Thiazolines ring-opening

Potassium tert-butoxide Z 2-Thiazoline ring opening with subsequent transesterification of thioiminoesters... 

A -Thiazoline-4-carboxylic acids, metalation 26, 644s32 A -Thiazoline ring opening... 

Synthesis of cysteinylpeptides via thiazolidines—Formyl as N-protective group s. 13, 56 Thiazoline ring opening... 

Ring opening and further ring closure of 2-imino-oxythiolan-l,3 derivatives (32) by water and/or methanol lead to the corresponding A-4-thiazoline-2-one (26) (Scheme 14) (30-32). 

Recently, Hoff and Blok report the reductive ring opening of 4-methyl-A-4-thiazoline-2-thione anion (80) (Scheme 39) (204) when treated with two equivalents of sodium in liquid amonia. Treatment of the prop-enethiolate (83) by 4N aqueous HCl affords 4-methylthiazole. The... 

Methylthio- and 2-ethylthio-4-methylthiazoles undergo reductive ring opening when treated by sodium in liquid ammonia (204). The first step of this reaction consists of the formation of the A-4-thiazoline anion (80). The next steps are analogous to those given for 80a to 83. 

Certain bifunctional nucleophiles allow cyclization after ring opening. The formation of 2-thiazolium salts (71JHC40S) and the analogous production of 2-amino-2-thiazolines (191) from aziridines and thiocyanic acid fall into this category (72JOC4401). 

Oxazolines and thiazolines are lithiated at the 2-position to give species that, like oxazole (Section III,B,1), are in equilibrium with ring-opened forms [70JA6676 90H(31) 1213]. Subsequent reaction with electrophiles can occur via either form (Scheme 139), with soft electrophiles (e.g.,... 

With thiazolines it is still possible to obtain silylated heterocycles, despite the initial reaction giving the ring-opened product, since like the situation with oxazole (Section II1,B, 1) the desired isomerization can be induced thermally (Scheme 140) [90H(31)1213]. However, the analogous isomerization cannot be induced in the oxazoline case (87S693). 

The synthesis of substituted cysteines can be accomplished via Michael addition reactions,]67124-126] by nucleophilic displacement,]127] from racemic thiazolines,]128] via aziridine ring opening,]129 and by asymmetric synthesis using a chiral auxiliary.]130] The details for some of these methods are described. 

The electrophilic properties of substituted 6//-l,3-thiazine-6-ones (208) in solution also shows reactivity at C-2 in acidic conditions and at C-6 in basic conditions. The regioselective reaction of 4-ethoxycarbonyl-2-phenyl-6//-l,3-thiazine-6-one with dimethylamine leads, after ring opening and reclosure, to two diasteriomeric 5-dimethylcarboxamido-4-ethoxy-carbonyl-2-phenyl-A2-thiazolines 209 and 210, whose structures were confirmed by X-ray diffraction studies on 210 (Scheme 84) (88BSF897). Com-... 

Thiazoline carboxamide 260 was transformed into thiazepine 261 by simple thermal treatment under the influence of ammonium chloride. This expansive rearrangement involved ring opening of the thioaminal function of 206 (Equation 21) <2005SL239>. 

The formation of l,2,5-trithiepan-4,6-dicarboxylates was explained by the mechanism depicted in Scheme 85 <20040BC2870>. This reaction presumably involves an initial reduction of 401 to A2-[l,2,3]thiazoline 405, which forms the S,C-biradical 406 by ring opening and release of nitrogen. Dimerization of 406 gives the S,C-biradical 407, which forms a C,C-biradical 409. A tandem intramolecular cyclization-expulsion of acrylic ester from 409 affords the trithiepine- dicarboxylates 402 and 403. An alternative pathway for the reaction would involve the formation of 408 from 406, which would be converted to 409 and then to the products. 

This metal-directed ring-opening of thiazolines, oxazolines and related compounds is a widespread reaction. In many cases, equilibria are set up between the heterocyclic compound and the imine. The position of these equilibria are metal-ion dependent. A typical example is seen in Fig. 5-81. The reaction of 2-(2-pyridyl)benzothiazoline (5.36) with copper(n) salts leads to the formation of complexes of the ring-opened tridentate form. 

More extensive rearrangements may also occur, and in Fig. 5-82 the ring opening of the bis(thiazoline) 5.37 by a methylthallium(in) complex is demonstrated. 

Figure 5-82. The ring opening of both thiazoline rings in 5.37 leads to the formation of a penta-dentate N2S2 ligand.

Direct transformation of thiazoline-azetidinones 2 into 3 -thio-substituted cephalosporins 6 has been performed by ring opening of the thiazoline moiety with sulfenyl chloride followed by ring closure with ammonia in dimethylformamide and simultaneous displacement of the allylic chlorine atom with the leaving thiolates. 

The inefficiency of the process [the yield of their 3-exomethylene compound was generally <70% with a ring-opened thiazoline as the primary byproduct (up to 30%) and 3-methylcephalosporin (XVIII) (up to approximately 7%) as a minor, but difficult to remove, secondary byproduct. 

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