Topic 13: Carbonyls: Conjunction and Acetals Flashcards
Two double bonds in a diene are conjugated when they are … and …
separated from one another by one (usually a single) bond
he pi-MOs in each double bond can overlap.
Conjugation affects both the … and the …properties of the …, and therefore the … of the molecule. Conjugated dienes can be viewed as a … as they share …
physical
chemical
functional group
single functional group
MOs
α,β-unsaturated carbonyl groups are …: a nucleophile can attack at …
ambident electrophiles
more than one site
In the first step, the nucleophile attacks at the …. Since the olefin is … with the …, electron density can be pushed on to the … .The … is called an enolate (very important nucleophiles). Different nucleophiles display different … when reacting with … .
‘hard’ nucleophiles react with … in a … whilst ‘soft’ nucleophiles react preferentially in a … . Hard nucleophiles and electrophiles are … species while soft nucleophiles and electrophiles are … species because MO of functional group is more … on …
β-carbon
conjugated
carbonyl group
electronegative oxygen atom of the carbonyl group
negatively charged intermediate
regioselectivity
α,β-unsaturated systems
α,β-unsaturated carbonyls
1,2-fashion
1,4-fashion
small, highly polarised
larger, more diffuse
diffuse
C-4
Examples of soft and hard nucelophiles
hard: -OH -F -CL
soft: -RS/RSH RNH2 alkene/aromatic compounds
The cyanide anion can react with … to form … . This … reaction is generally …; the cyanohydrin represents the … product (the one formed fastest).
… is slower since the nucleophile is attacking at the …, which is less …, than the … . This mode of addition, however, provides the … (the most stable); it is better to retain a strong … than a weaker … bond in the product.
So if we perform the reaction under kinetic conditions (promote irreversibility) then we achieve … . If we perform the reaction under thermodynamic conditions we achieve …
aldehydes and ketones
cyanohydrins
1,2-addition
rapid and reversible
kinetic
Conjugate addition
β-carbon
electron-deficient and electrophilic
carbonyl carbon
thermodynamic product
C=O bond
C=C
1,2-addition
1,4-addition
Organolithium reagents and Grignard (organomagnesium) reagents are termed … and react with … to provide the …
Organocopper and zinc reagents are termed … and react with … to provide the …
‘hard’ nucleophiles
α,β-unsaturated carbonyl compounds
1,2-addition product preferentially
‘soft’ nucleophiles
α,β-unsaturated carbonyl compounds
1,4-addition producT
Acetals functional group
sp3-hybridised carbon atom that is bonded to two oxygen atoms,
which are themselves attached to carbon atoms
Acetals are formed using the same mechanism as … and are usually done under … conditions. Acetal formation is a … process, therefore, to drive the reaction over to the product, it is necessary to use
an excess of … or provide a method for removing water e.g. … .Acetals are not prone to … under … or … conditions; however, in the presence of …,
they are … readily to the corresponding … and …
hydrates
acidic
equilibrium
alcohol
removing water
a dehydrating agent or remove the water
by azeotropic distillation (Dean-Stark)
hydrolysis
neutral
basic
acid
hydrolysed
alcohol
aldehyde/ketone
Identify the acetal carbon, i.e., … .Cleave the two … bonds. Convert the two … atoms into … and make the … atom into the carbon of a …
the sp3-hybridised carbon atom that is directly bonded to two oxygen atoms
acetal C–O
oxygen
alcohols
sp3-hybridised acetal carbon
carbonyl group
Aldehydes and ketones are … and sometimes their presence in a molecule can present … problem for reactions that need to be carried out on other functionality elsewhere in the molecule. If this is the case, the … is usually masked in some way using a …, such that it can no longer … .The … can then be removed at a later stage
reactive electrophiles
chemoselectivity
reactive carbonyl group
protecting group
behave as an electrophile
protecting group
Imines are the … and are vital functional groups. They are formed by the … with a … .
The reaction normally requires the addition of a … to … as amines … .We also apply … to drive the reaction to completion. As with acetals, the reaction can be … by …
nitrogen analogues of carbonyls
condensation of a primary amine
aldehyde or a ketone
acid catalyst
promote the reaction
are not brilliant nucleophiles
dehydrating conditions
driven back to the starting materials
addition of water
Imines are … than aldehydes and ketones (electronegativity of N vs O). So whilst imines do react similarly to carbonyls, we need … .For example, we can … which are much more … Imines
less electrophilic
more forcing conditions
protonate imines to generate iminium ions
electrophilic
The Problem with Synthesising Amines by Nucleophilic Substitution.
What should happen?
What happens in practice?
Solution …
Nucleophilic substitution of a 1° amine with an alkyl halide should provide the corresponding 2° amine and a 2° amine with an alkyl halide should provide the corresponding 3° amine
The more substituted amine product in these reactions is often more nucleophilic than the starting amine leading to over-alkylation
Reaction called a reductive amination. The reducing used here is called sodium triacetoxyborohydride [Na(OAc)3BH] and is used as it is too weak to
reduce the carbonyl starting material but can reduce the iminium ion – chemoselective reducing agent
Due to its unique ability to be both a … – this means it can readily form interactions with many biological targets such as proteins. However, forming amides is tough to complete. Reacting … to generate an amide has limitations. Forming an amide directly from a … isn’t possible. Instead, we have to generate a … from … . Common methods of this: …
H-bond donor and acceptor simultaneously
an amine with an ester
carboxylic
‘activated ester’ in situ
the acid and then add the amine
Thiomyl chloride, DCC, Coenzyme A
