3-Isothiazolones

Table 13 shows some of the developmental products that have EPA appHcations pending and may be available in the near future. Sea Nine is a variation on the very successflil isothiazolone chemistry. It is claimed to be an improvement over metallic actives used for antifouling paint and wood preservation (46,47). Decylthioethylamine and its water-soluble hydrochloride are claimed to be especially effective at controlling biofilm in cooling water appHcations (48—50). The hydroxymethylpyra2ole shown is also suggested to have properties that are well suited to the protection of aqueous products or emulsions (51,52). 

Many analogues of saccharin have been synthesized since its discovery. With the exception of one compound, thieno[3,4-i/ isothiazolone dioxide [59337-79-0] lOOOX, this effort has not generated more potent compounds. Acesulfame-K could be considered a ring-modification derivative of saccharin, however. 

Malachite green (0.0...2.0) uracil derivatives, triazine herbicides [163] polar lipids [246, 247] phospholipids [248, 249] fatty acids, fatty aldehydes, phospholipids and glycolipids [250] microbiocidal isothiazolones [251]... 

The formation of methyl(benzylsulfonyl)oxamate 70 as the reactive intermediate in the reaction of arylmethanesulfamide 69 and diethyl oxalate, giving 5-aryl-4-hydroxy-3(2f/)-isothiazolone 71, has been reported (99MI1). 

Isothiazolone dioxide rings are readily cleaved in diluted aqueous alkaline solution at r.t. and this feature allows their use, in some cases, as a protecting group (95TL(36)6227). An example is the efficient Fischer indole synthesis of 72. 

Isonicotinic acid hydrazide reagent 318 Isoprenaiine 395,396 Isoprenoid compounds 44 Isopulegol 59 Isoquercitrin 279, 280, 323 Isoquinoline alkaloids 46, 66, 262 Isorhamnetin 323 Isothiazolones, microbiocidal 45 Isothiocyanates 75 Isotopes, j8-radiation-emitting 41 -, detection limits 41 Itaconic acid 61... 

Isoihamnetin la 323 Isothiazolone, microbiocidal la 45 Isothiocyanates la 75 lb 312 Isothiocyanate anions lb 307 Isotopes, detection limits la 41 Itaconic acid, reduction la 61 lodazide reaction lb 301,303... 

Collier P.J., Ramsey A.J., Austin P. Gilbert P. (1991) Uptake and distribution of some isothiazolone... 

A. B. Downey, G. L. Willingham, and V. S. Frazier. Compositions comprising 4,5-dichloro-2-N-octyl-3-isothiazolone and certain commercial biocides. Patent EP 680695, 1995. 

J. C. Hsu. Synergistic microbicidal combinations containing 3-isothiazolone and commercial biocides. Patent US 4906651, 1990. 

Although these are all used across Europe, the hierarchy of these has altered slightly due to the influences of environmental legislation. For example, Chloro-isothiazolone has been identified as a skin sensitiser and hence therefore lost its number one position as a controlling agent. New actives such as the Octyl - isothiazolone have recently been introduced as a more stable molecule where it is hoped that lower levels can be used reducing environmental and human safety aspects. 

While starches are commonly used, they are relatively poor viscosifiers. Acids and bacterial enzymes readily attack the acetal linkages resulting in facile depolymerization. Both formaldehyde and isothiazolones have been used as starch biocides (17). Development of improved high temperature water viscosifiers for drilling and other oil field applications is underway. For the... 

The formation of l,3,4-triarylpyrroline-2,5-diones from the reaction of diphenylcyclopropenone and N-sulfinylarylamines with nickel carbonyl has been described earlier (see Scheme 36 in Section IV,A,2).64 In contrast with this result, 2,4,5-triphenyl-3-isothiazolone 1-oxide is produced in this type of process using iron pentacarbonyl, and the analogous cyclohexyl derivative is formed in a nickel carbonyl-mediated reaction (Scheme 115).64 It is probable that metallocyclic species (cf. 93) are intermediates in these transformations. 

Single coordination units are found where the O ligands are large, as in Ph3SnLL 144 for L = diphenylcyclopropenone and L an isothiazolone or the similar saccharine. OSnO is near-linear and CSnC adjust to steric factors in the range 114-134°, SnO(ketone) = 237-241 pm, Sn-O(hetero-ring) = 216 pm, Sn-C = 211-216 pm. 

Isothermal transformation (IT) diagrams, 17 16 23 277-280 for eutectoid steel, 23 279 Isothiazolone marine antifoulant,... 

Figure 11.3 Anacardic acid analog 7, y-butyrolactone MB-3 8, isothiazolones CCT077791 9 and CCT077792 10 and the quinolines n, 12 and 13.

Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P. et al. (2005) Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Molecular Cancer Therapeutics, 4, 1521—1532. 

A number of examples of the transformation of other heterocycles into 1,2,3-thiadiazoles were collected in the first edition <84CHEC-i(6)447>. Few other examples have since appeared one interesting case is the reaction of isothiazolone (41) with hydrazine to form a 1,2,3-thiadiazole (Equation (20)) <84JHC1679>. 

Thus far, at least one class of compound — isothiazolone derivatives — has been identified as potent IL-5 inhibitors. These substances react with a free sulphydryl group on the surface of the IL-5 receptor a-subunit, thereby preventing ligand binding. Isothiazolones are already used as anti-microbial agents, but are quite toxic. 

An indolone comprises a prominent moiety in the dopamine D2 selective antipsychotic agent ziprasidone (32-8). Reduction of the ketonoid carbonyl group on the indoxyl (32-1) under Wolff-Kischner conditions affords the indolone (32-2). Acylation of the product with chloroacetyl chloride in the presence of aluminum chloride then affords the reactive chloroacetyl derivative (32-3). In a convergent sequence, reaction of isothiazolone (32-4) with phosphorus oxychloride leads to... 

Substituted 3(2//)-isothiazolones 54 were obtained from furanones 41, which are easily prepared from 3-aroylpropionic acids (83JHC1545), by the sequence shown in Scheme 17 (87H569). 

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