Hantzsch-type condensation

Substituted 5// -thiazolo[3,2-a]pyrimidine derivatives 54 (R = n-propyl, 4-hydroxypheyl, 4-methoxypheyl Ri = ethoxy, methyl Ar = subs, phenyl), are useful as acetylcholinesterase(AChE) inhibitors (Scheme 24), were S3Tithesized by the Hantzsch-type condensation of dihydropyrimidines 53 with substituted phenacyl chlorides [47, 48],... 

Although the exact reaction mechanism for this three-component condensation reaction was not confirmed in [193, 194], the hypothesized mechanism is likely to involve the initial base-catalyzed formation of the Michael adduct, and its subsequent reaction with the aminopyrazole component to furnish the tricyclic intermediate (Scheme 3.63). Elimination of water from this intermediate leads to the formation of the classic Hantzsch-type dihydropyridine... 

Carbon-11 labelled calcium channel antagonists C-nifedipine, C-nisoldipine, C-nitrendipine and C-CFj-nifedipine possessing vasodilating and hypotensive properties have been synthesized using a modified Hantzsch-type cyclocondensation proce-dure . Condensation of aldehydes 242, 243 and 244 with 3-aminocrotonic acid esters 245, 246, 247 and with acetoacetic ester 248 produced in one pot after 12 hours reflux in dry ethanol the methyl sulphonylethyl protected dihydropyridines 249-252. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the dihydropyridine monocarboxylic acids 253-256 gave potassium salts in situ, and subsequent methylation with CH3I produced the corresponding labelled title compounds 257-260 (equation 102),... 

The reactivity of pyridazine-3- and 4-carbaldehydes towards active methylene reagents under the conditions of Knoevenagel, Wittig, and Hantzsch-type reactions has been examined. The 4-aldehyde reacts readily with malononitrile and methyl cyanoacetate, and less readily with triethyl phos-phonoacetate, indane-l,3-dione and alkyl acetoacetates/ammonia (e.g.. Scheme 52). Condensation with nitroethane is successful, but nitromethane gives an unstable intermediate which decomposes. The 3-aldehyde has similar reactivity to the 4-aldehyde, but some reactions are unsuccessful due to reduced reactivity, or instability of the products <90JHC1313>. 

Mixing 1 first with 5 (entry b) yields the isothiouronium salts of type 8 which react with 4 in a Hantzsch-ty condensation to yield imidazoles of type 9 (again 27 compounds). In a similar way, isothiourea 8 (R =H) reacts with two equivalents of 4 to give imidazoles 10 (9 compounds). For the case where the reaction described in entry c is performed as a combinatorial one-pot synthesis in one reaction vessel, all possible 27 permutations of 10 can be obtained. 

II. Thiazoles from a-Halocarbonyl Compounds and Derivatives. Hantzsch s Synthesis. and Related Condensation (Type I).169... 

Hantzsch s Synthesis (Type A, S—C—N + C—Q.— Various forms of Hantzsch s synthesis continue to be widely employed for producing both old and new types of thiazole derivatives (see Table 1). In a useful procedural variation, a thioamide is generated from the corresponding amide by the action of phosphorus pentasulphide in dioxan, and condensed in situ with the a-halogenocarbonyl compound. The effectiveness of the... 

In recent years, synthesis of pyrroles has drawn the attention of chemists. Traditional methods used for pyrrole synthesis include the Hantzsch reaction [45] and the Paal-Knorr condensation reaction [46,47], The latter is the most widely used method, which involves the cyclocondensation reaction of 1,4-dicarbonyl compounds with primary amines to produce substituted pyrroles. In addition, there are several methods such as 1,3-dipolar cydoaddition reaction, aza-Wittig reaction, reductive coupling, and titanium-catalyzed hydroamination of diynes. Scheme 1 shows several catalysts used in this type of reaction [44]. 

Hantzsch Heterocyclization Henry Reaction Hofmann Rearrangement Knoevenagel Condensation Mannich Type Reaction Michael Addition enolate... 

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