CHEM 231 Lab
CHEM 231 Lab
Laboratory Case Study
A three-ring laboratory Specific new practical goals: to carry out the electrophilic epoxidation of a nonactivated olefin under microwave conditions to characterize a reaction mixture by TLC
Epoxides are important synthetic intermediates for medicinal chemists. For example, Efange and coworkers (J. Med. Chem. 1991, 34, 2638) have used epoxides to access -aminoalcohols (2) that exhibit interesting behavior as acetylcholine transport inhibitors (Scheme 1). O
Ph
NH
R
Ph
OH R
1
Safety Information
2
Scheme 1. Nucleophilic ring-opening of epoxides. One of the epoxides (4) used in this study was derived from estragole (4-allylanisole, 3), an essential oil found in a variety of herbs, including lemongrass, tarragon, fennel, and basil. The epoxidation was carried out in methylene chloride using m-chloroperbenzoic acid (mCPBA), a source of electrophilic oxygen (Scheme 2). mCPBA
O
CH2 Cl2
MeO
3
4
Scheme 2. Epoxidation of estragole. From a mechanistic standpoint, the oxygen is delivered from the mCPBA to the alkene in a concerted fashion (Scheme 3). Thermodynamically, the reaction is driven by the very weak O-O single bond in mCPBA. Even though a highly strained three-membered ring is created, a relatively weak C-C bond and the weak O-O bond are exchanged for two stronger C-O single bonds, which ends up being an enthalpically favorable transaction. m-chloroperbenzoic acid
O
Cl O
R
O
After the reaction is complete, the reaction mixture is subjected to aqueous extraction, washing with sodium metabisulfite (a mild reducing agent to destroy any excess mCPBA) and sodium bicarbonate (to remove the m-chlorobenzoic acid by-product). After removal of solvent and yield determination, the product is characterized by TLC and infrared (IR) analysis.
N
EtOH
MeO
not 100% pure) using the microwave reactor. The maximum reaction temperature should be 90°C to avoid thermal decomposition of mCPBA.
m-chlorobenzoic acid
O
Cl H
H O O
R
R
R
Scheme 3. Epoxidation mechanism. The reaction is reported to take 16 h at 20°C. Please carry out a 1-mmol scale reaction at a concentration of 0.20 M with 1.7 eq of mCPBA (note: reagent is
Estragole (4-allylanisole). Combustible liquid; harmful by ingestion; irritant. May be harmful if inhaled. Causes respiratory tract irritation. May be harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. m-Chloroperbenzoic acid. Organic peroxide; skin sensitizer; irritant. Heating may cause a fire. Causes skin irritation. May cause an allergic skin reaction. Causes serious eye irritation. May cause respiratory irritation. Dichloromethane. Harmful if swallowed. Causes skin and eye irritation. Suspected of causing cancer. May be harmful if inhaled. Causes respiratory tract irritation. Harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. Harmful if swallowed.
Laboratory Case Study
A three-ring laboratory Specific new practical goals: to carry out the electrophilic epoxidation of a nonactivated olefin under microwave conditions to characterize a reaction mixture by TLC
Epoxides are important synthetic intermediates for medicinal chemists. For example, Efange and coworkers (J. Med. Chem. 1991, 34, 2638) have used epoxides to access -aminoalcohols (2) that exhibit interesting behavior as acetylcholine transport inhibitors (Scheme 1). O
Ph
NH
R
Ph
OH R
1
Safety Information
2
Scheme 1. Nucleophilic ring-opening of epoxides. One of the epoxides (4) used in this study was derived from estragole (4-allylanisole, 3), an essential oil found in a variety of herbs, including lemongrass, tarragon, fennel, and basil. The epoxidation was carried out in methylene chloride using m-chloroperbenzoic acid (mCPBA), a source of electrophilic oxygen (Scheme 2). mCPBA
O
CH2 Cl2
MeO
3
4
Scheme 2. Epoxidation of estragole. From a mechanistic standpoint, the oxygen is delivered from the mCPBA to the alkene in a concerted fashion (Scheme 3). Thermodynamically, the reaction is driven by the very weak O-O single bond in mCPBA. Even though a highly strained three-membered ring is created, a relatively weak C-C bond and the weak O-O bond are exchanged for two stronger C-O single bonds, which ends up being an enthalpically favorable transaction. m-chloroperbenzoic acid
O
Cl O
R
O
After the reaction is complete, the reaction mixture is subjected to aqueous extraction, washing with sodium metabisulfite (a mild reducing agent to destroy any excess mCPBA) and sodium bicarbonate (to remove the m-chlorobenzoic acid by-product). After removal of solvent and yield determination, the product is characterized by TLC and infrared (IR) analysis.
N
EtOH
MeO
not 100% pure) using the microwave reactor. The maximum reaction temperature should be 90°C to avoid thermal decomposition of mCPBA.
m-chlorobenzoic acid
O
Cl H
H O O
R
R
R
Scheme 3. Epoxidation mechanism. The reaction is reported to take 16 h at 20°C. Please carry out a 1-mmol scale reaction at a concentration of 0.20 M with 1.7 eq of mCPBA (note: reagent is
Estragole (4-allylanisole). Combustible liquid; harmful by ingestion; irritant. May be harmful if inhaled. Causes respiratory tract irritation. May be harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. m-Chloroperbenzoic acid. Organic peroxide; skin sensitizer; irritant. Heating may cause a fire. Causes skin irritation. May cause an allergic skin reaction. Causes serious eye irritation. May cause respiratory irritation. Dichloromethane. Harmful if swallowed. Causes skin and eye irritation. Suspected of causing cancer. May be harmful if inhaled. Causes respiratory tract irritation. Harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. Harmful if swallowed.
