Hydrolysis, acetal enamine

When 14 was heated in ethanol under reflux with hydrochloric acid, (Z)-[4-(5-hydroxy-3-methyl-l-phenyl-lH-pyrazol-4-ylmethyhdene)-5-oxo-l-phenyl-4,5-dihydro-lH-pyrazol-3-yl] acetate (17) was obtained in 75% yield, identical with the compound prepared from 14 and 12 in 90% yield. Apparently, partial hydrolysis of enamine 14 took place to furnish in situ pyrazole 12, which reacted as the C-nucleophile with the non-hydrolysed enaminone 14 to afford 17. Compounds 15 were heated with 2 equivalents of DMFDMA in DMF under reflux to give pyrazolo[4,3-c] pyridines 18 in moderate yields. Cyclization proceeds by incorporation of DMFDMA as a Ci synthon between the nucleophilic NH and CH2 groups. In the reaction of 15 (R =4-hydroxyphenyl) with DMFDMA, methylation of the phenolic hydroxy group also took place to give the 5-(4-methoxyphenyl)pyrazolo[4,3-c]pyridine (18 R=4-methoxyphenyl) (Scheme 7). 

Acetal formation Glycoside synthesis, from carbohydrates and alcohol Hydrolysis of enamines Epoxidation of fats by H2O2, followed by hydrolysis to transglycol... 

The tetrasubstituted isomer of the morpholine enamine of 2-methyl-cyclohexanone (20) because cf the diminished electronic overlap should be expected to exhibit lower degree of enamine-type reactivity toward electrophilic agents than the trisubstituted isomer. This was demonstrated to be the case when the treatment of the enamine with dilute acetic acid at room temperature resulted in the completely selective hydrolysis of the trisubstituted isomer within 5 min. The tetrasubstituted isomer was rather slow to react and was 96% hydrolyzed after 22 hr (77). The slowness might also be due to the intermediacy of quaternary iminium ion 23, which suffers from a severe. 4< strain 7,7a) between the equatorial C-2 methyl group and the methylene group adjacent to the nitrogen atom, 23 being formed by the stereoelectronically controlled axial protonation of 20. 

This value is in excellent agreement with the calculated free energy value by the consideration of various nonbonded interactions in the epimers (69 and 70) [(2 X 1,3-diaxial Me—H interaction) — (1 x 1,3-diaxial Me—H interaction + 1 X l,2- < Me—H interaction) = (0.9 x 2) — (0.9 + 0.6) = 0.3 kcal/mole]. Hydrolysis of the enamine with dilute acetic acid gave a 3 2 mixture of cis and trans isomers of the ketone, thus confirming the assignments made to the enamine components. 

The rearrangement of the 5-cyano-4,5-dihydro-l//-azepine (93) to furo[2,3-6]pyridine (95 Scheme 9) with sodium nitrate in glacial acetic acid or with silver nitrate in aqueous ethanol proceeds by initial protonation at either C-3 or C-6 followed by hydrolysis to the cyanooctanedione ester (94). By carrying out the rearrangement with an acid ion exchange resin it is now possible to isolate the dione ester (77CJC4061). Likewise, the hydrolysis of the tetrahydro-2-benzazepine (96) to an 0 -(anilinoalkyl)benzophenone is an example of proton attack at the /3 -carbon of the enamine system (77JA5045). 

Condensation of the pyrrolidine enamine of cyclohexanone with l,l-dicyano-2,2-dimethylcyclopropane proceeds smoothly in refluxing dry xylene and gives the expected adduct in 76% yield. Recrystallisation of the adduct from 95% ethanol, however, gave a 91% yield of a product which no longer contained the pyrrolidine group but whose spectral data clearly showed the presence of a ketone group and an enaminonitrile function. Hydrolysis of this latter product with phosphoric acid/acetic acid gave 5-(2-oxo-4,4-dimethylcyclopentyl)pentanoic acid in 83% yield. 

Scheme 32 illustrates an application of a 6-exo-trig radical cyclization in the total synthesis of ( )-mossambine (166) [68-69]. Indoloazepine 160 was obtained from tiyptamine in four steps (30% overall yield). Pyrolysis of 160 in refluxing toluene in the presence of 2-acetoxyacetaldehyde led to transient generation of an enamine acrylate 161, which stereoselectively formed the tetracyclic vinylogous urethane 162. Hydrolysis of the acetate... 

The intermediate alkylation products from enamines are hydrolyzed, even by water.266 The adducts with a,/3-unsaturated ketones are more stable, and in this case hydrolysis by aqueous acetic acid— sodium acetate is required.32 Further condensation to give bicyclic unsaturated ketones frequently occurs.267, 268... 

Ozonolysis of vinylpyrazine in methanol at — 30° furnishes pyrazine aldehyde in 73% yield.196 Vinylpyrazine undergoes a variety of addition reactions and pyrazylethyl derivatives of amines, ketones, ethyl phenyl acetate, phenylacetonitrile, and acetamide have been obtained.197-199 2-(2-Pyrazylethyl)cyclohexanone (42) has been prepared both by the condensation of vinylpyrazine with cyclohexanone in the presence of sodium metal and by interaction of vinylpyrazine with the pyrrolidine enamine of cyclohexanone followed by hydrolysis.200... 

Methoxy-a-tetralone (137), which on formylation at room temperature followed by treatment with n-butanethiol in presence of p-toluenesulfonic acid gave the compound (138), which was converted with lithium dimethylcopper and acetic anhydride to (139). Subjection of (139) to dehydrogenation, hydrolysis and methylation, respectively, yielded (140) which was converted to tetralone (141) by reduction, hydrolysis and methylation of pyralidine enamine. Alkylation of (141) with 2-... 

Alkylation of cyclohexanone enamines with methyl chloro(methoxy)acetate, followed by alkaline hydrolysis, affords the y-keto acid 30, which readily cyclizes to the unsaturated lactone 31 on treatment with hydrogen chloride in acetic acid (equation 20)40. 

Methyl jasmonate (218) has a //arris-locked, 2,3-disubstituted cyclopentanone structure.297 The synthetic route devised by Sisido and co-workers, outlined in Scheme 34, is direct and requires no isomer separation.298) Reaction of the pyrrolidine enamine of methyl 2-oxycyclopent-l-yl acetate (214) with 3-bromo-2-penta-none in toluene gave 215 after hydrolysis. An intramolecular aldol condensation afforded 216 (note double bond migration) whose epoxidation followed by treat-... 

Other functional polyfluorinated compounds are available by addition of perhaloalkyl halides to enol derivatives, e.g. formation of 1 and 2 (see also Table 4). The adducts formed from enol acetates or enol ethers are not very stable and their hydrolysis to give a-perhaloalkyl aldehydes or ketones is often rapid. However, the enol derivatives can be transformed either to give ketals using alcohols or to give various products by oxidation and reduction reactions. The peculiar perfluoroalkyl iodide addition to enamines is spontaneous at room temperature, e.g. formation of 3. ... 

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