Chapter 9 Part 2 BN

cyanohydrin

compounds with a hydroxyl group and a cyano group attached to the same carbon

hemiacetal

contains both alcohol and ether functional groups on the same carbon atom

how do Grignard reagents act toward carbonyl compounds?

- Grignard reagents act as carbon nucleophiles toward carbonyl compounds - the R group of the Grignard reagent adds irreversibly to the carbonyl carbon, forming a new carbon-carbon bond - in terms of acid-base reactions, the addition is favorable because the product (an alkoxide) is a much weaker base than the starting carbanion (Grignard reagent) - the alkoxide can be protonated to give an alcohol

because alcohols are weak nucleophiles, what is required?

- a catalyst - the product is a hemiacetal; it contains both alcohol and ether functional groups on the same carbon atom - the addition is reversible

the reaction of a Grignard reagent with a carbonyl compound provides a useful route to

- alcohols - the type of carbonyl compound chosen determines the class of alcohol produced

what type of nucleophiles are alcohols?

- alcohols are oxygen nucleophiles - they add to the C=O bond, the OR group becoming attached to the carbon and the proton becoming attached to the oxygen

aldehydes that have an appropriately located hydroxyl group in the same molecule may exist in equilibrium with a

- cyclic hemiacetal, formed by intramoelcular nucleophilic addition - in a cyclic hemiacetal, the ether functional group is cyclic

compounds with a hydroxyl group that is four or five carbons away from the aldehyde group tend to form

- cyclic hemiacetals and acetals because the ring size (five or six-membered) is relatively strain free

protonation of hemiacetal

- either oxygen of the hemiacetal can be protonated - when the hydroxyl oxygen is protonated, loss of water leads to a resonance-stabilized carbocation - reaction of this carbocation with the alcohol, which is usually the solvent and is present in large excess, gives (after proton loss) the acetal - the mechanism is like an SN1 reaction - EACH STEP IS REVERSIBLE

to summarize: aldehydes and ketones react with alcohols to form

- first, hemiacetals and then, if excess alcohol is present, acetals

the type of carbonyl compound chosen to react with a Grignard reagent determines the class of alcohol produced:

- formaldehyde gives primary alcohols - other aldehydes give secondary alcohols - ketones give tertiary alcohols - note that only ONE of the R groups attached to the hydroxyl-bearing carbon of the alcohol comes from the Grignard reagent. The rest of the alcohol's carbon skeleton comes from the carbonyl compound.

acetal

- has two ether functional groups on the same carbon atom

ammonia, amines, and certain related compounds

- have an unshared electron pair on the nitrogen atom and act as nitrogen nucleophiles toward the carbonyl carbon atom - the tetrahedral addition product that is formed first is similar to a hemiacetal, but with an NH group in place of one of the oxygens - these addition products are normally not stable and eliminate water to form a product with a carbon-nitrogen double bond

hydrogen cyanide reacting with the carbonyl group of aldehydes and ketones

- hydrogen cyanide adds reversibly to the carbonyl group of aldehydes and ketones to form cyanohydrins, which are compounds with a hydroxyl and a cyan group - a basic catalyst is required such as KOH - hydrogen cyanide has no unshared electron pair on its carbon, so it cannot function as a carbon nucleophile - the base catalyst converts some of the hydrogen cyanide to cyanide ion (NC-) which then acts as a carbon nucleophile

with primary amines reacting with a C=O group, the products are called

- imines, which are compounds containing a carbon-nitrogen double bond - they are like carbonyl compounds except that the O is replaced by NR - they are important intermediates in some biochemical

the mechanism of hemiacetal formation

- involves 3 steps - first, the carbonyl oxygen is protonated by the acid catalyst - the alcohol oxygen then attacks the carbonyl carbon and a proton is lost from the resulting positive oxygen - each step is reversible - in terms of acid-base reactions, the starting acid catalyst in each step is converted to a product acid of similar strength

is acetal formation reversible or irreversible?

- it is a reversible process that involves a series of equilibria - they can be driven in the forward direction by using a large excess of alcohol or by removing water as it is formed - it can be driven in the backward direction (acetal being hydrolyzed to its aldehyde or ketone and alcohol components) by treatment with excess water in the presence of an acid catalyst - the hemiacetal intermediate in both the forward and reverse processes usually cannot be isolated when R' and R'' are simple alkyl or aryl groups

water, like alcohols, is an

- oxygen nucleophile and can add reversibly to aldehydes and ketones - for example, formaldehyde in an aqueous solution exists mainly as its hydrate - with most other aldehydes or ketones, however, the hydrates cannot be isolated because they readily lose water to reform the carbonyl compound, that is, the equilibrium constant is less than 1

in the presence of excess alcohol, hemiacetals

- react further to form acetals - the hydroxyl group of the hemiacetal is replaced by an alkyl group

^ this reaction is normally carried out by

- slowly adding an ether solution of the aldehyde or ketone to an ether solution of the Grignard reagent - after all of the carbonyl compound is added and the reaction is complete, the resulting magnesium alkoxide is hydrolyzed with aqueous acid

the acid-catalyzed cleavage of acetals compared to acid-catalyzed cleavage of simple ethers

- the acid-catalyzed cleavage of acetals occurs much more readily than the acid-catalyzed cleavage of simple ethers because the intermediate carbocation is resonance stabilized - however, acetals, like ordinary ethers, are stable toward bases

other organometallic reagents, such as organolithium compounds and acetylides, react with carbonyl compounds in a similar fashion to

Grignard reagents - ex: a ketone + sodium acetylide

can only aldehydes form acetals?

NO! ketones can also form acetals