Alcohol Synthesis With Reduction Reactions

What are the three reduction mechanisms that can be used to synthesis alcohols from carbonyls?

Catalytic hydrogenation, sodium borohydride, and lithium aluminum hydride

In CATALYTIC hydrogenation, what is REQUIRED for this mechanism to occur?

Both high TEMPERATURE and PRESSURE are required

In catalytic hydrogenation, what is the reagent used in this mechanism?

H₂/Pt, Pd, or Ni

What is changed in catalytic hydrogenation?

ALL pi bonds are reduced, and the carbonyl group is changed to a HYDROXY group

With sodium borohydride in the reduction mechanism, what does this reducing agent look like?

NaBH₄/ EtOH, MeOH, H₂O

What is the strength of the reducing agent in sodium borohydride reduction mechanism?

The reagent is MILDY strong

In sodium borohydride reduction mechanism, the carbonyl is reduced to WHAT different functional groups?

Aldehydes and ketones can form when the carbonyl is reduced

With lithium aluminum hydride, what is the strength of the reducing agent?

It is a STRONG reducing agent

What does the reagent look like for lithium aluminum hydride?

LiAlH₄ or LAH / H₂O or H₃O

In lithium aluminum hydride reduction mechaism, what is the carbonyl group reduced to?

Aldehyde, ketone, ester, and carboxylic acids

What TWO functional groups are reduced to PRIMARY alcohols in lithium aluminum hydride?

Ester AND carboxylic acid; ROH also produced in ester

To form a PRIMARY alcohol, what functional group and reaction mechanism would be needed?

Reacting an ALDEHYDE with either sodium borohydride or lithium aluminum hydride

To form a SECONDARY alcohol, what reaction mechanism and functional group would be needed?

A ketone undergoing the sodium borohydride or lithium aluminum hydride mechanism

When a KETONE undergoes sodium borohydride/ lithium aluminum hydride mechanism, what are the steps that occur?

1) Hydride acts as nucleophile and attacks the ketone, forming an alkoxide ion

2) Alkoxide ion becomes protonated, and forms alcohol

Review Ester and Lithium Aluminum Hydride Mechanism

How does the SYMMETRY of the ketone affect stereochemistry?

If the beginning ketone is NOT symmetrical, NEW chiral centers forms and ENANTIOMERS will be present

When the ketone is NOT symmetrical and stereochemistry WILL occur, which mechanism for alcohol synthesis from carbonyls is not included?

Catalytic hydrogenation

How can diols be synthesized with reduction reactions?

A molecule with TWO carbonyl groups can undergo any of the reduction mechanisms

Review mechanism of CYCLIC ester with lithium aluminum hydroxide

Diol synthesis can also occur via dihydroxylation. What are the TWO kinds of dihydroxylation that exist?

Anti and Syn

For diol synthesis of anti-dihydroxylation, what reagents are used?

1) MCPBA/ H₃O

2) RCO₃H/H₂O

For diol synthesis from SYN dihydroxylation, what reagents are used?

1) OsO₄/H₂O₂,NMO, NaHSO₃ + H₂O

2) KMnO₄ (cold, dilute)/ NaOH

What SUBSTITUTION mechanisms can cause alcohol synthesis?

SN1 and SN2

In a SN2 mechanism for ALCOHOL synthesis, what is the preferred reactivity of the alkyl halide and preferred nucleophile?

1) either PRIMARY or METHYL halide

2) STRONG nucleophile

After a SN2 mechanism has occurred, what is the reactivity of the alcohol that is formed?

A PRIMARY alcohol will form

With a SN1 reaction to synthesize alcohols, what is the reactivity of the alkyl halide that is preferred and the nucleophile?

1) TERTIARY alkyl halide

2) WEAK nucleophile

What is is about the SN1 mechanism that is unique?

E1 mechanism competes as well

SECONDARY alkyl halides are not mentioned in alcohol synthesis. Why?

Secondary alkyl halides will undergo E2 mechanism to make alkene

Alcohols can also be synthesized from alkenes with HYDRATION reactions. What do these hydration reactions involve?

