Thiazole benzothiazole synthesis

The term C-nucleoside was only coined after isolation and characterization of the first member of this class pseudouridine, in 1975 [97ACH(ip)]. Before that, alditolyl derivatives of some heterocycles (acyclo C-nucleo-sides) were known both as natural products (alditolyl pteridines or biopterins) as well as products of syntheses (e.g., alditolyl derivatives of imidazoles, benzimidazoles, thiazoles, benzothiazoles, 1,2,3-triazoles, quinoxalines, and flavazoles) and were classified as carbohydrate derivatives of heterocyclic compounds. After isolation of pseudouridine, other naturally occurring members were successively isolated, characterized, and synthesized. It is worth mentioning that synthesis preceded isolation in two cases 9-dea-zaadenosine and pyrrolosine. Comparison with the synthetic compounds facilitated structure elucidation in one case (9-deazaadenosine) and structure reassignment in the other (pyrrolosine). 

The most important principle of synthesis is cyclocondensation. Oxazoles, benzoxazoles, isoxazoles, 4,5-dihydroisoxazoles, thiazoles, benzothiazoles, isothiazoles, imidazoles, pyrazoles and 4,5-dihydropyrazoles are synthesized by this method. 

Diazadienes have been used in organic synthesis for the preparation of various heterocyclic compounds. Alkylation of 1,3-diazadienes 207 and the benz-fused analog 210 at the nitrogen atom by aryl acyl bromides provided the iV-alkyl amidinium bromides 208 and 211, which underwent annulation to the 2,3-dihydro-imidazo[2,l-A]thiazole 209 and imidazo[2,l- ]benzothiazoles 212, respectively (Equations 92 and 93) <2001S741, 2002J(P1)741>. 

In the middle of the 1950s, Knott reported the synthesis of dyesmffs based on benzothiazole derivatives. Alkylation of Al-methylbenzo-l,3-thiazole-2-thione with a-bromoacetophenone and deprotonation of the resulting thiocarbonylium salt 5 yielded, after spontaneous desulfurization of the intermediate thiirane (7), the alkylidene derivative 8 (18) (Scheme 5.1). In order to rationalize the reaction, thiocarbonyl ylide 6 was proposed as the precursor of thiirane 7. To the best of our... 

The Balz-Schiemann synthesis can be applied not only to substituted anilines but also to aminobiphcnyls1,131 or amino-substituted fused polyaromatic compounds, such as naphthalene,1114,119,129 anthracene,136 phenanthrene,1135 acenaphthene,133 fluorene,1,131,134 benzanthracene,130 136 pyrene,136 chrysene,136 fluoranthene,131 fluorenone,1,131 anthra-quinone,1,137,139,140 benzanthrone,1,117,118 phenanthraquinone,138 or xanthone.132 Fluorinated pyridines,1,141"146 methylpyridincs,126,147 149 pyridinecarboxylic acids,150 quinolines,1,151 isoquinolines,152 quinazolone,1 thiazoles,153,154 isothiazoles,156 benzothiazoles,157 thiadiazoles,155 and thiophenes154 can also be obtained from the corresponding aminated heterocycles. Modified Balz-Schiemann methods are recommended for amino nitrogen-containing heterocycles, the diazonium salts of which are rather water-soluble and unstable (a violent explosion was reported for pyridine-3-diazonium tetrafluoroborate).159 These new techniques have also been specially adapted for pyrazol-, imidazol-, or triazolamines which fail to react under classical conditions.158... 

Several derivatives of thiazole have commercial uses. One of these is 2-aminothiazole, which has shown a high toxicity to experimental animals. Benzothiazole is another related compound used in organic synthesis. Thiazoles are used as rubber vulcanization accelerators. Benzothiazole,... 

A large body of information on the methods of synthesis, application, structure, and properties of all known five-membered nitroazoles - pyrazoles, imidazoles, triazoles, tetrazoles, oxazoles, isoxazoles, oxadiazoles, thiazoles, isothiazoles, thiadiazoles, selenazoles, selenadiazoles, and their benzo analogs - indazoles, benzimidazoles, benzoxazoles, benzisoxazoles, benzoxadiazoles, benzothiazoles, benzoisothiazoles, benzothiadiazoles, benzotriazoles, benzoselenazoles, and ben-zoselenadiazoles has been systematized, summarized, and critically discussed in this monograph. 

The intensity of activity in the field of thiazole and benzothiazole research reflects the importance of these heterocycles in organic and biological chemistry. There has therefore been a large volume of synthesis literature produced since 1995. The following section has been ordered according to the fragments generated by retrosynthetic analysis, which are shown in Scheme 53. 

Benzothiazole derivatives as vulcanization accelerators 78YGK395. Chlorinated thiazoles, synthesis of 85S586. 

Acetic formic anhydride is a versatile reagent in organic synthesis (review [3823]), for example, when it is stirred with an o-aminothiophenol. a 2-unsub-stituted benzothiazole is formed. Aminothiophenols, like their oxygen counterparts [2111], are cyclized by carboxylic acids or their esters, and also by dichloromethyleneammonium salts (review [2549]) to give good yields of benzo-thiazoles [2548]. The use of a dithioic ester is shown in Section 1.2 [2860]. 

The synthetic applications of benzothiazoles appeared to be limited by the fact that the thiazole ring cannot be hydrolytically cleaved. However, this problem was solved by quatemization followed by reduction with NaBH4 to produce 3-methyl-2,3-dihydrobenzothiazole, as shown in the synthesis of cyclohexene-1-carbaldehyde [104] ... 

Despite the use of well-established methods to construct thiazoles and benzothiazoles, several interesting methods employing varied strategies continue to emerge. For example, Zhan and co-workers at Xiamen University have reported a facile one-pot synthesis of three differently substituted... 

---