Asher Mandelbaum

Preparative separation of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids by pH-zone-refining counter-current chromatography

The application of pH-zone-refining counter-current chromatography (CCC) to the preparative separation of stereoisomeric acids is described. The separation was accomplished on the basis of the difference in acidity of the two stereoisomers. pH-Zone-refining CCC of 400 mg of a crude synthetic mixture of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids yielded 49.5 and 40 mg of the pure Z- and E-stereoisomers respectively. The two-phase solvent system consisted of hexane-ethyl acetate-methanol-water (1:1:1:1). Trifluoro acetic and octanoic acids were used as retainer acids. The eluent base was aqueous ammonia. The eluted fraction were monitored by gas chromatography-mass spectrometry.

Intramolecular proton transfers in stereoisomeric gas-phase ions and the kinetic nature of the protonation process upon chemical ionization

The isobutane chemical ionization (CI) mass spectra of cis- and trans-1-butyl-3- and -4-dimethylaminocyclohexanols and of their methyl ethers exhibit abundant [MH - H(2)O](+) and [MH - MeOH](+) ions respectively. On the other hand, only the MH(+) ions of the cis-isomers exhibit significant [MH - H(2)O](+) and [MH - MeOH](+) ions under collision-induced dissociation (CID) conditions. The non-occurrence of water and methanol elimination in the CID spectra of the trans-isomers indicates retention of the external proton at the dimethylamino group in the MH(+) ions that survive after leaving the ion source and the first quadrupole of the triple-stage quadrupole ion separating system, and the trans-orientation of the two basic sites does not allow proton transfer from the dimethylamino group to the hydroxyl or methoxyl. Such transfer is allowed in the cis-amino alcohols and amino ethers via internal hydrogen-bonded (proton-bridged) structures, resulting in the elimination of water and methanol from the surviving MH(+) ions of these particular stereoisomers upon CID. The abundant [MH - ROH](+) ions in the isobutane-CI mass spectra of the trans-isomers indicates protonation at both basic sites, affording two isomeric MH(+) ions in each case, one protonated at the dimethylamino group and the other at the less basic oxygen function. These results show that the isobutane-CI protonation of the amino ethers and amino alcohols is a kinetically controlled process, occurring competitively at both basic sites of the molecules, despite the large difference between their proton affinities ( approximately 25 and approximately 35 kcal mol(-1); 1 kcal = 4.184 kJ). Copyright 1999 John Wiley & Sons, Ltd.

Chemistry and stereochemistry of benzyl-benzyl interactions in MH+ ions of dibenzyl esters upon chemical ionization and collision-induced dissociation conditions

Isobutane chemical ionization mass spectra of dibenzyl esters of a wide variety of aliphatic, olefinic, alicyclic and aromatic dicarboxylic acids exhibit abundant m/z 181 C 14 H + 13 ions, indicating a highly general rearrangement process involving the formation of a new bond between the two benzyl groups. An extensive collision-induced dissociation and deuterium labeling study suggested that these ions are an almost equimolar mixture of isomeric α-o-tolylbenzyl, α-p-tolylhenzyJ and p-benzylbenzyl cation structures, and this composition is identical for all the diesters examined. This structural assignment of the C 14 H 13 + ions suggests a mechanistic pathway for their generation, based on the formation of the new bond between the benzyl methylene group of the protonated benzoxycarb-onyl and the phenyl ring of the other ester moiety via π- (and/or ion-neutral) and α-complexe. Stereoisomeric diesters show an unusual steric effect: trans-isomers give rise to much more abundant C 14 H + 13 ions than the cis counterparts. This behavior is explained by stabilized proton-bridged structures of the MH+ ions of the cis-isomers.

Constituents of Catha edulis : Isolation and structure of cathidine D

Abstract Work which has recently appeared on the structures of Celastraceae alkaloids in addition to physical and chemical evidence adduced with respect to cathidine D permits formulation of structure 7a or 7b for this component of Catha edulis .

Stereochemistry of retro-diel-salder fragmentation in gas-phase ions formed by chemical ionization

Abstract Retro Diels Alder fragmentation is highly stereospecific in the diones 1 under chemical ionization conditions, both with methane and isobutane as the reagent gases. Only the cis -isomers yield abundant protonated diene and quinone ions. The isotope effect indicates preferential protonation on a CO oxygen, and a subsequent H-migration prior to the formation of the protonated diene cations in the cis isomers.

