Aldehydes, with aminothiazoles

Aldehydes, with aminothiazoles, 98 with A-2-thiazohne-5-ones. 432 Algicide, 438... 

Antischistosomal activity, of 5-nitro-2-aminothiazoles, 72 Antispasmodic activity, 150, 439 Antitrichomonal activity, 138 of 5-nitro-2-aminothiazoles, 72 Antitubercular activity, 139, 140,441,442 Antitumor activity, 149, 152 Antitussive, 144, 148 Antiulcer properties, 148 Antiviral, 138, 139, 140, 144,438 Appetite depressant, 147 Aprotic solvent, see Solvent effect Aromatic aldehydes, with aminothiazoles, 40... 

Both carbonyl groups of terephthaldehyde are reported to react with the exocyclic nitrogen of 2-aminothiazole yielding 1.4-phenylene bis(2-methyleneamino)thiazole. The same report describes the reactions of 2-amino-4-phenylthiazole with terephth aldehyde and salicylaldehyde as yielding 64 and 65, respectively (Scheme 45) (215), whose structures are based on ultraviolet and infrared spectra. 

Amino-5-nitrothiazole, on treatment with arenesulfonyl halides and dimethylformamide at 140 C, gives (5-nitro-2-thiazolyl)amidme (274) (Scheme 168) (507, 508). The condensation products of the reaction of 2-aminothiazole derivatives with various aldehydes are grouped in Tables... 

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar parts of thiourea (103) and a-haloketones or aldehydes to yield the corresponding 2-aminothiazoles (104a) or their 2-imino-A-4-thiazoline tautomers (104b) with no by-products (Method A, Scheme 46). 

Another example of imidazo[2,l-b][l,3]thiazole formation was reported by Adib et al. in their publication concerning eco-friendly catalyst-free MCR in the water [133]. Reaction of cyclohexyl isocyanide with diverse aromatic aldehydes and 2-aminothiazoles in water at 70°C allowed the isolation of heterocycles 96 in good-to-excellent yields (Scheme 43). According to the spectral data, compotmds 96 were determined as single products of the MCR. 

The previously published results [142, 143] devoted to the synthesis of thiazolo [3,2-a]imidazol-2-ones attracted attention of Krasovskii et al. [144] to synthesize corresponding ylidene derivates and to investigate biological activities, promising to be interesting for the medicinal chemistry. By heating 2-aminothiazoles with ethyl bromacetate and a variety of aromatic aldehydes at the appropriate temperature (either 80°C or reflux) in the glacial acetic acid with anhydrous sodium acetate, ylidene derivates of structures 102-104 were isolated (Scheme 48). 

For instance, the treatment of 2-aminothiazole or 2-amino-1,3,4-thiadiazole with a equimolar amounts of appropriate (hetero)aromatic or aliphatic aldehydes in the presence of an excess of mercaptoacetic acid under refluxing in anhydrous benzene gave diverse 2-substituted 3-(2-thiazolyl)- and 3-[2-( 1,3,4-thiadiazolyl)]-4-thiazolidinones 115a or 115b, respectively (Scheme 54). 

Aminothiazole, with acetaldehyde, 42 to 2-mercaptothiazoie, 370 4-Aminothiazole-2,5-diphenyl, to 2,5 di-phenyl-A-2-thiazoline-4-one, 421 Ammothiazoie-A -oxide, 118 2-Aminothiazoles. 12 acidity of, 90 and acrylophenone, 42 acylations of, with acetic acid. 53 with acetic anhydride, 52 with acyl halides, 48 with chloracetyl chloride, 49 with-y-chlorobutyrylchloride, 50 with 0-chloropropionylchloride, 50 with esters, 53 with ethy acrylate, 54 with indoiyl derivatives, 48 with malonic esters, 55 with malonyl chloride, 49 with oxalyl chloride, 50 with sodium acetate, 52 with unsaturated acyl chloride, 49 additions to double bonds, 40 with aldehydes, 98 alkylations, with alcohols, 38 with benzyhydryl chloride, 34 with benzyl chloride, 80 with chloracetic acid, 33 with chloracetic esters, 33 with 2-chloropropionic acid, 32 with dialkylaminoalkyl halides, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38... 

