264606-50-0

Upstream product

• 88000-53-7 α-hydroxy-4-nitro-α-phenylbenzeneacetonitrile 
• 1144-74-7 4-nitrobenzophenone 
• 935761-26-5 2-(4-Nitrophenyl)-2-phenyl-2-((trimethylsilyl)oxy)acetonitrile 

Downstream Products

• 264606-51-1 (+/-)-4-amino-α-hydroxy-α-phenylbenzeneacetamide 

Relevant academic research and scientific papers

Hydration of Cyanohydrins by Highly Active Cationic Pt Catalysts: Mechanism and Scope

Cyanohydrins (α-hydroxy nitriles) are a special type of nitriles that readily decompose into hydrogen cyanide (HCN) and the corresponding carbonyl compounds. Hydration of cyanohydrins that are readily available through cyanation of aldehydes and ketones provides the most straightforward route to valuable α-hydroxyamides. However, due to low stability of cyanohydrins and deactivation of the catalysts by the released HCN, catalytic direct hydration of cyanohydrins still remains largely unsolved. As a general trend, cyanohydrins containing bulkier substituents, such as α,α-diaryl cyanohydrins, degrade more quickly and thus are more difficult to be hydrated. Here, we report development of cationic platinum catalysts that exhibit high reactivity for hydration of various cyanohydrins. Detailed mechanistic investigations for hydration of nitriles by (PμP)Pt(PR2OH)X(OTf) reveal a catalytic cycle involving the formation of a five-membered metallacyclic intermediate and subsequent hydrolysis via attacking on the phosphorus of the secondary phosphine oxide (PR2OH) ligand by H2O. We discovered that Pt catalyst A bearing the electron-rich, appropriately small-bite-angle bisphosphine ligand provides super reactivity for hydration of cyanohydrins. The hydration reactions catalyzed by A proceed at ambient temperatures and occur with a wide variety of cyanohydrins, including the most difficult α,α-diaryl cyanohydrins, with good turnover numbers.

Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides

We report the palladium(II)-catalyzed transfer hydration of cyanohydrins to α-hydroxyamides by using carboxamides as water donors. This method enables selective hydration of various aldehyde- and ketone-derived cyanohydrins to afford α-mono- and α,α-disubstituted-α-hydroxyamides, respectively, under mild conditions (50 °C, 10 min). The direct conversion of fenofibrate, a drug bearing a benzophenone moiety, into a functionalized α,α-diaryl-α-hydroxyamide was achieved by means of a hydrocyanation-transfer hydration sequence. Preliminary kinetic studies and the synthesis of a site-specifically 18O-labeled α-hydroxyamide demonstrated the carbonyl oxygen transfer from the carboxamide reagent into the α-hydroxyamide product.

4,5-dihydro-isoxazole derivatives and their pharmaceutical use

The present invention is concerned with the compounds of formula wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; —A1═A2—A3═A4— is a pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, —N—, —O—, —CR5R6—, amide ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole, isoxazole or thiazole; L represents Ar or Het; R1represents hydrogen, halo, hydroxy, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, cyano, guanidine, nitro, NR17R18, an optionally substituted C(1-6)alkyl or C(1-6)alkyloxy; R2and R3each independently represent hydrogen, halo, C(1-6)alkyloxy or an optionally substituted C(1-6)alkyl; R5and R6each independently represent hydrogen, hydroxy, halo, an optionally substituted C(1-6)alkyl, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, C(1-6)alkyloxy, cyano, (C═O)R25, (C═O)OR16, (SO2)R16, aminocarbonyloxy, aminoC(1-6)alkyl, NR17R18, N3, Ar or Het; or R5and R6together with the carbon atom to which they are attached, form an Ar or Het; Ar represents an optionally substituted C(6-14)aryl; Het represents an optionally substituted C(1-14)heterocycle; or a N-oxide, pharmaceutically acceptable addition salt, quaternary amine or stereochemically isomeric form thereof; the processes for their preparation and compositions comprising them. It further relates to their use as a medicine.