Basicity Grignard reagents

Total basicity is measured by standard acid—base titration techniques. The activity divided by the total basicity should be greater than 90%. If it is not, then the Grignard reagent should be checked for unreacted alkyl or aryl haUde, homo-coupled product, hydrolysis products, and oxidation products. 

Sometimes the strongly basic properties of Grignard reagents can be turned to synthetic advantage. A chemist needed samples of butane specifically labeled with deuterium, the mass 2 isotope of hydrogen, as shown ... 

Nucleophiles other than Grignard reagents also open epoxide rings. These reactions are carried out in two different ways. The first (Section 16.12) involves anionic nucleophiles in neutral or basic solution. 

The carbon-nitrogen triple bond of nitriles is much less reactive toward nucleophilic addition than is the car bon-oxygen double bond of aldehydes and ketones. Strongly basic nucleophiles such as Grignard reagents, however, do react with nitriles in a reaction that is of synthetic value ... 

Some recent studies have underlined the effect that certain physical properties of the reaction medium have in governing the nature and yields of the products obtained when indole Grignard reagents react with alkyl or alkynyl halides. Such factors include the basicity and dielectric constant of the medium and its ability to solvate any of the reacting species. ... 

In an initial step, dibenzo[a,d] cyclohepten-5-one is reacted with the Grignard reagent of 3-di-methylaminopropyl chloride and hydrolyzed to give 5-(3-dimethylaminopropyl)-dibenzo[a,d] -[1,4] cycloheptatriene-5-ol. Then 13 g of that material, 40 ml of hydrochloric acid, and 135 ml of glacial acetic acid is refluxed for 314 hours. The solution is then evaporated to dryness in vacuo and added to ice water which is then rendered basic by addition of ammonium hydroxide solution. Extraction of the basic solution with chloroform and removal of the solvent from the dried chloroform extracts yields the crude product which when distilled in vacuo yields essentially pure 5-(3-dimethylaminopropylidene)-dibenzo[a/f ] [ 1,4] cycloheptatriene, BP 173°C to 177°C at 1.0 mm. 

Carboxylic acids don t give addition products with Grignard reagents because the acidic carboxyl hydrogen reacts with the basic Grignard reagent to... 

The simple hexaalkylditins, RsSnSnRs, do not disproportionate on heating, but, in oxolane (tetrahydrofuran) or acetonitrile in the presence of a base such as a Grignard reagent, or in the more strongly basic solvent hexamethylphosphoric triamide (HMPT), disproportionation readily occurs at room temperature, and, in HMPT, addition occurs to such alkynes as phenylacetylene and diphenylbutadiyne. The disproportionation is considered to proceed by nucleophilic attack upon tin (259, 260), e.g.,... 

Silyl-based linker 23, cleaved by either basic (TBAF) or neutral (CsF) fluoridolysis to release carboxylic acids, alcohols, or amines, was prepared by treatment of a Grignard reagent to an aldehyde resin [28], To demonstrate the utility of this handle, /)-bromobenzoic acid was... 

It is of interest to note that attachment of a basic side chain on carbon of an isomeric dibenzazepine affords a compound in which anticholinergic activity predominates, elantrine (50). Reaction of anthra-quinone (45) with the Grignard reagent from 3-chloro-N,N-dimethylaminopropane in THF in the cold results in addition to but one of the carbonyl groups to yield hydroxyketone 46. This is then converted to oxime 47 in a straightforward manner. Treatment of that intermediate with a mixture of phosphoric and polyphosphoric acids results in net dehydration of... 

---