The role of hydrogen migration in the mechanism of alcohol elimination from MH+ ions of ethers upon chemical ionization

An enhanced elimination of alcohol under isobutane Cl conditions, resulting in highly abundant [MH - ROH] + ions, has been observed in several primary and secondary ethers having a tertiary β-position (methine), as compared with those with β-methylene. This elimination exhibits a significant degree of stereospecificity in stereoisomeric 2-methyl-1-methoxycyclohexanes 4 and 1-methoxy-trans-decalins 7, affording more abundant [MH - ROH] + ions in the cis isomers 4c and 7tc than in their trans counterparts 4t and 7tt. These findings suggest involvement of a 1,2-hydride migration from the β- to α-position in the course of the alcohol elimination from the MH + ions of the above cis-ethers, resulting in tertiary carbocation structures. The proposed mechanism of alcohol elimination is supported by a considerable deuterium isotope effect detected in β-deuterium-labeled cis-2-methyl-1-methoxycyclohexane and by a CID study of the structures of [MH - ROH] + ions obtained from cis- and trans-1,2-dialkoxycyclohexanes. Ring contraction by a Meerwein-type rearrangement has also been observed in the latter system.

The role of hydride migration in the mechanism of alcohol elimination from protonated ethers upon chemical ionization Experiment and theory

An enhanced elimination of methanol under isobutane-chemical ionization (CI) conditions, resulting in highly abundant [MH–CH3OH] + ions, has been observed in several primary and secondary methyl ethers having a tertiary -position (methine), as compared with those with -methylene. This elimination is stereospecific in stereoisomeric 2-methyl-1-methoxycyclohexanes and in other ethers affording significantly more abundant [MH–CH 3OH] + ions in the cis-isomers than in their trans-counterparts. These findings suggest involvement of a 1,2-hydride migration from the -t o-position in the course of the alcohol elimination from the MH + ions of the above cis-ethers, resulting in stabilized tertiary carbocation structures. The possible pathways of methanol elimination from protonated cis-2-methyl-1-methoxycyclohexane were explored by density functional calculations at the B3LYP/6-31+G(d,p) level of theory. The transition states for MeOH elimination involving 1,2-hydride migration were located and the activation energy of the process was evaluated. The activation barrier of the alcohol elimination assisted by 1,2-hydride migration is lower by ∼10 kcal/mol than the simple bond cleavage (9.6 kcal/mol vs. 20.5 kcal/mol). These computational results support the mechanistic pathway involving the 1,2-hydride transfer. A step-wise mechanistic pathway is proposed for the less efficient elimination of methanol from protonated trans-2-methyl-1methoxycyclohexane.

Boron trifluoride-catalyzed rearrangements of some tetrasubstituted neotriterpene epoxides—II: Hopene-II oxide and its analogue in the A:B-neoallobetulin series

Abstract While hopene-II oxide is converted by HCl into the 11,13(18)-diene, it rearranges quantitatively under the action of BF3-ether complex to the 19(18 → 13)-abeo-18-oxo derivative. The structurally similar 9,10β:19β, 28-diepoxy-A:B-neo-18β-oleanane, prepared from allobetulin, behaves in an entirely analogous manner.

Boron trifluoride-catalysed rearrangements of some tetrasubstituted neotriterpene epoxides—I

Abstract The treatment of A′-neogammacer-17(21)-ene oxide ( 1a ) with BF 3 ·Et 2 O complex in CHCl 3 produces entirely different results from those obtained when the same epoxide is treated with HCl in EtOH: while the protic acid converts the compound into the 15,17(21)-diene ( 2a ), the Lewis acid produces rearrangements in the carbon skeleton, with formation of the 28-nor-21α-methyl-12,17-diene ( 3a ) and of the 22,29,30-trisnor-17α-isopropyl-21-one ( 4a ). The structurally similar 19β,28-epoxy-A-neo-18α-olean-3(5)-ene oxide ( 1b ) behaves in a completely analogous manner.

Steric hindrance and the kinetic nature of the protonation process in 4-amino-1-methoxycyclohexanes upon chemical ionization

The abundant [MH – MeOH]+ ions in the isobutane-chemical ionization (CI) mass spectra of trans-4-amino-1-methoxycyclohexanes (where proton transfer between the two sites does not take place, in contrast to the cis-isomers) indicate protonation at the two basic sites, affording two isomeric MH+ ions in each case, one protonated at the dimethylamino group, MH+(N), and the other at the less basic oxygen function, MH+(O). This result shows that the isobutane-CI protonation of the aminoethers is a kinetically controlled process, occurring competitively at both basic sites (despite the large difference between their proton affinities, ∼105–145 kJ mol−1), and the ion abundance ratio [MH+] / [MH – MeOH]+ reflects the ratio of abundances of the isomeric MH+ ions, MH+(N) and MH+(O), initially protonated at one of the two sites. The latter ion abundance ratio decreases with the bulkiness of the N-substituents (by a factor of more than 10 between N,N-dimethyl- and N,N-diisopropyl-derivatives), indicating lower rates of protonation at the amino group when the approach of the protonating reagent (C4H9+ ion in our measurements) to the nitrogen atom is increasingly hindered by the N-substituents. Another effect of steric hindrance in the CI process involves enhanced formation of the molecular radical cations M+• (presumably by a charge exchange mechanism), in competition with the usual protonation, in aminoethers with bulky N-substituents.