Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-08-09
1997-01-14
McKane, Joseph K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548209, 106 1833, 528935, 804269, C09D 516, A01N 4380, C07D27504
Patent
active
055940188
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/00320 filed Feb. 17, 1994.
The present invention relates to N-(.beta.-branched alkyl)-1,2-benziso-thiolin-3-ones, and to their preparation and their use as industrial biocides.
N-alkyl-1,2-benzisothiazolin-3-ones (hereinafter referred to as N-alkyl-BIT) constitute an important group of industrial biocides which are particularly effective in inhibiting the growth of bacteria and fungi. Compounds of this type, their preparation and use are disclosed in GB 848,130 where the N-alkyl group contains at least 4 carbon atoms, including .alpha.- branched alkyl groups such as tertiary butyl. DE 4027378 discloses N-(linear C.sub.6-8 -alkyl)- BIT which are particularly effective against fungi. U.S. Pat. No. 3,761,488 discloses N-alkyl isothiazolinones but the only disclosed N- (.beta.-branched alkyl)isothiazolonones were reported to have inferior micro-biological activity compared with their linear alkyl analogues. Whereas the known N-alkyl-BIT's are reported to be effective against a broad spectrum of micro-organisms, industry is constantly seeking more active and cost-effective compounds. A new class of N-alkyl-BIT's has now been found with increased activity against micro-organisms, especially fungi. This is particularly surprising in the light of the reported results in U.S. Pat. No. 3,761,488.
According to the invention there is provided a compound of formula (I) ##STR1## and salts thereof wherein atoms; complete a ring; nitrile, hydroxy, carboxy or alkoxy carbonyl; and
The total number of carbon atoms represented by R, R.sup.1 and R.sup.2 (when not hydrogen) is preferably less than 18, more preferably less than 12 and especially less than 10.
When the phenyl ring of formula I is substituted, n is preferably 1 and X is preferably located in the 6-position of the BIT ring structure. It is, however, especially preferred that the phenyl ring is unsubstituted, i.e. n is preferably 0.
When R, R.sup.1 or R.sup.2 is substituted alkyl, the substituent is phenyl cyclohexyl, halogen, nitro, nitrile, hydroxy, carboxy, alkoxycarbonyl, acyloxy or C.sub.1-4 -lower alkoxy. It is preferred, however, that R, R.sup.1 and R.sup.2 are unsubstituted, and it is especially preferred that R.sup.2 is hydrogen. Preferably R.sup.1 is C.sub.2-4 -alkyl and R is preferably C.sub.2-10 -alkyl and especially C.sub.2-8 -alkyl.
When R and R.sup.1 together with the carbon atom to which they are attached complete a ring the ring is preferably alicyclic and is preferably a 3-, 5- or especially a 6-membered ring. In such compounds, R.sup.2 is preferably hydrogen. An especially preferred ring is cyclohexyl.
When X is halogen, it is preferably fluorine, or bromine and especially chlorine.
Whilst the compound of formula I is shown in the free amine form, it is also active in the form of a salt with an acid. The acid may be inorganic or organic. Examples of such acids are hydrochloric, sulphuric, citric and tartaric acids.
N-(2-ethylhexyl)-BIT and N-(2-ethylbutyl)-BIT have been found especially useful.
The compounds of formula I may be prepared by known methods for preparing N-substituted BIT's. formula II ##STR2## wherein X and n are as hereinbefore defined and Hal is Halogen, especially chlorine with an amine of formula (III) ##STR3## in an appropriate inert solvent wherein. R, R.sup.1 and R.sup.2 are as hereinbefore defined. The preparation of 2-chlorosulphenylbenzoyl chloride is described in "Synthetic Communications, 1983, 13 (12), 977 and its reaction with amines. formula IV ##STR4## in an inert organic solvent with an acid halide wherein R.sup.4 is the group ##STR5## R.sup.5 is C.sub.1-16 -alky, aryl or aralkyl; and R, R.sup.1, R.sup.2, X and n are as hereinbefore defined.
Preferably R.sup.5 is benzyl and the acid halide is preferably thionyl chloride, phosgene or proponyl chloride. Processes of this type are described in J.C.S. Chem. Comm. 1981, 510 and EP 419075. (V) ##STR6## with an alkyl halide, especially an alkyl bromide of formula VI ##STR7## in an appropriate inert solvent wherein R, R.sup.1,R.sup.2, X
REFERENCES:
patent: 3761488 (1973-09-01), Lewis et al.
Chemical Abstracts, vol. 68, No. 25, Jun. 17, 1968, abstract No. 114493,.
Ponci, R. et al: "Bis(2-carboxyphenyl) disulfide diamides and benzisothiazolinones. Influence of butyl groups on antifungal activity", Farmaco Ed. Sci., 22(12), 1967, 999-1010.
Baggaley et al., J. Med. Chem., 1985, 28, 1661-67 1985.
Ricci, et al., Phytochemistry, 29(9), 2787-91 1990.
Ambrosoli, et al., Boll. Chim. Farm., 109, 251-58 1970.
Massimo, et al., II Farmaco, 45(4), 439-46 1990.
Zani, et al., II Farmaco, 46(5), 639-46 1991.
Vitali et al., II Farmaco Ed. Sc., 23(11), 1075-80 1968.
Vitali et al., II Farmaco Ed. Sc., 23(5), 468-76 1968.
Kamigata, et al., Org. Prep. Proc. Int., 15(5), 315-19 1983.
Uchida, et al., Bull. Chem. Soc. Jpn., 55, 1183-87 1982.
Ponci et al., II Farmaco Ed. Sc., XXII(12), 999-1010 1967.
Krische et al., Chem. Ber., 116, 1708-27 1983.
Cross Laura R.
McKane Joseph K.
Zeneca Limited
LandOfFree
2-(B-branched alkyl)-benziosothiazolin-3-ones does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 2-(B-branched alkyl)-benziosothiazolin-3-ones, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 2-(B-branched alkyl)-benziosothiazolin-3-ones will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1388554