0.2 Grignard reaction  (Page 2/5)

This $\delta -$ carbon consequently has significant nucleophilic character. The Grignard reagent reacts well as a nucleophile with the $\delta +$ -carbon of the carbonyl group as a target. The C=O π-bond is broken and the carbonyl becomes an alcohol. In the process, a new carbon-carbon bond is formed between the Grignard reagent and the carbonyl carbon - now the alcohol carbon.

The intermediate alkoxymagnesium salt is neutralized by acid in the work-up to produce the alcohol product. Before we go on to look at more Grignard reactions with carbonyl groups, here is a problem for you to try.

• Identify the product (A-E) (5 points)

Answer:

Addition of GR to carbonyls:

GR adds to a carbonyl compounds to generate alcohols. A more modern interpretation extends the scope of the reaction to include the addition of Grignard reagents to a wide variety of electrophilic substrates:

Depending upon the amount of GR used and the substrate, it can give different types of products after working up the reaction. Here is an example:

Addition of GR to α, β unsaturated carbonyls:

GR adds to carbonyl center mainly in two fashions. Alkyl lithium halides add only in 1, 2-fashion because R-Li is a more reactive organometallic compound than others, so it prefers to add to most HARD carbonyl carbon center (since it is more electrophilic in nature). On the other hand, $R_2\text{CuLi}$ or $R-\text{MgX}/{\text{Cu}}^{2+}$ adds only in 1,4- fashion, because C-4 is soft towards electrophilicity and soft cuprate reagents prefer to add only to soft centers according to HSAB (Hard Soft Acid Base ) theory. Traditional GR (alkyl magnesium halide) is intermediate in its’ reactivity, so a mixture of 1, 2- and 1, 4- addition product is obtained. Here is an example of a GR adding to a α, β unsaturated carbonyl compound:

Most alcohols can be produced by a Grignard reaction. In deciding how to do this carry out the reaction, think about the Grignard reaction in reverse: if your target alcohol had been the result of a Grignard reaction, what would the carbonyl compound have to be? What would the Grignard reagent have to be?

Consider the scheme below for the synthesis of 1-phenyl-1-butanol via a Grignard reaction. Two different ways to synthesize this compound are shown. Can you think of a third?

Important facts:

Grignard reagent (RMgX) is a very polar reagent and a very strong Lewis base and therefore will be easily protonated by water, which acts as a strong acid when in contact with a Grignard reagent. The reagent’s reaction with water produces a gelatinous metal hydroxide. Since it reacts rapidly with the acidic hydrogen atom, the reaction must be carried out under dry conditions since even a small amount of moisture can destroy the reagent. The reactivity of Grignard reagent depends on mainly two factors:

1. Types of metal center (Li>K>Mg etc)

2. Types of halides present (I>Br>Cl) and

3. Types of solvent used.

In presence of different functional groups, the order of reactivity of GR is as follows:

Our experiment:

In this experiment, the addition of a nucleophilic Grignard reagent (1-methylbutylmagnesium bromide), to the electrophilic carbonyl carbon of an aldehyde (propanal) is performed.