Hi Sunil,

GRIGNARD REACTION In general terms, addition of Grignard reagent to Aldehydes and Ketones is known as the Grignard reaction. It is a reaction of a carbonyl compound with alkyl or arryl Magnesium/Zinc Halide to give an alcohol. Primary, Secondary or Tertiary alcohols may be prepared by the reaction of a suitable carbonyl-containing compound with an alkyl magnesium halide-so called Grignard reagent. The reagent is usually obtained quite readily by adding an alkyl halide to a suspension of magnesium turnings in anhydrous ethers. Initiation of the reaction may require the addition of a few crystals of iodine, the purpose of which may be to form a catalytic amount of Magnesium Iodide or possibly simply to etch the metal surface. As it is important that the iodine should be concentrated at the metal surface the mixture should not be stirred at this stage. Generally used solvents are THF, Dibutyl ether etc.

Formaldehyde gives primary alcohol, other Aldehydes give secondary alcohols, and Ketones give tertiary alcohols by this reaction. The reaction is of very broad scope, and hundreds of alcohols have been prepared by this reaction. The metal used generally is magnesium. But in general Besides Grignard reagents, alkyl-and aryl lithiums and alkyl zinc reagents are also used for attack of carbon on organo-metallic compounds. Organo-tin reagents, aryl lithium, titanium, alluminium are also employed

GR is used in Alkylation, in coupling reactions, for making Esters of Different Functional Groups, Aromatic & Tertiary Thiols etc

ACs like DMBC/DMBCA, DIMETOL, DAMASCONES etc are prepared by GR from many years. Diethyl ether is used as the solvent in many processes in spite of the potential hazards of flammability and formation of explosive peroxides. THF, Dibutyl ether and Diamyl ether have also been used, but these solvents present problems as well.

GR is becoming an important Industrial Process for many ACs productions now a days

Criticalities associated with the Grignard Reaction

Initiation of the reaction

Initiation of the reaction should occur within the first 10-20% addition of the RX solution in ethereal solvent. Evidence for the initiation is large exotherm and a visual change of the magnesium turnings from a bright shiny silver color to a dull gray black. Agitation should be strong enough to shear the magnesium turnings in the reaction mass. Until initiation has been confirmed, no more than 20% of the RX charge should be added to the reactor. Otherwise the large exotherm will release the reaction contents to the atmosphere.

Effect of moisture & Oxygen

Problems are homocoupled product, intra molecular reactions, formation of RMgO2X and noninitiated reaction. Proper manipulation and drying of each component must be carried out. Water in RX and Solvent and Mg must be less than 0.02% and free of Oxygen. Presence of water typically leads to the sudden initiation after all RX has been added. This takes place because the residual water is azeotroped out of the mixture during reflux Or is actually used up by residual Grignard reagent. To prevent this, dry the components properly and manipulate under nitrogen. Addition of small quantity of GR may help for the initiation.

Oxygen will react with GR to form RMgO2X. This peroxo-species can oxidize the other reactants, ligands and catalyst or final product. And the purification problems will arise.

RMgX + H2O ------------------------------à RH + MgX[OH]

Ether and non-polar Hydrocarbons are the generally used solvents, Solvent is selected for yield improvement, stereo chemical and regiochemical control and formation of dialkyl Mg species. The solvent effect is attributed to the solvent’s polarity, basicity, steric hindrance etc.

LIST OF SOME PERFUMERY & FLAVOUR PRODUCTS IN WHICH GRIGNARD REACTION IS USED

FREESIOL –H&R MATSUTAKE ALCOHOL -TAKASAGO (MORILLOL-BASF) UNDECAVERTOL -GIVAUDAN ROURE ALPHA DAMASCONE BETA DAMASCONE DELTA DAMASCONE BETA DAMASCENONE DYNASCONE-10-FIRMENICH DIHYDRO DAMASCONE PHENYL METHYL ETHYL CARBINOL ALPHA, ALPHA DIMETHYL PHENETHYL CARBINOL DIMETHYL BENZYL CARBINOL ACETATE IRONES DOREMOX-FIRMENICH FLOROSA-QUEST CLARYCET-IFF

Grignard reagent PhMgCl was added during the preparation of the catalyst system MgCl₂/di-n-butyl phthalate (DNBP)/TiCl₄ - AlEt₃/diphenyl dimethoxyl silane (DPDMS) to improve its performance. It was found that PhMgCl could enhance both the activity of the catalyst and the isotacticity of the products, but decreased the Ti content of the catalysts under the same preparation conditions. The polymerization kinetics showed that PhMgCl accelerates the decay in the same time that it increased the initial and final polymerization rates..

All the best....

why we can not use calcium other than Mg ?