CHEM 39, Spring 2007
Tentative list of reactions to be covered in Chem 39:
(m) = mechanism covered
SYNTHESIS OF CARBONYL COMPOUNDS
Aldehydes and Ketones
1. Oxidation of alcohols (m) (1° alcohols to aldehydes (PCC); 2° alcohols
to ketones (PCC, Jones, etc.)
2. Hydration of alkynes (m) (Hg++ catalyzed, via enols)
3. Ozonolysis of alkenes (reductive work up, Zn/AcOH)
4. Friedel-Crafts acylation (m)
5. Reaction of organo-copper reagents (R2CuLi) with acid halides
6. Controlled reduction of acid halides to aldehydes (LiAlH[OC(CH3)3](m))
7. Controlled reduction of esters to aldehydes (m) (DIBAH)
8. Controlled reduction of nitriles to aldehydes (m) (DIBAH)
Carboxylic acids
1. Oxidation of 1° and 2° alkylbenzenes (KMnO4)
2. Oxidative cleavage of alkenes with at least one vinylic hydrogen (KMnO4)
3. Oxidation of 1° alcohols (Jones (m) ) and aldehydes (Tollens, Jones)
4. Hydrolysis of nitriles
5. Carboxylation of Grignard reagents (m)
Acid halides
1. Reaction of carboxylic acids with SOCl2, or PBr3 (m)
Anhydrides
1. Reaction of carboxylate anions with acid halides (m)
2. Dehydration of acids
Esters
1. Reaction of acids with alcohols (Fischer esterification) (m)
2. Reaction of carboxylate anions with alkyl halides (SN2) (m)
3. Reaction of acid halides with alcohols in the presence of base (m)
Amides
1. Reaction of acids with amines (not practical, high temperatures required)
2. Reaction of anhydrides (acetic anhydride) with amines (m)
3. Reaction of esters with amines
4. Reaction of acid halides with amines (m) (base required to scavenge HCl)
Nitriles
1. Dehydration of 1° amides (m)
2. Reaction of alkyl halides with cyanide ion (SN2) (m)
3. Addition of HCN (base catalyzed) to aldehydes or ketones (m)
REACTIONS OF CARBONYL DERIVATIVES
Aldehydes and Ketones
1. Addition of HCN (m) (base catalyzed, reversible, ----> cyanohydrines)
2. Addition of H2O (m) (acid or base catalyzed, reversible, -----> hydrates)
3. Addition of ROH (m) (acid catalyzed, reversible, -----> acetals (ketals))
4. Addition of amines (m) (acid catalyzed, reversible, 1°amines ---->
imines, 2° amines ----> enamines)
5. Wolff-Kishner and Clemmensen reductions (ketones -----> alkane)
6. Addition of hydride (m) (irreversible: NaBH4, LiAlH4, ----> alcohols)
7. Addition of organometallics or carbanions (m) (irreversible: RMgX, RLi,
acetylides, ----> alcohols)
8. Addition of ylides (m) (irreversible, Ph3PCR2, ----> alkenes)
9. Conjugate addition to a,b-unsaturated aldehydes and ketones: (amines (m),
HCN (m), R2CuLi)
10. alpha-Halogenation of aldehydes and ketones (m) (X2/AcOH ----> a-halo
aldehydes or ketones; if followed by treatment with base ----> a,b-unsaturated
aldehydes or ketones)
11. Haloform reaction (m) (NaOH, X2 ----> carboxylic acid and haloform)
12. alpha-Alkylation (m) (LDA, alkyl halide ----> alpha-alkyl ketones)
13. Acetoacetic esters syntheses (m)
Carboxylic Acids
1. Reduction (LiAlH4, BH3-THF ----> 1° alcohols)
2. Decarboxylation (carboxylic acids with a carbonyl group in b position)
3. Conversion to acid halides (m) (SOCl2, PBr3, ----> acid halides)
4. Dehydration to anhydrides (practical only for cyclic anhydrides)
5. Reaction of carboxylates with 1° alkyl halides (m) (SN2, ----> esters)
6. Fischer esterification (m) (small molecular weight alcohols, acid catalyzed
----> esters)
7. Reaction with amines (mainly proton transfer, at very high temperature
---->amides)
8. Hell-Volhard-Zelinskii reaction (m) (Br2, PBr3, followed by H2O ---->
alpha-bromo acids)
Acid halides
1. Friedel-Crafts acylation of aromatic substrates (m) (----> aromatic
ketones)
2. Hydrolysis (m) (with H2O or hydroxide ----> carboxylic acids)
3. Alcoholysis (m) (with alcohols and base ----> esters)
