Dehydrohalogenation of 2º Or 3º Alkyl Halides

ALKENES

Preparation:

1. Dehydrohalogenation
   of 2º or 3º alkyl halides:
   
2. Dehydration of alcohols:
   

Reactions:

1. Catalytic Hydrogenation:
   (Reduction)
   
2. Halogenation:
   (qualitative test)
   
3. Halohydrin formation:
   
4. Hydration (possible C+ rearrangement)
   or Hydration by
   Oxymercuration/Demercuration:
   (without C+ rearrangement)
   
5. Hydration by
   Hydroboration/Oxidation:
   (AntiMarkovnikov product):
   
6. Addition of H2SO4
   (qualitative test):
   
7. Addition of Alkyl Halides:
   (Markovnikov product)
   
8. Addition of HBr:
   (anitMarkovnikov product)
9. Oxidation without Cleavage
   (Hydroxylation)
   (Baeyer’s Test):
   
10. Oxidation with Cleavage
    

ALKYNES

Preparation:

1. Alkene halogenation/dehydrohalogenation:
   
2. Alkylation of alkynides:
   

Reactions:

1. Catalytic
   Hydrogenation:
   
2. Halogenation:
   (qualitative test)
   
3. Hydrohalogenation:
   
4. Hydration:
   

AROMATIC REACTIONS

Electrophilic Aromatic Substitution (EAS):

An electrophile (E+) substitutes for (replaces)
hydrogen on an aromatic ring:

1. Bromination:
   
2. Chlorination:
   
3. Iodination:
   
4. Nitration:
   
5. Sulfonation:
   
6. Friedel-Crafts Alkylation:
   

 The aromatic ring must be as reactive as a halobenzene. Less reactive rings do not react. Even amino-substituted aromatics don't react because the amino groups are converted to electron withdrawing groups (cationic quaternary amines) by reaction with the catalyst.

 Vinyl and aryl halides do not react.

 The alkyl halide can be methyl, ethyl, 2, or 3. Other primary alkyl halide C+'s rearrange.

 Polysubstitution produces mixed products. (The product is more reactive than the reagent.)

1. Friedel-Crafts Acylation:
   

 As with F.C. Alkylation, the aromatic ring must be as reactive as a halobenzene (amino groups also fail)

 Aryl halides will react. (Vinyl acyl compounds do not exist).

 Rearrangements do not occur.

 Polysubstitution will not occur. (The reagent is more reactive than the product.)

1. Reduction of Nitro Groups
   forming Aromatic Amines:
   
2. Alkali Fusion of Aromatic Sulfonates
   forming Phenols:
   

Nucleophilic Aromatic Substitution (NAS):
Aromatic compounds with a halogen ortho- or para- to one or more nitro-groups are weak electrophiles. Nucleophiles such as OH-, OR- and NH3 will substitute for (replace) the halogen.

1. Nitrophenols by NAS:
   
2. Nitroamines by NAS:
   
3. Oxidation of Alkylbenzene
   Side Chains:
   Benzylic C's with one or more H's are oxidized to carboxylic acids
   
4. Bromination of Alkylbenzene
   Side Chains:
   NBS (N-bromosuccinimide), in the presence of a peroxide, releases bromine free radicals (Br) which brominate the benzylic carbon rather than the ring.
5. Catalytic Reduction of Aromatics and Aryl Alkyl Ketones (from F.C. Acylations):
   

ALCOHOLS

Preparation:

1. Hydrolysis of Methyl or
   of 1º alkyl halides:
   (2 or 3  alkenes by E2)
   
2. Hydration (possible C+ rearrangement)
   or Hydration by
   Oxymercuration/Demercuration:
   (without C+ rearrangement)
   Hydration by
   Hydroboration/Oxidation:
   (AntiMarkovnikov product):
   
3. Hydride Reduction of
   Aldehydes,
   Ketones,
   Esters &
   Carboxylic Acids:
   
4. Grignard Reduction of
   Aldehydes,
   Ketones &
   Esters:
   (Grignard may be alkyl,
   aryl or vinylic but cannot
   be prepared when acidic
   groups are present
   with the halide)
   

ALCOHOL REACTIONS

1. Dehydration to Alkenes:
   
2. Conversion to Alkyl Halide:
   
3. Neutralizing a Strong Base:
   (Alcohols have pKb ca. 16 like H2O)
   
4. Oxidation of Alcohols:
   
5. Reduction to Alkanes:
   a) Dehydrate to alkenes (1. above), then hydrogenate (H2 / Ni) to alkane
   or
   b) Prepare alkyl tosyate (good leaving group), then replace with H:- (following)
   

THIOLS

Preparation:

(from hydrogen sulfide, H2S
and then hydrosulfide, HS- )

Reactions:

1. Reaction as acid
   with a base:
   
2. Sulfide formation by
   substitution (SN2) with
   Me, 1, or 2 alkyl halides:
   

ETHERS s

Williamson Ether Synthesis:
[alkoxide substitution (SN2)
with Me or 1 alkyl halide]
Epoxide Ring Opening:
(Most ethers are unreactive but
epoxides are reactive because
of their high ring strain.)

