Quinazolines are unique class of compounds possessing exceptional antibacterial activity. Quinazolines class obtains its typical antibacterial activity due to its toxicity from‘hetero’ ring. Known to be the last line of protection against deadly TB bacteria, there are about
twenty different quinazoline compounds used in pharma industry. One of the widely used precursors for synthesis of these drugs is 4-chloro-2-phenylquinazoline. In the present research, aminobenzamide and benzoyl chloride are reacted to obtain the cyclized intermediate, 2-phenylquinazoline,
which on subsequent treatment with POCl3 forms in 4-cholro-2-phenyl quinazoline. This reaction takes about four days to finish with maximum yield of around 60%. A modification was done using silica coated magnetic nanoparticles (Fe3O4@SiO2) as solid
support to further improve the yields attaining about 80% and reduction of reaction time to half. Based on the results obtained, it was concluded that the solid support facilitates the adsorption of acid chloride and also provides the catalytic surface for condensation reaction, due to the
acidic nature of the silica gel. The POCl3 reaction uses the nanosilica surface to produce 4-chloro phenyl-2-qinazoline in 80% overall yield. The reason for improved yield could be increase in acidic surface area which could speed up the quinazoline cyclization. Though material
chemistry supports are known to improve reaction yields, use of silica coated magnetic nanomaterials towards the quinazoline synthesis is reported for the first time. The characterization data of Fe3O4@SiO2 particles has shown that batch to batch consistency
exists in synthesis and it can be used in the pharma industry.
Our group reported pyrimidine derivatives as one of the first T-type calcium channel blockers [1,2]. The pyrimidine ring is pharmacologically important functional group especially in the broad fields of cardiovascular and psychotic drugs [3-5]. The pyrimidine group is recently been reported with numerous pharmacological applications emphasizing the direction of medicinal chemistry field and significance of heterocyclics [6-10]. Though it is believed that pyrimidines are less utilized as pharmacological synthons compared to other rings like dihydropyrimidine [11,12], pyridines [13,14], furons [15,16], thiophenes [17], thiazides [18], etc., the evolution of newer medicinal chemistry leads are limited [19]. This is because the pyrimidine synthesis reactions usually result in lower reactions yields compared to other heterocyclics [20,21]. The recent spurt in interest of pyrimidine compounds necessitates development of viable synthetic methods. A simple condensation reaction of acetoacetate or malonate with guanidine compound
Broad spectrum pesticides are molecules which act across a range of pests. The popular class of compounds with this property are thiacloprid, nitenpyram, ethaboxam, silthiofam, 3,3,4,4-tetrachloro tetrahydro thiophene etc. Interestingly, all these compounds possess at least one heterocyclic ring like thiophene, furan, and imidazole etc. in their structure. Among the synthons available for synthesis of neonicotinoids, tetrachlorothiophene is unique. The bulk scale synthesis of tetrachlorothiophene is reported only by cyclization of hexachloro-1,3-butadiene. The reaction yields of synthesis of this synthon are around 45%. We report silica-coated magnetic nanoparticles as a generic catalyst for this cyclization reaction yielding tetrachlorothiophene. The yield improvement is 50-60% more compared to original yield. The distillate crystallization in methanol yielded >98% pure compound compared to typical 90-92% in conventional process. The proposed reaction uses reusable silica-coated 40 nm size magnetic nanoparticles and the catalyst itself is of low cost and reaction conditions are mild.
Quinolines are an interesting class of moieties with various medicinal chemistry uses. The most prominent is their ability to be used as the last line of therapy for bacterial and viral infections including recent COVID-19. The synthesis of quinoline is through a cyclization reaction and overall reaction yields are about 20%. The bulky ring and the associated crowding of functional groups limit the catalyst options. In this publication, the use of Fe
3
O
4
@SiO
2
for enhancing yield improvements, especially for heterocyclics is reported. The use of the 40 nm sized silica functionalized magnetite nanoparticles seems to help in both condensation and cyclization steps of representative 2-methyl-6-nitroquinoline. Reaction time reduction due to surface enabled catalysis of nanoparticles is 110 min to 80 min. The reaction yield has doubled due to the presence of catalyst and the mechanism suggests this drastic result is due to stabilization of unstable intermediate on the acidic surface of the silica coating. This near homogeneous catalysis of 40 nm sized, silica functionalized, magnetite nanoparticles have far reaching applications in bulk drug industry for drugs like chloroquine & hydroxychloroquine, the two essential drugs for prophylactic use for COVID-1.
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