Acid catalyzed hydration, oxymercuration-demercuration, and hydroboration-oxidati9on

In acid catalyzed hydration, what is the reagent used?

H₂SO₄ (diluted)

What is the regioselectivity, stereochemistry, and rearrangement for acid catalyzed hydration of an alkene to form an alcohol?

-Regioselectivity: Markovnikov

-Stereochemistry: Only if NEW chiral center is formed

-Rearrangements ARE possible

With oxymercuration-demercuration to form an alcohol from an alkene, what reagent is involved?

Hg(OAc)₂,H₂O/ NaBH₄

What is the regioselectivity, stereochemistry, and rearrangement of oxymercuration-demercuration hydration mechanism?

-Regioselectivity: markovnikov

-Stereochemistry: ANTI when applicable

-Rearrangements: NOT possible

With hydroboration-oxidation hydration to synthesize an alcohol from an alkene, what is the reagent used?

BH₃ + THF / H₂O₂ + NaOH

What is the regioselectivity, stereochemistry, and rearrangement for the hydration reaction of hydroboration-oxidation?

-Regioselectivity: ANTI-Markovnikov

-Stereochemistry: SYN when applicable

-Rearrangements: NOT possible

Substitution mechanisms can also be used to convert alcohols to alkyl halides. Which substitution mechanisms are these?

SN1 and SN2

Between BOTH SN1 and SN2 reactions, what is the WORST leaving group to use?

-OH

For the SN1 reaction, what degree of reactivity for the alcohol is preferred?

TERTIARY alcohol

In the SN1 reaction of converting an alcohol to alkyl halide, what degree of reactivity is the product?

TERTIARY alkyl halide

For the SN1 reaction of alcohol to alkyl halide, what is the stereochemistry and rearrangement?

-Stereochemistry: racemization; enantiomers are formed with a chiral center

-Rearrangements: CAN occur

For the SN2 reaction of converting alcohol to alkyl halide, what is the degree of reactivity for the alcohol that is preferred?

PRIMARY alcohol

In the SN2 reaction of alcohol to alkyl halide, what is the degree of reactivity of alkyl halide that is produced?

A PRIMARY alkyl halide is formed

What happens to the stereochemistry when SN2 reaction of alcohol to alkyl halide occurs?

Inversion

When converting an alcohol to alkyl halide via SN2, the size of the carbon chain influences the reagent. How?

If the carbon chain containing the alcohol has LESS then 6 carbons, the reagent will be HCL/ ZnCl₂

If SN2 is used to convert an alcohol to alkly halide, and the carbon chain containing the alcohol group is greater than 6 carbons, what reagents are used?

SOCL₂/ py OR PBR₃

SECONDARY alcohols can be used to convert alcohols to alkyl halides. What substitution mechanism is used?

SN2 is used

For the conversion of a SECONDARY alcohol to alkyl halide, what is the reagent used in a SN2 reaction?

TsCl, Py/ NaX

Review cyanide and ether formation of SN2 mechanism with secondary alcohol

Alcohols can be converted into alkenes. By what mechanisms is this possible?

E1 and E2 mechanism

For an E1 mechanism of alcohol to alkene, what degree of reactivity is preferred for the alcohol?

Tertiary OR secondary alcohol is preferred

For the E1 mechanism of alcohol to alkene, what reagent is used?

concentrated H₂SO₄ and heat

In the E1 mechanism of alcohol to alkene, what rule is followed and what happens with rearrangements?

Zaitsev rule, and rearrangements ARE possible

With the E2 mechanism of converting alcohol to an alkene, what degree of alcohol reactivity is preferred?

PRIMARY alcohol is preferred

In E2 mechanism of converting alcohol to alkene, what reagents are used in this mechanism?

concentrated H₂SO₄/heat, and POCl₃/py

In the E2 mechanism, what happens to the rule and rearrangement?

If there is a BULKY base, Hoffman rule is followed instead of Zaitsev. Rearrangements are NOT possible

In the case that an E2 mechanism contains a hydroxide ion attached to the chain, what reagent can be used to turn the hydroxide ion into a better leaving group?

TsCl