PMID- 11052075
OWN - NLM
STAT- MEDLINE
DCOM- 20001128
LR  - 20190710
IS  - 0022-3263 (Print)
IS  - 0022-3263 (Linking)
VI  - 65
IP  - 20
DP  - 2000 Oct 6
TI  - Eight-membered-ring solid-state conformational interconversion via the atom-flip 
      mechanism, a CPMAS 13C NMR and crystallographic stereochemical study.
PG  - 6345-53
AB  - Nefopam methohalide (chloride, bromide, and iodide) medium-ring quaternary 
      ammonium salts of the non-narcotic analgesic tertiary amine drug give crystals 
      belonging to the identical monoclinic P2(1)/c space group, and all of these 
      pseudopolymorphs exhibit the same packing motif. A singular boat-boat (BB) more 
      compact conformation is observed in the nefopam methochloride crystal. Larger 
      halide anions (bromide and iodide) increase the void distance between the 
      2(1)-screw axis related adjacent ammonium cations to accommodate void-size 
      dependent equilibrium quantities of the twist-chair-chair (TCC) more extended 
      conformation. The BB:TCC occupancy factors are 0.961(5):0.039(5) [193 K], 
      0.780(5):0.220(5) [293 K], and 0.755(6):0.245(6) [343 K] for the methobromide 
      crystal, while values of 0.657(5):0.343(5) [193 K] and 0.592(7):0.408(7) [293 K] 
      were measured for the methiodide. Above a minimum of ca. 2.53 A, the occupancy 
      factors were found to be linearly correlated to the intermolecular 
      (TCC)Me(eq)-H...H-Me(ax)(TCC) distance between abutting methyl group protons in 
      2(1)-screw axis related neighbors. Temperature-dependent occupancy factors for 
      the two conformers are interpreted in terms of a medium ring atom-flip facile 
      interconversion between the two low energy conformations in crystals containing 
      the appropriate size intercation void. A BB/TCC atom-flip interconversion in the 
      methochloride unit cell would result in van der Waals interactions due to an 
      estimated 2.31 A close intermolecular (TCC)Me(eq)-H...H-Me(ax)(TCC) distance 
      between adjacent 2(1)-screw symmetry ammonium cations. The 203 K low-temperature 
      CPMAS 13C NMR spectrum of the methiodide salt showed two slow exchange limit 
      (SEL) delta 57.91 [BB] and delta 63.10 [TCC] OCH2CH2N peaks. A variable 
      low-temperature CPMAS NMR investigation of the solid methiodide showed complex 
      dynamic behavior that cannot be interpreted solely on the basis of an atom-flip 
      conformational interconversion. Local magnetic fields from the gem-dimethyl 
      rapidly rotating proton magnetic dipoles provide a distance-dependent T1 
      relaxation mechanism for neighboring carbons in the solid-state.
FAU - Glaser, R
AU  - Glaser R
AD  - Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 
      glaser@bgumail.bgu.ac.il
FAU - Novoselsky, A
AU  - Novoselsky A
FAU - Shiftan, D
AU  - Shiftan D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Org Chem
JT  - The Journal of organic chemistry
JID - 2985193R
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 4UP8060B7J (Nefopam)
SB  - IM
MH  - Analgesics, Non-Narcotic/*chemistry
MH  - Crystallography, X-Ray
MH  - Magnetic Resonance Spectroscopy
MH  - Molecular Conformation
MH  - Nefopam/*chemistry
MH  - Quaternary Ammonium Compounds/*chemistry
EDAT- 2000/10/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/29 11:00
PHST- 2000/10/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/29 11:00 [entrez]
AID - 10.1021/jo000146g [doi]
PST - ppublish
SO  - J Org Chem. 2000 Oct 6;65(20):6345-53. doi: 10.1021/jo000146g.