How to make Weinreb amides?

Weinreb amides could be synthesized through a mild Pd-catalyzed cross-coupling of 3-thienyl-, or 3-benzo[b]thienylboronic acid with N-methoxy-N-methylcarbamoyl chloride (Eqns 53 and 54) (2010JOC1251).

What is Weinreb amide used for?

The main synthetic use of Weinreb amides derives from their reactivity toward nucleophiles. They can be useful for the addition of Grignard or alkyllithium reagents to produce ketones. Other advantages are seen in the selective reduction of the Weinreb amides to the corresponding aldehydes.

Do Grignard reagents react with amides?

The acidity of carboxylic acids and 1º & 2º-amides acts to convert Grignard and alkyl lithium reagents to hydrocarbons (see equations), so these functional groups should be avoided when these reagents are used. ether soln. Imines themselves do not react with Grignard reagents.

How do you convert ester to ketone?

An ester (or an acid halide or an anhydride) reacts first with a Grignard reagent to form a ketone, which reacts further to give an alcohol.

Can amide be reduced by h2?

Catalytic hydrogenation can be used to reduce amides to amines; however, the process often requires high hydrogenation pressures and reaction temperatures to be effective (i.e. often requiring pressures above 197 atm and temperatures exceeding 200 °C).

What type of reaction is reductive amination?

Reductive amination (also known as reductive alkylation) is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde….

What can Grignard reagents react with?

Grignard reagents are formed by the reaction of magnesium metal with alkyl or alkenyl halides. They’re extremely good nucleophiles, reacting with electrophiles such as carbonyl compounds (aldehydes, ketones, esters, carbon dioxide, etc) and epoxides.

What is Grignard reagent give an example?

One such example is the Grignard reagent, represented as R—Mg—X, which can be prepared from haloalkanes as well as from aryl halides. The oxygen atom of diethyl ether (or THF) forms a complex with the magnesium atom of the Grignard reagent. These reagents in ether solution are very usefUl in organic synthesis.

What is ester formula?

Carboxylic acid esters, formula RCOOR′ (R and R′ are any organic combining groups), are commonly prepared by reaction of carboxylic acids and alcohols in the presence of hydrochloric acid or sulfuric acid, a process called esterification.

Can esters be reduced?

Esters can undergo hydride reduction with LiAlH4 to form two alcohols. The alcohol derived from the acyl group of the ester will be 1o and is typically considered the main product of the reaction. Sodium borohydride (NaBH4) is not a reactive enough hydride agent to reduce esters or carboxylic acids.

How can we reduce amide?

1. Amides, RCONR’2, can be reduced to the amine, RCH2NR’2 by conversion of the C=O to -CH2-
2. Amides can be reduced by LiAlH4 but NOT the less reactive NaBH4
3. Typical reagents : LiAlH4 / ether solvent, followed by aqueous work-up.

What is the difference between Amine and amide?

Amines and amides are two types of compounds found in the field of organic chemistry. The main difference between amine and amide is the presence of a carbonyl group in their structure; amines have no carbonyl groups attached to the nitrogen atom whereas amides have a carbonyl group attached to a nitrogen atom.

What happens after derivatisation of Weinreb amide?

However, after derivatisation to the corresponding Weinreb Amide, reaction with organometallics does give the desired ketones, as the initial adduct is stabilized and doesn’t undergo further reaction.

What was the reaction mechanism proposed by Weinreb and Nahm?

Weinreb and Nahm originally proposed the following reaction mechanism to explain the selectivity shown in reactions of the Weinreb–Nahm amide. Their suggestion was that the tetrahedral intermediate (A below) formed as a result of nucleophilic addition by the organometallic reagent is stabilized by chelation from the methoxy group as shown.

Can a Weinreb amide be used as a nucleophile?

This occurs even if the equivalents of nucleophile are closely controlled. The Weinreb–Nahm amide has since been adopted into regular use by organic chemists as a dependable method for the synthesis of ketones.

What are the steps in the reaction of amines?

• Mechanism: Required (addition-elimination-deprotonation) • Amine must have at least one hydrogen to begin. But 1º, 2º, or NH3all react well. • But 3º amines can’t work. • Some base is required for the deprotonation step and to absorb the HCl. For cheap amines, excess amine can simply be used.