ALDEHYDES & KETONES

Preparation of Aldehydes:

1. Mild Oxidation of 1 Alcohols:
   
2. Reduction of Carboxylic Acid
   Derivatives:
   (use 1 equivalent of a mild hydride, i.e.,
   DIBAH in cold inert solvent @ -78C)

Preparation of Ketones:

1. Oxidation of 2 Alcohols:
   (mild or moderate oxidants)
   
2. Oxidative Cleavage of
   substituted alkenes:
   
3. Friedel Crafts Acylation
   of Aromatics:
   

 As with F.C. Alkylation, the aromatic ring must be as reactive as a halobenzene (and fails with animo groups)

 Aryl halides will react. (Vinyl acyl compounds do not exist).

 Rearrangements do not occur.

 Polysubstitution will not occur. (The reagent is more reactive than the product.)

1. Hydration of Alkynes:
   (non symmetrical internal
   alkynes give mixed products)
   
2. Acid chloride + Gilman Reagent:
   (a mild Grignard-like reagent, R’2CuLi
   in cold inert solvent @ -78C)
   

Reactions of Aldehydes and Ketones:

1. Oxidation of
   Aldehydes
   & Ketones:
   (aldehydes are easily oxidized)
   (ketones are not easily oxidized
   except under severe conditions.
   The enol isomer is cleaved.)
   

1. Hydration of
   Aldehydes
   & Ketones:
   [acid(H3O+) or base (OH-) catalysis
   is required as H2O is a weak Nu:-]
   (equilibrium favors the carbonyl)
   
2. Addition of HCN
   forming a cyanohydrin:
   (the cyanohydrin can be
   reduced to an amine or
   hydrolyzed to an acid)
   
3. Addition of Alcohols
   forming Acetals (diethers):
   (useful as protecting groups
   which are inert to strong bases)
   [Reaction is reversible. Use
   anhydrous acid to form acetal
   and aqueous acid back to the
   original aldehyde or ketone]
   
4. Grignard Reduction of
   Aldehydes to 2 Alcohols
   &
   Ketones to 3 Alcohols:
   
5. Hydride Reduction of
   Aldehydes to 1 Alcohols
   &
   Ketones to 2 Alcohols:
   
6. Reduction of Carbonyl (C=O)
   group to Methylene (CH2) group
   by Wolf Kishner (N2H4 + KOH)
   or Clemmensen (Zn[Hg] + H3O+)
   
7. Addition of 1 Amines
   forming Imines
   or
   2 Amines
   forming Enamines:
   

Examples of Imines:
(Derivatives)

1. Conjugate 1,4-Addition
   of 1 equiv. of Amine
   or
   1 equiv. of Gilman Reagent:
   (In , -unsaturated carbonyls,
   addition occurs at the -carbon
   and the -carbon is saturated
   while the carbonyl is unreacted)
   [It only works with these 2 reagents.
   Other nucleophiles add directly to
   the carbonyl C]
   (Excess amine or Gilman reagent
   will add to the carbonyl carbon
   after the  and -carbons are
   saturated)
   

CARBOXYLIC ACIDS

Preparation:

1. Oxidation of Alkylbenzene
   Side Chains:
   (Benzylic C's with one or more H's
   are oxidized to carboxylic acids)
   

1. Oxidation with Cleavage:
   
2. Oxidation of 1 Alcohols:
   (with moderate oxidants)
   
3. Oxidation of Aldehydes:
   (mild or moderate oxidants)
   
4. Hydrolysis of Nitriles:
   (acidic or basic hydrolysis)
   
5. Grignards are
   Carboxylated:
   

Reactions:

1. Reduction with
   LiAlH4 or BH3
   in THF solvent:
   
2. Neutralization with
   a base:
   

1. Conversion to
   Acid Chloride:
   
2. Dehydration to
   Acid Anhydride:
   (Reaction is reversible.
   Anhydride can be
   hydrated back to
   2 carboxylic acids)

ORANOMETALLICS

Preparation:

1. Organosodium or
   Organolithium:
   (Finely dispersed metal is
   added to dilute RX in HC solvent)
2. Wurtz Coupling:
   (When Na is not dispersed, Me
   or 1 RX react with R-Na via SN2)
3. Grignard Reagents:
   (Finely divided Mg in ether
   is inserted between any R-X bond)
4. Gilman Reagent:
   (Any alkyllithium complexes
   with CuI in ether)

Reactions:

1. Organosodium/lithium
   converted to alkanes:
   (And other reactions
   where R is nucleophilic)
2. Grignards converted
   to alkanes:
   (And other reactions
   where R is nucleophilic)
3. Substitution with any
   RX forming larger alkanes:
   (And other reactions
   where R is nucleophilic)
   

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ORGANIC REACTIONS