A -methylpiperidine

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 (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

FMF Chen, Y Lee, R Steinauer, NL Benoiton. Mixed anhydrides in peptide synthesis. Reduction of urethane formation and racemization using A-methylpiperidine as tertiary amine base. J Org Chem 48, 2939, 1983. 

The high-pressure reaction of A-methylpiperidine with 4-chloronitrobenzene yields A-(4-nitrophenyl)piperidine (equation 117) 2-chloronitrobenzene and chloro-2,4-dinitrobenzene behave analogously. A-Methylpyrrolidine and 4-chloronitrobenzene afford a mixture of A-(4-nitrophenyl)pyrrolidine and the product 342 of ring scission (equation 118)385. 

Although there is a kinetic barrier to the direct deprotonation of tertiary amines, Ahlbrecht and Dollinger showed in 1984 that the Schlosser superbase, i c-BuLi/f-BuOK, can deprotonate A-methylpiperidine selectively on the methyl group (Scheme 3). This superbase probably yields an a-amino-organopotassium species (and f-BuOLi), but treatment with LiBr effects transmetalation to the more nucleophilic, and less basic, a-amino-organolithium species. Electrophilic quench with several aldehydes and ketones gives substitution products in good yields as typified by the example in Scheme 3. Similarly,... 

Alkylation of pyrrohdine and piperidine heterocycles was investigated extensively by Gawley and coworkers. The initial evaluation of 2-lithio-A-methylpiperidine and 2-lithio-A-methylpyrrolidine as nucleophiles was conducted on racemic material, but... 

Recently, both enantiomers each of cis- and tran5 -5-butyl-2-heptylpyrrolidine (10c) have been synthesized from glutamic acid by an excellent method with high diastereomeric and enantiomeric purity (417). The thiolactam (293) prepared from L-glutamic acid was reacted with benzyl 2-(trifluoromethylsul-fonyloxy)oetanoate to yield the rather unstable salt (294), which without purification was treated with triphenylphosphine and A-methylpiperidine to afford... 

Hydrolysis of the ethyl ester proceeded smoothly using hydrochloric acid in acetic acid to give carboxylic acid 69 in 88% yield (Scheme 4.9). Previously, amines were allowed to react with the carboxylic acid core in hot DMSO to deliver the C7 products however, the difluoroborate 70, derived from the carboxylic acid 69, greatly increased the reactivity of the C7 position. Consequently, the displacement of the C7-F with amines was accomplished at lower temperature (Baker et al., 2004 Cecchetti et al., 1996 Domalaga et al., 1993 Ellsworth et al., 2005a,b Hu et al., 2003). In this event, the carboxylic acid was allowed to react with boron trifluoride to deliver difluroboronate 70 in excellent yield. The thus afforded borate ester reacted with A -methylpiperidine in DMSO in the presence of triethylamine at ambient temperature to furnish ( —)-ofloxacin (1, levofloxacin) in 56% yield. 

Furthermore, thianthrene react with 2-diazo(fluoroalkyl)acetoacetates under mild conditions in the presence of catalytic Rh2(OAc)4 to afford the corresponding sulfonium ylides as the major products <2004JFC(125)1071>. In addition to all the desulfurization conditions reported in CHEC-II(1996) <1996CHEC-II(6)447>, a new efficient reagent was developed. Introduction of the sodium salt of 3-hydroxy-A-methylpiperidine into the aggregates of NiCRA s (NaH-RONa-NiX2) led to 83% yield of desulfurized thianthrene in 30 min <1998TL8987>. 

Die Molarpolarisation der Komplexe des A-Methylpiperidins hangt in einem groBen MaBe von der Starke der sauren Komponente ab, wie das aus der Tab. II zu sehen ist. Die abhangigkeit zwischen P, eventuell AP und pK kann man angenahert als eine Gerade darstellen. 

The values given in Table XI (Section III,A,1) for the A-methylpiperidine equilibria show that dipole-moment measurements with the associated assumptions consistently give rise to lower estimates of — AG° than those from other methods. 

Measurements of the Bohlmann bands in piperidine derivatives139,140 have supported a preference for /V-Hcq in the piperidine equilibrium. The IR spectra of 2,6-dideuterated piperidine, A-methylpiperidine, and A-isopro-pylpiperidine showed two C—D absorptions at 2075-2030 cm-1 (anti-C—D... 

Photoelectron spectra and STO-3G calculations on methylpiperidines show that equatorial methyl substituents at the 2-, 3-, and 4-positions lower the ionization potential of the nitrogen lone pair by <0.1 eV. An axial methyl at C-2, however, lowers the ionization potential by 0.26 eV. These influences on ionization potentials are nearly identical in both piperidines and A-methylpiperidines, indicating that the lone-pair orientations in both systems are similar. The STO-3G calculations indicate a favoring of the equatorial A-H conformation of the piperidines by 1.0—1.9 kcal mol-1.174... 

Aryl)thioindoxyls undergo both C- (in the 2-position) and O-alkylation in the presence of potassium terf-butoxide.609 The C-alkylated products (237) react with A-methylpiperidine-4-magnesium chloride to give compounds (238) (as mixtures of a- and /3-racemates), which lose water on treatment with hydrogen bromide to give 239. 

As expected, macroscale reduction gave products corresponding to those from reduction of the parent pyridine, that is, piperideines and piperidines. Electrolysis of a series of N-alkyl-substituted 2-pyridones, for example N-methyl-(79), yielded a mixture of A-methylpiperidine and -piperideine 80.126 Reduction of the methyl ether of 2-pyridone gave piperidine only.127... 

The conformational equilibrium of A-methylpiperidine-m-2,6-fif2 favors conformer 40 with both deuteriums equatorial, with an equilibrium constant of 1.23.110 To the extent that the conformational preference in the protonated amine is much smaller and can be neglected, this IE also corresponds to a greater basicity of the conformer 41 with the deuteriums axial. Similarly the preferences of 3-azabicyclo[3.2.2]nonanes and (PhCHD)3N for conformers with H anti to the nitrogen lone pair implies a lower basicity for those conformers.111,112... 

Intermolecular insertion of alkenes to a-allyl intermediates is possible with an Ru catalyst. For example, 3,5-dienecarboxamide 274 is formed in high yield by Ru(cod)(cot)-catalysed coupling of 2-butenyl methyl carbonate (273) with acrylamide in the presence of A-methylpiperidine [122], Ni-catalysed transformation of allyl 3-butenoate (275) to heptadienoic acids 276a and 276b proceeds by insertion of the double bond to 7r-allylnickel intermediate [123],... 

AF-DX 116, 1 l-( 2-[(Diethylamino)methyl]-l-piperidinyl acetyl)-5,l l-dihydro-6//-pyrido-[2,3-/i]( l, 4)benzodiaz-epin-6-one DAG, Diacylglycerol IP3, Inositol trisphosphate 4-DAMP, 4-Diphenylacetoxy-A-methylpiperidine HHSD, Hexahydrosiladifenidol ... 

A -Methylpiperidine is a tertiary amine, and as such it is oxidized by mercuric acetate to 1-methyl-1,4,5,6-tetrahydropyridine. 

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