Chapter 10 Outline: Alcohols Review Nomenclature, Structure & Physical Properties on your own 1. Acidity of Alcohols 2. Reactions of Alcohols 3. Reactions of Thiols You should do all the problems in the textbook, but these are some suggested homework problems: 10.15, 10.16, 10.18, 10.20, 10.21, 10.26 10.31, 10.35, 10.35 10.40, 10.42, 10.43, 10.45, 10-51 10.54. Page 1 of 23
Roadmap for chapter 10: Page 2 of 23
1. Acidity of Alcohols Alcohols have pkas in the range of 16-18. Only methanol has an acidity less than water (pka 15.5 and will protonate water preferentially). In general, all alcohols will be less polar and less acidic than water. What happens when water is in solution with ethanol (pka = 15.9)? Reaction of an alcohol with strong base, like sodium hydride, or Group I metals (Li, Na, K): CH 3 OH + NaH CH 3 ONa + H 2 sodium methoxide 2 CH 3 OH + 2 Na 2 CH 3 ONa + H 2 Page 3 of 23
2. Reactions of Alcohols how to make a good leaving group? All of these reactions you will learn in this chapters have one common theme converting the OH group into a good, stable leaving group!! What if we protonate the OH group? Does that become a better leaving group? A strong, non-halide containing acid like H 3 PO 4 or H 2 SO 4 or TsOH is used to protonate an alcohol. SO 3 H = TsOH p toluene sulfonic acid Page 4 of 23
a. ROH reaction with HCl, HBr & HI (converting a ROH RX) 1 o ROH react through an SN2 mechanism: 2 o /3 o ROH react through an SN1 mechanism: Page 5 of 23
b. Reaction with PX 3, X = Cl, Br (converting a ROH RBr) Reaction Observations: o This reaction can only be used with 1 o and 2 o ROH only o Reaction always occurs with inversion of configuration. o What substitution mechanism does this support? Mechanism? Page 6 of 23
c. Reaction with Thionyl Halide (SOX 2, X = Cl, Br) (converting a ROH RX) Reaction Observations: o This reaction can only be used with 1 o and 2 o ROH only o Reaction always occurs with inversion of configuration. o What substitution mechanism does this support? Mechanism? Page 7 of 23
d. Formation of Tosylates to provide good leaving groups What is important about this? Sulfonate anions are weak bases, making them VERY GOOD leaving groups. Look at H 2 SO 4 and consider its acidity: Since alcohols make poor leaving groups, reacting them with sulfonyl chlorides converts them into better leaving groups. Most common sulfonyl chloride reagents: O O H 3 C S Cl H 3 C S Cl O TsCl (Para-toluene sulfonyl chloride) O MsCl (mesyl chloride) Page 8 of 23
How do these reactions work overall? It s a two step reaction, (1) react the desired alcohol with the tosyl chloride without inversion, and (2) react it with the nucleophile leading to inversion of configuration: Page 9 of 23
e. Acid-catalyzed Dehydration of Alcohols to Alkenes (β-elimination reaction) Compare to: E1 mechanism is observed for 2 o and 3 o ROHs: How do you think the mechanism differs for a 1 o ROH? Page 10 of 23
Provide the mechanism for the following transformation: Page 11 of 23
f. Dehydration of ROH using POCl 3 & Pyridine (converting a ROH alkene) Mechanism? This mechanism is known to go through an E2 mechanism. Page 12 of 23
g. Pinnacol Rearragenment Page 13 of 23
h. Oxidation of Alcohols (no mechanism to know) Primary alcohols are oxidized to either aldehydes or carboxylic acids, depending on the reagent employed: Secondary alcohols are oxidized to ketones. Tertiary alcohols cannot be oxidized why? Common oxidizing reagents are: Page 14 of 23
1 o ROH give different products depending on the reagent used: OH PCC OH K 2 Cr 2 O 7 H 2 SO 4,H 2 O 2 o ROH give same products regardless of the reagent used: Provide the organic product for the following reactions. You do not need to balance the byproducts of the reaction. Page 15 of 23
i. Reaction of glycols with periodic acid Page 16 of 23
3. Reactions of Thiols L-Cysteine = Page 17 of 23
Alcohol Reactions. Provide correct organic product(s) and the mechanism for the following reactions. If stereochemistry pertains, ensure it is clearly demonstrated. If there is more than one product, then circle the major product. OH H 3 PO 4,heat Mechanism? OH POCl 3 pyridine Mechanism? Page 18 of 23
OH PBr 3 Mechanism? OH HBr Mechanism? Page 19 of 23
OH SOCl 2 pyridine Mechanism? OH 1. TsCl, pyridine O 2. ONa Mechanism? OH 1. NaH 2. CH 3 CH 2 Br Mechanism? Page 20 of 23
Provide viable steps to bring about the following transformation. Page 21 of 23
Provide viable steps to bring about the following transformation. Page 22 of 23
Provide viable steps to bring about the following transformation. Page 23 of 23