Acyl piperidine

As noted earlier (see Chapter 10), 4-acyl piperidines separated from benzimidazole by a three carbon chain often show antipsychotic activity. The heterocycle can apparently be replaced by a pyridopyrimidine ring. Thus alkylation of piperidine 41 with halide 42 affords pirenperone (43). ... 

Anodic methoxylation of conformation-ally biased 2-substituted At-acyl piperidines leads regioselectively to 6-methoxy products owing to the steric constraints... 

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (41 X = NH) the a carbon signal is shifted by about 20 ppm, to ca. 8 47.7, while in yV-methylpiperidine (41 X=NMe) it appears at 8 56.7. Quatemization at nitrogen produces further effects similar to replacement of NH by Aralkyl, but simple protonation has only a small effect. W-Acylpiperidines (41, X = NCOR) show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 ppm, and the mean shift is close to that of the unsubstituted amine (41 X = NH). The nitroso compound (41 X = N-NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 ppm). The (3 and y carbon atoms of piperidines, W acyl piperidines and piperidinium salts are all upheld of the cyclohexane resonance, by 0-7 ppm. 

Controlled oxidation of A-acyl-piperidines and -pyrrolidines can be used to prepare 2-alkoxy derivatives or the equivalent enamides, which are useful general synthetic intermediates. The former are susceptible to nucleophilic substitution under Lewis-acid catalysis, via Mannich-type intermediates, and the latter can undergo electrophilic substitution at C-3 or addition to the double bond. 

Enol phosphates derived from iV-acyl-piperidin-2-one (or 2-oxoazepane) can be utilized in cross-coupling... 

Under these conditions, the formation of higher esters of sucrose is favoured so that, even in the presence of an excess of sucrose, the product will contain 10% or more of the diester. In practice this rarely is a disadvantage. Other solvents (dimethyl-sulphoxide, pyridine, N-acyl piperidine, etc.) cuid catalysts can be used, but the separation and purification of the sucrose ester still is costly. 

Acylated piperidines force ( -substituents into axial confomnation... 

Propiophenone is the product of F.-C. acylation piperidine is available by reduction of pyridine as a cheap commodity. 

Ujjainwalla F, Chu L, Goulet MT, Lee B, Warner D, Wyvratt MJ, inventors Merck Co. Inc., assignee. Acylated piperidine derivatives as melanocortin-4 receptor agonists. WO/ 2002/068388,2002 Sep 06. 

A -Piperideine — see Pyridine, 2,3,4,5-tetrahydro-A -Piperideine — see Pyridine, 1,2,3,4-tetrahydro-A -Piperideine — see I ridine, 1,2,3,6-tetrahydro-Piperideines — see Pyridines, tetrahydro-Piperidine, 1-acryIoyI-polymers, 1, 284 Piperidine, JV-acyl-... 

The results of more recent investigations by Blicke with Maxwell and with Kaplan covering a wide range of basic components and of acyl residues, do not lend themselves to a simple generalisation. The basic components were mainly dialkylamino-derivatives of aliphatic hydrocarbons from ethane to pentane, e.g.,. CHj. CHj. NMcj to. CHj. CMcj. CHj. NEtj, and similar but shorter series of derivatives of piperidine (CgHjoN), morpholine, e.g.,. CHj. CHj. NC HgO, and methylcj/clohexylamine... 

Experimental evidence, obtained in protonation (3,6), acylation (1,4), and alkylation (1,4,7-9) reactions, always indicates a concurrence between electrophilic attack on the nitrogen atom and the -carbon atom in the enamine. Concerning the nucleophilic reactivity of the j3-carbon atom in enamines, Opitz and Griesinger (10) observed, in a study of salt formation, the following series of reactivities of the amine and carbonyl components pyrrolidine and hexamethylene imine s> piperidine > morpholine > cthyl-butylamine cyclopentanone s> cycloheptanone cyclooctanone > cyclohexanone monosubstituted acetaldehyde > disubstituted acetaldehyde. 

A,A-Diacetyl-2-trifluoromethylaniline, organic solvents, 3-24 h, rt or reflux, 54-99% yield. Acylation selectivity is a very sensitive function of steric effects this reagent selectively acylates pyrrolidine over piperidine (15 1). It is more selective than the diacetylaminoquinazolinones. ... 

Amidoalkylation of silyl enol ethers with /V-acyliiiiiiiium ions containing camphanoyl-derived acyl functions (see Appendix) as the chiral auxiliary leads to optically active 2-substituted piperidine derivatives with moderate to high diastereoselectivity, depending on the chiral auxiliary and the cnol ether82 99. The auxiliary is removed by hydrolysis with base or acid. 

Neier and coworkers have shown that piperidine diones (e.g., 105) can be prepared stereoselectively using a cascade Diels-Alder/acylation reaction of ketene acetal 104 <96T(52)11643>. 

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