5- Aminothiazoles rearrangement

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

The Curtms rearrangement has been used to prepare 5-aminothiazole (11) (60.61), 4-methyl-5-aminothiazole. 2-chloro-5-aminothiazole (58), and 2.4-dimethyl-5-aminothiazole (62) (Scheme 11). Heating the corresponding azides yield carbamates that resist hydrolysis but react with acetic anhydride to give the 5-acetylaminothiazoles. 

The main features are the molecular ions as the base peak and the M-t-1 ions arising from another species. For 2-aminothiazole the m/e 73 ion (M-HCN) is shifted to m/e 75 in the spectrum of the dideuteroamino derivative and, therefore, largely arises via rupture of 2-3 and 4-5 bonds (Scheme 18). This fragmentation process could involve the kind of intermediates postulated in photochemical rearrangements (see Chapter III, Section IX.3.B). The other fragments fit well the general pattern of fragmentation proposed by Clarke (136). 

Experimental requirements for the isolation of these nitramino derivatives are developed in Ref. 87. They rearrange easily to ring nitro-substituted isomers (see Section V.6). In the 2-aminothiazole series, nitration may proceed through direct electrophilic substitution competing with rearrangement of nitramino derivatives. Dickey et al. have shown that the rearrangement proceeds rapidly in 96% sulfuric acid at 2(fC, but in 85% sulfuric add it is very slow so. according the concentration of add various mechanisms can participate in the formation of the 5-nitro derivative. 

Sulfonation under mild conditions is reported to yield thiazolyl-2-sulfamic acid, which, when heated in H2SO4. rearranges to 2-aminothiazole-5-sulfonic acid (16. 374. 390. 391). Postovskfi. however, reports exactly the opposite rearrangement (367). and spectroscopic evidence supports his conclusion (368) (see Section III.5). 

Carbocations derived from the alcohol are probably the reactive species, but data concerning by-products expected with carbocationic intermediates are lacking. Rearrangement of 2-alkylaminothiazoles to 2-amino-5-alkylthiazoles may also explain the observed products 2-aminothiazole with benzyl chloride yields first 2-benz Iaminothiazole (206). which then rearranges to 2-amino-5-benzvlthiazole (207) (Scheme 130) (163. 165. 198). 

Attack on the electrophilic C-2 may occur as in the 2-aminothiazoles series, which probably explains the rearrangements observed in acidic medium (121, 711, 712, 723, 724), in aqueous medium with NaOAc (725), or with aqueous NaHCOj (725) (Scheme 232). That the initial attack probably involves the C-2 atom is substantiated by the fact that this rearrangement occurs under extremely mild conditions for 2-iinino-3-substituted-5-nitro-4-thiazolines (725). As the whole mechanism proposed (see p. 92) is reversible, when imino derivatives are submitted to such rearrangement conditions the rearrangement is expected to occur faster if steric interaction between 3- and 4-substituents exists in the 2-imino isomer. Another reaction may occur in acidic medium phenylimino-2-bipheny]-3,4-4-thiazoline hydrolyzed with hydrochloric acid gives the corresponding 4-thiazoline-2-one and aniline (717). 

Cyclic amidines (213) react with chlorocarbonylsulfenyl chloride to give bicyclic 1,2,4-thia-diazoles. The product isolated from this reaction depends on the mode of addition. When (213) is added to chlorocarbonylsulfenyl chloride, 3-oxo derivatives (214) are isolated via the postulated intermediate (215). Addition of chlorocarbonylsulfenyl chloride to (213) leads to 5-oxo derivatives (216), via the proposed bis(intermediate) (217) (Scheme 47) <84CHEC-I(6)463). Cyclic amidines (213) have also been treated with 1-chloro-l-phenyliminomethanesulfenyl chloride (210) to afford 2>H-1,2,4-thiadiazoles (218). The other possible product from this reaction, the 2/7-isomer (219) has been shown to be unstable, rearranging to a benzothiazole. Heterocycles (213) which have been used in this transformation include 2-aminopyridine, 3-aminopyridazine, 2-aminobenzothiazole, 2-aminopyrimidine and 2-aminothiazole (Equation (33)) <86S1027>. 

Amino-5-nitrothiazole is prepared (59JOC187, 55JOC499) by the reaction between 2-chloroacetaldehyde and thiourea followed by nitration of the free amine. It has been shown that the nitration proceeds by the N-nitration of the 2-amino group followed by rearrangement. Several other derivatives of 2-aminothiazole have been described in patents but none have reached any commercial significance. 

The recently reported rearrangement (1581) of 2-allylamino-4-carboxamido-5-aminothiazoles to 4-aminoiinidazole-5-carboxamide in presence of sodium bicarbonate probably involves the electrophilic reactivity of C-2, which allows the ring opening. 

Arylsulfonylbenzimidoyl chlorides, with aminothiazoles, 50 Arylsulfonyl halides, 98, 115 Azide, with azothiazoles, 111 to carbamate, 16 Curtius rearrangement of, 15, 16 See also Sodium azide Azido thiazoles, 113 azidothiazole-thiazolotetrazole, 113 reactions of, 113... 

Barium thiocyanate, 118 Base catalysis, 34 in acylations, 47, 48 of chelate formation, 95 of clevage, 128 of cydization, 127 in hydrolysis, 115 Basicity, of 2-aminothiazole, 90 of 2-imino-4-thiazolines, 124 Beckmann rearrangement, of oxime, 16 Benzaldehyde, with alkyl-acetamidothi-azole, 46... 

Sulfonimidothiazolines, 317, 318 Sulfonyl halides, with 2-aminothiazoles, 69 Sulfur (Sg), in synthesis of, A-4-thiazoline-2-thione, 373 Sulfur compounds, 69 Sulfuric acid, with alcohols, 38, 47, 80, 90 in bromination, 77 dealkylation by, 39 deuterated, 92 diazotization with, 66 in nitrations, 72 rearrangements in, 73, 113 Sulfuryl chloride, 432 Symbiotic behavior, see HSAB theory Symmetry. C2v and C2p, 120 Synthetic fibers, 154... 

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