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar quantities of thiourea and a-halo ketones or aldehydes to yield the corresponding 2-aminothiazoles (Scheme 167) (l888LA(249)3l). The reaction occurs more readily than that of thioamides and can be carried out in aqueous or alcoholic solution, even in a distinctly acid medium, an advantage not shared by thioamides which are often unstable in acids. The yields are usually excellent. A derived method condenses the thiourea (2 mol) with the non-halogenated methylene ketone (1 mol) in the presence of iodine (1 mol) or another oxidizing agent (chlorine, bromine, sulfuryl chloride, chlorosulfonic acid or sulfur monochloride) (Scheme 168) (45JA2242). 

As discussed in Section 3.06.5 aminothiazoles react with alkyl halides to give mainly the product of alkylation at the endocyclic nitrogen when the reaction is conducted in the absence of strong bases with acyl and sulfonyl halides, the exocyclic nitrogen becomes the main nucleophilic site. The reaction of 2-aminothiazoles with heterocyclic or aromatic aldehydes show ample differences depending on the various amine-aldehyde pairs <9lS62i>. In general the azomethine derivatives are obtained by a suitable procedure which has to be followed in each case. The increase of the amine/aldehyde ratio leads to bis-amines as the major products of the reaction. 

The reaction of 2-aminothiazole and 2-aminobenzothiazole with 2-benzoyl-2-bromoacetate has been employed in the preparation of several fused imidazole systems <89JHC1875>. a-Bromo ketones attack the ring nitrogen of 2-aminothiazoles to give the salts (160). The same type of reaction takes place with ethylbromoacetate (Scheme 39). Basihcation of (160) affords the imines (I6I) which are intermediates in the synthesis of imidazo[2,l-h]thiazoles <89JCS(P1)643>. On the other hand, when an a-bromo aldehyde is made to react with 2-aminothiazoles, the salt (162) is formed directly leading to (163) after basification. 

Supports 3e and 3f derived from a related linker with only one me-thoxy group ortho to the aldehyde have been reported [140] to have a more reactive aldehyde group than 3c or 3d due to lower steric hindrance. Resin 3e was used to synthesize aminothiazoles, which were cleaved under acidic conditions [141]. Thus, amines were anchored reductively to 3e and converted to resin-bound thioureas by reaction with Fmoc-isothiocyanate followed by deprotection. Cyclization by reaction with a-bromomketones gave the desired heterocycles, which were cleaved from the resin by treatment with TFA-H2O (19 1) (Scheme 4). 

In 2013, Adimurthy and co-workers reported a TM-free NaOH-catalyzed N-alkylation reaction of 2-aminothiazoles, 2-aminobenzothiazoles, aminopyrimidines, and aminopyridines with benzyhc and heterobenzyhc alcohols under air (Scheme 43) [203]. In condition optimization, the authors found the model reaction of 2-aminobenzothiazole and 4-chlorobenzylalcohol under air afforded a higher yield of the product (93 %) than the one under nitrogen (90 %). Therefore, along with other results of mechanistic studies and the authors own previous work on based-catalyzed imine synthesis from alcohols and amines [204], they proposed that alcohol oxidation to aldehyde by air in the presence of bases is the initiation step of... 

Bridgedhead thiazolo[3,2-a]pyrimidines, and their isosteres occupy a unique place in medicinal chemistry due to their wide application as drug and drug-intermediates [7-11]. Several methods are known for synthesis of thiazolo[3,2-a]pyrimidine derivatives, from 2-mercaptopyrimidines and a-halo ketones, and by cyclocondensation of a-aminothiazoles with P-diketones, P-keto aldehydes, and their acetals, P-chlorovinyl ketones and aldehydes. 

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