4. Aminolysis (m) (with amines and base ----> amides)
5. Reaction with carboxylate anions (m) (----> anhydrides)
6. Reduction (with LiAlH4 (m) ----> alcohols; with LiAlH[OC(CH3)3] (m)
----> aldehydes)
7. Reaction with diorganocopper reagents (----> ketones)
8. Reaction with Grignard or organolithium reagents (m)(----> 3° alcohols)
Anhydrides
1. Hydrolysis (m) (water or hydroxide ----> acids)
2. Alcoholysis (m) (with alcohols ----> esters)
3. Aminolysis (m) (with amines ----> amides)
4. Reduction (m) (with LiAlH4 ----> primary alcohols)
Esters
1. Hydrolysis (acid (m) or base (saponification) (m) catalyzed ----> acids
and alcohols)
2. Aminolysis (with amines ----> amides)
3. Reduction (with LiAlH4 (m)----> 1° alcohols; with DIBAH (m)---->
aldehydes)
4. Reaction with Grignard or organolithium reagents (m) (----> 3° alcohols)
5. alpha-Alkylation (m) (use LDA, alkyl halide ----> alpha-alkyl esters)
6. Malonic ester syntheses (m)
Amides
1. Hydrolysis (m) (acid or base catalyzed, ----> carboxylic acids and amines)
2. Reduction (LiAlH4 ----> amines)
3. Dehydration (m) (1° amides ----> nitriles)
Nitriles
1. Hydrolysis (m) (acid or base catalyzed ----> amides ----> carboxylic
acids and ammonia)
2. Reduction (m) (LiAlH4 ----> 1° amines; DIBAH ----> aldehydes)
3. Reaction with Grignard or organolithium reagents (m) (----> ketones)
4. alpha-Alkylation (m) (LDA, alkyl halide ----> alpha-alkyl nitriles)
Condensation Reactions of Carbonyl Compounds
1. Aldol reaction (m) (base catalyzed, reversible condensation of aldehydes
or ketones , ---> beta-hydroxy carbonyl compounds, or alpha,beta-unsaturated
carbonyl compounds)
2. Claisen condensation (m) (base induced condensation of esters ---->
beta-keto esters)
3. Dieckmann cyclization (m) (intramolecular Claisen condensations)
4. Michael reaction (m) (conjugate addition of enolates of 1,3-dicarbonyl
compounds, ----> tricarbonyl compounds)
5. Stork enamine reaction (m) (conjugate addition of enamines ----> 1,5-dicarbonyl
compounds)
6. Robinson annulation (m) (Michael condensations followed by aldol reactions
----> cyclic carbonyl compounds)
SYNTHESIS AND REACTIONS OF AMINES
Synthesis of amines
1. Alkylation of ammonia and amines with alkyl halides (m)
2. Alkylation with azide (m)
3. Alkylation of imides (Gabriel synthesis) (m)
4. Reduction of nitriles or amides (m)
5. Reductive amination (m)
6. Hofmann and Curtius Rearrangements (m)
7. Reduction of aromatic nitro compounds
Reactions of amines
1.Alkylations and acylations (m)
2. Hofmann elimination (m)
3. Sandmeyer reaction of diazonium salts
REACTIONS OF SYNTHETIC POLYMERS
1. Radical chain polymerization of alkenes (m)
2. Anionic polymerization of alkenes with EWG (m)
3. Cationic polymerization of alkenes with EDG (m)
4. Ziegler-Natta polymerization (m-outline)
5. Preparation of polyamides, polycarbonates, polyurethanes, and polyureas
(m)
REACTIONS INVOLVING NATURAL PRODUCTS
1. Hemiacetal formation in sugars and mutarotation (m)
2. Formation of glycosides (acetals) (m)
3. Reduction of monosaccharides (m)
4. Oxidation of monosacharides
5. Kiliani-Fischer chain lengthening in sugars (m)
6. Wohl degradation (chain shortening in sugars) (m)
7. Synthesis of amino acids from carboxylic acids (m)
8. Strecker synthesis of amino acids (m)
9. Reductive amination of a-ketoacids (m)
10. Amidomalonate synthesis (m)
11. Edman degradation (peptide sequencing, outline)
12. Solid-phase peptide synthesis (oultline)
13. DNA sequencing (outline)
14. DNA (oligonucleotides) synthesis (outline)
PERICYCLIC REACTIONS (symmetry rules)
1. Electrocyclic reactions (m) (conjugated polyenes <====> cyclic poly(n-1)enes,)
2. Cycloaddition reactions (m) (Diels Alder reactions (4 + 2 additions) ----->
cyclic 6-membered enes)