Solvent parallel synthesis

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

Microwave-assisted reactions allow rapid product generation in high yield under uniform conditions. Therefore, they should be ideally suited for parallel synthesis applications. The first example of parallel reactions carried out under microwave irradiation conditions involved the nucleophilic substitution of an alkyl iodide with 60 diverse piperidine or piperazine derivatives (Scheme 4.22) [76]. Reactions were carried out in a multimode microwave reactor in individual sealed polypropylene vials using acetonitrile as solvent. Screening of the resulting 2-aminothiazole library in a herpes simplex virus-1 (HSV-1) assay led to three confirmed hits, demonstrating the potential of this method for rapid lead optimization. 

Scheme 4.24 Solvent-free parallel synthesis under microwave conditions (domestic oven).

Sauvagnat, B., Lamaty, F., Lazaro, R. and Martinez, J., Poly(ethylene glycol) as solvent and polymer support in the microwave assisted parallel synthesis of aminoacid derivatives, Tetrahedron Lett., 2000, 41, 6371. 

A rapid parallel solvent-free synthesis of a representative 28-membered library of phthalimides was achieved utilizing a household microwave oven under highly optimized conditions [35]. Thus, the highest irradiation area inside the household microwave oven was determined to ensure better reproducibility of results (Scheme 12). 

Scheme 12 A rapid parallel solvent-free synthesis of a library of phthalimides...

Heterocyclic chemistry was facilitated by microwave-expedited solvent-free chemistry utilizing mineral supported reagents [65]. The scope now includes parallel synthesis [66]. A representative multi-component condensation to create a library of imidazo[l,2-a]pyridines, imidazo[l,2-a]pyrazines and imidazo[ 1,2-a]pyrimidines is depicted in Scheme 12 [67]. 

---