Worked Example 13.1 Predicting the Relative Acidity of a Substituted Phenol Strategy ldentify the substituent on the aromatic ring Decide whether it is electron-donating or electron- withdrawing -Electron-withdrawing substituents make the phenol more acidic by stabilizing the phenoxide anion -Electron-donating substituents make the phenol less acidic by destabilizing the phenoxide anion
Strategy ▪ Identify the substituent on the aromatic ring ▪ Decide whether it is electron-donating or electronwithdrawing ▪ Electron-withdrawing substituents make the phenol more acidic by stabilizing the phenoxide anion ▪ Electron-donating substituents make the phenol less acidic by destabilizing the phenoxide anion Worked Example 13.1 Predicting the Relative Acidity of a Substituted Phenol
Worked Example 13.1 Predicting the Relative Acidity of a Substituted Phenol Solution A carbonyl group is electron-withdrawing (in Section 9.8) p-Hydroxybenzaldehyde (pKa 7.89)is more acidic than phenol (pKa 9.89) OH p-Hydroxybenzaldehyde (pKa=7.89)
Solution ▪ A carbonyl group is electron-withdrawing (in Section 9.8) ▪ p-Hydroxybenzaldehyde (pKa = 7.89) is more acidic than phenol (pKa = 9.89) Worked Example 13.1 Predicting the Relative Acidity of a Substituted Phenol
13-3 Preparing Alcohols from Carbonyl Compounds Alcohols can be prepared from many other kinds of compounds including R R C= 0 C R OH R Alkene Carboxylic Ketone 0 acid C OR H Ester Aldehyde ROH RX ROR' Alcohols Alkyl halide Ether
Alcohols can be prepared from many other kinds of compounds including 13-3 Preparing Alcohols from Carbonyl Compounds
Preparing Alcohols from Carbonyl Compounds Alcohol synthesis Alcohols can be prepared by hydration of alkenes Direct hydration of alkenes with aqueous acid is generally a poor reaction in the laboratory Two indirect methods are commonly used =Hydroboration/oxidation yields the product of syn,non- Markovnikov hydration Oxymercuration/reduction yields the product of Markovnikov hydration H02 THF -OH trans-2-Methylcyclohexano (84%) CHa 1-Methylcyclohexene 40 1-Methylcyclohexanol (90%)
Alcohol synthesis ▪ Alcohols can be prepared by hydration of alkenes ▪ Direct hydration of alkenes with aqueous acid is generally a poor reaction in the laboratory ▪ Two indirect methods are commonly used ▪ Hydroboration/oxidation yields the product of syn, nonMarkovnikov hydration ▪ Oxymercuration/reduction yields the product of Markovnikov hydration Preparing Alcohols from Carbonyl Compounds
Preparing Alcohols from Carbonyl Compounds 1,2-Diol preparation Direct hydroxylation of an alkene with OsO followed by reduction with NaHSOg The OsO4 reaction occurs with syn stereochemistry to give a cis diol Acid-catalyzed hydrolysis of an epoxide Epoxide opening occurs with anti stereochemistry to give a trans diol CH3 CH3 0s04 NaHSO3 Pyridine H20 An osmate A cis 1,2-diol CH3 OH CH3 1-Methylcyclohexene RCO3H H30+ CH2Cl2 OH 1-Methyl-1,2-epoxy- A trans 1,2-diol cyclohexane
▪ 1,2-Diol preparation ▪ Direct hydroxylation of an alkene with OsO4 followed by reduction with NaHSO3 ▪ The OsO4 reaction occurs with syn stereochemistry to give a cis diol ▪ Acid-catalyzed hydrolysis of an epoxide ▪ Epoxide opening occurs with anti stereochemistry to give a trans diol Preparing Alcohols from Carbonyl Compounds