Antihydrophobic cosolvent effects for alkylation reactions in water solution, particularly oxygen versus carbon alkylations of phenoxide ions.
Antihydrophobic cosolvents such as ethanol increase the solubility of hydrophobic molecules in water, and they also affect the rates of reactions involving hydrophobic surfaces. In simple reactions of hydrocarbons, such as the Diels-Alder dimerization of 1,3-cyclopentadiene, the rate and solubility data directly reflect the geometry of the transition state, in which some hydrophobic surface becomes hidden. In reactions involving polar groups, such as alkylations of phenoxide ions or S(N)1 ionizations of alkyl halides, cosolvents in water can have other effects as well. However, solvation of hydrophobic surfaces is still important. By the use of structure-reactivity relationships, and comparing the effects of ethanol and DMSO as solvents, it has been possible to sort out these effects. The conclusions are reinforced by an ab initio computer model for hydrophobic solvation. The result is a sensible transition state for phenoxide ion as a nucleophile, using its oxygen n electrons to avoid loss of conjugation. The geometry of alkylation of aniline is very different, involving packing (stacking) of the aniline ring onto the phenyl ring of a benzyl group in the benzylation reaction. The alkylation of phenoxide ions by benzylic chlorides can occur both at the phenoxide oxygen and on ortho and para positions of the ring. Carbon alkylation occurs in water, but not in nonpolar organic solvents, and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para. The effects of phenol substituents and of antihydrophobic cosolvents on the rates of the competing alkylation processes indicate that in water the carbon alkylation involves a transition state with hydrophobic packing of the benzyl group onto the phenol ring. The results also support our conclusion that oxygen alkylation uses the n electrons of the phenoxide oxygen as the nucleophile and does not have hydrophobic overlap in the transition state. The mechanisms and explanations for competing oxygen and carbon alkylations differ from previous proposals by others.
Breslow
Ronald
R
Department of Chemistry, Columbia University, New York, New York 10027, USA. rb33@columbia.edu
Groves
Kevin
K
Mayer
M Uljana
MU
D000478:Alkylation; D002244:Carbon / Q000737:chemistry*; D003517:Cyclopentanes / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D012996:Solutions; D014867:Water / Q000737:chemistry*
D003517:Cyclopentanes; D010636:Phenols; D012996:Solutions; D014867:Water; C042329:phenoxy radical; D000431:Ethanol; C004709:1,3-cyclopentadiene; D002244:Carbon; D010100:Oxygen; D004121:Dimethyl Sulfoxide