Piperidine, A -methyl

Dehydrogenation of himbacine with palladium-charcoal at 260° furnished dehydrohimbacine (V). That the transformation involved the saturation of the double bond and the conversion of an A -methyl-piperidine system into a pyridine derivative was apparent from the elemental analysis of the product, its UV-spectrum 265 mp, log 3.65), and the marked change in p/v from 9.3 to 5.4 (50% ethanol). Compound V was also obtained from dihydrohimbacine under the same conditions. 

The modified Oppenauer oxidation was used in the synthesis of estrone by P. Kocovsiw et al. The tetracyclic did was exposed to aluminum isopropoxide and A/-methyl-piperidine-4-one (oxidizing agent) to obtain the corresponding enone in good yield. The formation of the enone involved the migration of the initial p,y-double bond. The treatment of this enone with TsOH overnight in ether led to the formation of estrone by aromatization. 

The conformational behavior of A-methyl-piperidine (6) had been extensively studied. Most researchers now agree that the Me-equatorial conformer is favored by about... 

The commercially available diethyl azadicarboxylate like reagents are listed below. DEAD (4) and DIAD (5) are by far the most frequently used. The methyl (6), benzyl (7) and terr-butyl (8) analogs of the most commonly used reagents are also known, but used much less frequently. Bis-(2,2,2-trichloroethyl)azadicarboxylate, another commercially available compound, has also been reported, but applications thereof appear to be very limited. ADDP, l,r-(azodicarbonyl)-dipiperidine (10), was first reported by Tsunoda. This reagent appears be useful for more difficult Mitsunobu reactions related reagents in which the piperidine moiety has been replaced by morpholine or A-methyl piperazine are also known. These reagents and the reduced hydrazine products thereof can often be precipitated out by the addition of hexanes to Ae reaction mixture additionally, treatment with mild acid can be useful in the removal of the A-methyl piperidine reagent. 

Also, 4-dimethylaminopyridine (4-DMAP) as a ligand was quite effective, whereas pyridine, A/ -methyl-piperidine, or EtjN induced only isomerization of the double bond into the interior of the substrate. A catalyst derived from the... 

In cyclic amines, such as the protonated form of 3-fluoro-A -methyl-piperidine (21), these interactions provide significant conformational bias [53-55]. In 21, the ring F atom strongly prefers an axial disposition despite experiencing steric compression, with the calculated conformer populations provided in Fig. 6 [55]. As the global minimum, conformer A dominates to the extent of 95-96 %, stabilized by an electrostatic interaction between the F and NH+ moieties, whilst conformer D contributes 4-5 % at equilibrium with the unfavorable diaxial interactions compensated by a productive electrostatic effect. 

If, however, the /7-nitrophenyl ester of iV-henzoyl-L-leucine is treated with 1-methyl-piperidine in chloroform for 30 min and then coupled with glycine ethyl ester, the dipeptide isolated is almost completely racemic. Furthermore, treatment of the p-nitrophenyl ester of iV-benzoyl-L-leucine with 1-methylpiperidine alone leads to the formation of a crystalline material, C13H15NO2, having strong IR bands at 1832 and 1664 cm . Explain these observations, and suggest a reasonable stmcture for the crystalline product. 

The para direct deactivation (toward excess piperidine, 45°) by a 4-methyl substituent on 2-nitrobromobenzene (164) is greater than para indirect deactivation by a 5-methyl group (rate of displacement equivalent to absence of a methyl group). A similar result was obtained with 2-nitrochlorobenzenes substituted by methyl or methoxy groups in the reaction with piperidine in benzene. 

Ethyl Bromide 4-Chloro-1-methyl piperidine Dlbenzo[a,e] cycloheptatrlen-5-one Hydrogen chloride... 

The TS preference is influenced by avoidance of A1,3 strain between the a-methyl group and the piperidine ring. 

Figure 4.4 Stereospecific esterification synthesis of (/t)-/V-(fe/V-hutoxycarbonyl)-3-hydroxyinethyl-piperidine from (7 ,5)-A,-(/< r7-butoxycarhonyl)-3-hydroxy methyl piperidine applying a sequence of stirred-tank reactor, extraction module, second stirred-tank reactor and second extraction module... 

Figure 4. (a) Selected residues from the combining site of antibody 5C8 com-plexed to piperidine-A/-oxide hapten 4, as determined by X-ray crystallography.1151 The linker portion of the hapten has been truncated to a methyl for comparison with the theozyme complex, (b) The formate/formic acid theozyme complexed to the model of hapten 4, as optimized through quantum mechanical calculations.161... 

FIGURE 8.15 Alkylamines encountered in peptide synthesis. 1, pyridine 2, 2,4,6-trimethylpy-ridine 3, 2,6-di-ferf-butyl-4-methylpyridine 4, 4-dimethylaminopyridine 5, A-methyl-morpholine, 6, fV-methylpiperidine 7, triethylamine 8, diisopropylethylamine 9, l-diethylaminopropane-2-ol 10, dicyclohexylamine 11, diethylamine 12, piperidine 13, piperazine 14, morpholine 15, l,8-diazabicyclo[5.4.0]undec-7-ene 16, 4-(aminoethyl)piperidine 17, frw(2-aminoethyl)amine 18, 3-dimethylaminopropylamine 19, methylamine 20, dimethy-laminoethane-2-ol 21, 1,2,2,6,6-pentamethylpiperidine 22, l,4-diazabicyclo[2,2,2]octane 23, 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5 -ene. 

Figure 2.2 Three piperidine alkaloid teratogens from Conium maculatum (poison-hemlock) (a) coniine, (b) y-coniceine, and (c) A-methyl coniine, with accompanying LD50 as determined in a mouse bioassay.

Figure 2. Solid-state spectra of four different epoxies (hosed on the resin diglycidyl ether of bisphenol-A) are compared with the liquid-state spectra of their respective unreacted components, The chemical compositions are in Table I. Here the epoxies are identified by their main curing agent (a) PIP—piperidine (b) MPDA—metaphenylene diamine (c) HHPA—hexahydro-phthalic anhydride (d) NMA—nadic methyl anhydride.

Lithio-Af-methylpiperidines and -pyrrolidines are chemically and configurationally stable for at least 45 min at —40 °C in THF/TMEDA. Structural studies in THF showed that the piperidine is a bridged monomer in both racemic and enantiopure form, whereas the pyrrolidine is a homochiral dimer in both enantiopure and racemic forms. The difference in aggregation state does not appreciably affect the temperatures at which racemization is avoided. These A-methyl heterocycles are considerably more robust than the... 

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