Chair conformation piperidine

The structure analysis of the piperidine derivatives and its drugs in the protein showed that the -substitutions are invariably positioned in the anticlinal orientation irrespective of the different substitutions in the rings and the non-covalent interactions. The bulky groups are in a equatorial orientation in the chair conformation (piperidine ring) and assumes opposite orientations in the boat and twist-boat conformations. Since the number of drug molecules analyzed here are very small, no significant conclusion could be reached concerning the confermers. 

X-Ray diffraction analyses of vincristine methiodide (39) and vinzoli-dine 1-naphthalene sulfonate (40) provide atomic coordinates of compounds that are either modified in the velbanamine portion (alkylation at N-6, Fig. 3) or in the vindoline portion (a spiro-fused oxazolidinedione at C-3 and C-23, Fig. 4). These structures show a chair-boat conformation for ring C with C-8 exhibiting an endo pucker. Ring D is clearly in a chair conformation, but, in contrast to the conclusions drawn from C-NMR studies, the N-6 -C-7 bond is axial relative to the piperidine ring. 

A (i) The fer/-buiyl group is sufficiently bulky that it can only be accommodated in an equatorial site in piperidine. As a result, the ring is locked in a single chair conformation ... 

Distortion of the chair conformation by substitution occurs in 2,2,6,6-tetramethyl-piperidin-4-one hydrochloride (45) (71AX(B)932), in which steric interaction between axial methyl groups leads to flattening of the ring. The resultant C(2)—C(6) intramolecular distance is 3.2 A, to be contrasted with 2.4 A in the non-methylated compound. A similar effect is to be found in other 2,2,6,6-tetramethyl derivatives (81AX(B)1771). In the related free radical nitroxide (46) the steric interactions are reduced by adoption of a symmetric twist chair form (74AX(B)790). 4-Chloro-5-methylamino-2,3,6-pyridinetrione monohydrate... 

The shapes of heterocyclic rings are very much like those of their all-carbon analogs. Thus, six-membered heterocycles such as piperidine exist in a chair conformation analogous to cyclohexane. 

A stereoselective 6-exo selenoamination to form a tetrahydroisoquinoline ring system is probably a result of the specific substitution pattern.252 Selenocyclizations which generate piperidine systems by 6-endo cyclization give products predicted by reaction through the more stable chair conformation (equation 116).41 158c 216e,232a... 

Otherwise, the piperidine ring system was considered to be in the stable chair conformation. The two different experimental barriers to ring inversion and N-inversion of N-methylpiperidine were reconsidered. An accurate line shape analysis of the dynamic NMR spectra in the gas phase... 

The X-ray structure of l-piperidino-2,4-dinitrobenzene was published (95MI801). The piperidine ring exhibits a slightly distorted chair conformation the N-atom is almost in a plane due to the partial C,N double bond, and the aromatic ring shows a slight boat deformation with the o/p-nitro groups twisted out of plane. UV and NMR data indicate that the molecule in solution presents a conformation similar to that in the solid state. In the crystalline anhydrous N-methylpiperidine betaine 86 (cf. Scheme 33) the piperidine ring adopts the usual chair conformation... 

Piperidino)valeric acid 88 adopts the chair conformation with the substituent in an equatorial conformation (99JMS125) as does 1-[1-(1-phenylethyl)cyclohexyl]piperidine 89 (91AX(C)223) but occupying the axial site of the cyclohexane ring (cf. Scheme 34). 

The structure of (—)-morphine was established conclusively 10 by X-ray crystallography from two projections of the hydroiodide dihydrate salt and confirmed for codeine and morphine by an X-ray study of their hydrochloride trihydrate salts/111 The piperidine ring was shown to adopt a chair conformation with the N-Me equatorial. The absolute stereochemistry of morphine was also confirmed by X-ray studies/415"417 ... 

The stereochemistry of an isomer of 6,7,8,8a-tetrahydro-2-phenyl-5//-oxazolo[3,2-fl]pyridin-3[2//]one has been established by X-ray analysis, and the piperidine ring has been shown to adopt a chair conformation. The published bond lengths are given in 306 (77CSC553). 

---