Organic 1b Topic 5

Other Carbonyl Functionalities

α,β-unsaturated carbonyl compound:

The C=C bond is electrophilic
The C=O bond is electrophilic

α,β-unsaturated carbonyl compounds are …

ambident electrophiles

What is an ambident electrophile?

A species which is electrophilic at more than one point and can react through different sites depending on the reaction conditions

What are the conditions for two double bonds in a diene to be conjugated?

1. double bonds must be separated from each other by a single bond

2. the π-MOs in each double bond must be able to overlap

Conjugated dienes tend to generate new … which can be viewed as new …

MOs, frontier orbitals

What are the two manners in which a nucleophile can add to an α,β-unsaturated carbonyl compound?

1,2 addition and 1,4 addition

The β-carbon of the alkene acts as a …

soft electrophile

The carbonyl carbon acts as a …

hard electrophile

1,2 addition results in addition to the …

carbonyl carbon

1,2 addition can be effected by a …

hard nucleoohile

Why do hard nucleophiles attack the carbonyl carbon preferentially?

Hard nucleophiles are smaller and more able to attack the congested/sterically hindered carbonyl group.

1,4 addition results in addition to the …

β-carbon of the alkene

1,4 addition can be effected by a …

soft nucleophile

Why do soft nucleophiles attack the β-carbon of the alkene preferentially?

Soft nucleophiles are larger and less charged, so it is easier for them to attack the less sterically hindered carbon. The MO of the alkene functional group is more diffuse on this carbon.

Examples of hard nucleophiles include:

hydroxide ion
fluoride ion
cyanide ion
Grignard reagents

Examples of soft nucleophiles include:

sulfur-based nucleophiles (RS^-, RSH)
secondary amines
benzene
alkene

1,2 addition mechanism:

Nucleophile attacks at carbonyl carbon. Negative charge accommodated on carbonyl oxygen. Acidic work-up neutralises negative charge to produce alcohol functionality.

1,4 addition mechanism:

Nucleophile attacks at the alkene carbon. Movement of electrons through π system. Negative charge accommodated on carbonyl oxygen. Addition of a proton across the new double bond, carbonyl double bond regenerated.

Hard nucleophiles and electrophiles are …

small, highly polarised species

Soft nucleophiles and electrophiles are …

larger, more diffuse species

The cyanide anion can react with … to form …

aldehydes and ketones, cyanohydrins

The cyanohydrin is formed via the rapid and reversible … reaction and is the … product

1,2 addition, kinetic

Conjugate addition of the cyanide anion is … because the nucleophile attacks at the β-carbon

slower

1,4 addition of the cyanide anion affords the … product, which is more stable due to the retention of the … bond

thermodynamic, C=O

Performing the reaction with the cyanide anion under kinetic conditions promotes … and achieves … addition

irreversibility, 1,2P

Performing the reaction with the cyanide anion under thermodynamic conditions achieves … addition

1,4

Organolithium reagents and Grignard reagents are … nucleophiles

hardO

Organocuprate and zinc reagents are … nucleophiles

soft

Organocuprates are synthesised …

in situ

Organocuprates are formed by reacting the appropriate organolithium or Grignard reagent with …

Cu(I)Br

Acetals are readily … under … to the corresponding alcohol and aldehyde or ketone

hydrolysed, acidic conditions

The presence of an aldehyde or ketone can present a … as they are reactive …

chemoselectivity problem, electrophiles

Acetals can be used as a …

protecting group

Imines are formed by the … of a … with an …

condensation, primary amine, aldehyde or ketone

The reaction to form an imine requires the addition of a … catalyst

mild acid

… conditions are needed to produce an imine

dehydrating

Imines are … electrophilic than aldehydes or ketones

less

Imines react similarly to carbonyls, with … conditions

more forcing

Imines can be protonated to generate … ions which are more …

iminium, electrophilic

Why is the nucleophilic substitution of alkyl halides with amines problematic?

It can often result in overalkylation as the amine afforded by the first substitution is more nucleophilic than the starting material.

Imines can be used to produce amines in a process called …

reductive amination

The reducing agent used to reduce imines is called …

sodium triacetoxyborohydride (Na(OAc)₃BH)

The reaction of an … with an … to form an amide is very slow

ester, amine

In order to produce an amide, an … must be generated in situ from the acid before the amine is added

activated ester

To convert a carboxylic acid to an acid chloride, add …

thionyl chloride (SOCl₂)

To convert a carboxylic acid to a thioester, add …

coenzyme A