Synthesis of 2,2-Disubstituted-5-Cyanocyclopentanones

Abstract

The synthesis of a series of 2,2-disubstituted-5-cyanocyclopentanones by hydrolysis of the precursor 3,3-disubstituted-2-amino-1-cyanocyclopente~es (2,2-disubstituted-5-cyanocyclopentanoneirnines) is described. The new compounds possess the following substituents: dimethyl, diethyl, phenyl hydrogen, and ethyl phenyl.

Multiple pathways in the synthesis of new annelated analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (emivirine)

“…First 7 was α-alkylated using a modified procedure of Wallingford et al 11 to give 2-(3,5-dimethylphenyl)hexanedinitrile (8) in 61% yield. A subsequent ring-closure reaction with sodium hydride in a Thorpe-Ziegler reaction using the method of Kulp et al 12 afforded 9 in 93% yield.…”

“…7-(3,5-Dimethylphenyl)-6,7-dihydro-5H-cyclopenta[e][1,3]oxazine-2,4-dione (12) was synthesized from 10 by treatment with N-(chlorocarbonyl)isocyanate 15 in 35% yield (Scheme 3). The isomeric oxazine 12a was isolated in 11% yield as a byproduct because the aromatic conjugated enol tautomer is most likely the preferred enol tautomer of 10, which undergoes a reaction with N-(chlorocarbonyl)isocyanate.…”

“…]oxazine-2,4-dione(12) (0.40 g, 1.6 mmol) was refluxed with aqueous ammonia (11 ml, 25%) for 24 h. Cooling to rt gave a light brown precipitate which was filtered off and purified by recrystallisation in EtOH which gave 13 (0.37 g, 90%) as light brown crystals; mp 299-300 ЊC (EtOH); (Found: C, 69.8; H, 6.3; N, 10.8. C 15 H 16 N 2 O 2 , 0.1 H 2 O requires C, 69.8; H, 6.3; N, 10.9%); R f 0.25 (10% MeOH-CH 2 Cl 2 ); δ H (DMSO-d…”

Alternative Route to the Diisocyanate Building Block 1,4-Diisocyanato-4-methylpentane (DIMP)

“…All NMR data were collected on a Bruker Avance II 300-MHz spectrometer ( 1 H at 300 MHz, 13 C at 75 MHz) using deuterochloroform (CDCl 3 ) as a solvent. NMR data (free induction decays) were processed using NUTS software from Acorn NMR (Livermore, CA).…”

Synthesis and hydrolysis of hindered 2,2-disubstituted 5-cyanocyclopentanonimines

“…Compounds la, Ha, Ilia, and IVa were synthesized by our previously developed route. 3 Acid hydrolysis of these iminonitriles (existing mainly as l-amino-2cyanocyclopentene tautomers8,6,9) proceeded in the order of difficulty predicted. Whereas type a compounds with R and R' = hydrogens, dimethyls, diethyls, and ethylphenyl were hydrolyzed readily to their keto nitriles,3 similar conditions were ineffective with the compounds reported here.…”