
R 4 represents bromine, and
X − represents bromide, ½ equivalent of sulfate, sulfate, SbCl 6 − , mesylate, triflate, tosylate, tetrafluoroborate, tetraphenylborate, or hexafluorophosphate.
3. A compound of the formula (I) according to claim 1 , wherein
R 1 represents methyl, ethyl, methylsulfonyl, ethylsulfonyl, or benzyl that is optionally substituted by fluorine and/or chlorine,
R 2 and R 3 together represent —(CH 2 ) n — that is optionally substituted by fluorine and/or chlorine, methyl, ethyl, or carbonyl, and
X − represents bromide, ½ equivalent of sulfate, sulfate, or tetrafluoroborate.
4. A compound of the formula (I) according to claim 1 , wherein
R 4 represents bromine.
5. A compound of the formula (I-2)
in which
R 1 represents methyl, ethyl, n-propyl, isopropyl, hydroxyl, methylsulfonyl, ethylsulfonyl, phenylsulfonyl, p-methylphenylsulfonyl, or benzyl that is optionally substituted by halogen, nitro, C 1 -C 4 -alkyl, or C 1 -C 4 -alkoxy,
R 2 and R 3 together represent —(CH 2 ) n — that is optionally substituted by halogen, NO 2 , carboxyl, carbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, or C 1 -C 4 -halogenoalkoxy or the optionally halogen-, NO 2 —, C 1 -C 4 -alkyl-, C 1 -C 4 -halogenoalkyl-, C 1 -C 4 -alkoxy-, or C 1 -C 4 -halogenoalkoxy-substituted groups having the formulas
where the arrows mark the points of linkage to the thiazole ring, and n represents 3, 4 or 5,
R 4 represents bromine or chlorine, and
X″ − represents tetrafluoroborate, tetraphenylborate, or hexafluorophosphate.