Grignard reaction: alkylation

By using a lOOX excess of the metal (less than lOO for experiments on a large scale) one can save much time. Some Grignard reactions, especially those with tertiary alkyl chlorides and cyclohexyl chloride, are not easily started and it seemed desirable, therefore, to inform the user of this book about our experiences. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

Phosphorus—hydrogen compounds undergo a metathetical exchange with some organometallic alkylating reagents (see Grignard reactions) ... 

Historically, among the most important reactions of siUcon haUdes are those occurring with metal alkyls and metal alkyl haUdes. The Grignard reaction, for example, was the first commercial process for manufacturing organosiUcon compounds, which were later converted to siUcones (19). 

All lation. Thiophenes can be alkylated in the 2-position using alkyl halides, alcohols, and olefins. Choice of catalyst is important the weaker Friedel-Crafts catalysts, eg, ZnCl2 and SnCl, are preferred. It is often preferable to use the more readily accompHshed acylation reactions of thiophene to give the required alkyl derivatives on reduction. Alternatively, metalation or Grignard reactions, on halothiophenes or halomethylthiophenes, can be utilized. 

Excess alkylating reagent is required if the tetraorganotin is desired as the exclusive product. In commercial practice, the stoichiometry is kept at or below 4 1, since the cmde product is usually redistributed to lower organotin chlorides in a subsequent step and an ether is used as the solvent (86). The use of diethyl ether in the Grignard reaction has been generally replaced with tetrahydrofuran. 

Reactions of titanium alkyls with aldehydes and ketones are generally more stereospecific and selective than the corresponding Grignard reactions (416). 

Cadmium alkyl and aryl halides, RCdX, as weU as cadmium allyls have been prepared by Grignard reactions but, as yet, have not realized any commercially important uses despite reactivity toward a number of organic and inorganic materials. 

Cesium forms simple alkyl and aryl compounds that are similar to those of the other alkah metals (6). They are colorless, sohd, amorphous, nonvolatile, and insoluble, except by decomposition, in most solvents except diethylzinc. As a result of exceptional reactivity, cesium aryls should be effective in alkylations wherever other alkaline alkyls or Grignard reagents have failed (see Grignard reactions). Cesium reacts with hydrocarbons in which the activity of a C—H link is increased by attachment to the carbon atom of doubly linked or aromatic radicals. A brown, sohd addition product is formed when cesium reacts with ethylene, and a very reactive dark red powder, triphenylmethylcesium [76-83-5] (C H )2CCs, is formed by the reaction of cesium amalgam and a solution of triphenylmethyl chloride in anhydrous ether. 

Aluminium alkyls Chromic oxide Alkylations/Grignard reactions Acute thermal burns, lung damage Cr may be converted to the more toxic and carcinogenic Cr ... 

Grignard reaction is the use of alkyl magnesium halides to form a host of products by reaction with a variety of chemicals... 

The alkaloids cotamine (259), hydrastinine (261), and berberinal (260), each possessing a grouping formed by interaction of an aldehyde with a secondary amino group in their molecule, are unusual. The Grignard reaction of free base 166 does not occur as readily as that of the corresponding salt 167. Both reactions lead to the alkylated product 168. For example, only 50% of hydrastinine reacts and 50% is regenerated, whereas hydrastinine hydrochloride reacts almost quantitatively (261). The salt undoubtedly contains a C=N double bond. In the case of the free base, the presence of a C=N double bond was not proven, and the reaction probably occurs by direct cleavage of the C—OH bond. 

Thus the diazirines could be related by a smooth reaction to a well investigated class of compounds. The three-membered ring structure of the diazirines was thus largely confirmed. They can be obtained from compounds which certainly have a three-membered ring structure [Eq. (54)] and are easily convertible into compounds which have equally well confirmed three-membered ring structures. The structure of the 1-alkyl-diaziridines (43) obtained by the Grignard reaction were confirmed by identification with known compounds, usually prepared by the reaction of Schiff s bases with chloramine [Eq. (32)]. The results of some of these reactions are collected in Table XII. 

Another type of Grignard reaction is the alkylation with alkyl halides. Upon treatment of a Grignard reagent RMgX with an alkyl halide 5, a Wwrtz-like coupling reaction takes place. 

Similarly, the reaction of the parent thiirane dioxide, the 2-chloro- and 2,3-cis-dimethylthiirane dioxides with either Grignard or alkyl lithium reagents, has been studied extensively. The fair-to-good yields of the sulfinates (62) obtained (48-82%), accompanied by ethylene (or the corresponding alkenes for substituted thiirane dioxide), have been interpreted in terms of initial nucleophilic attack of the base on the sulfur atom as depicted in equation 17116. 

Many pharmacologically active compounds have been synthesized using 5-bromoisoquinoline or 5-bromo-8-nitroisoquinoline as building blocks.6 7 8 9 10 11 The haloaromatics participate in transition-metal couplings 81012 and Grignard reactions. The readily reduced nitro group of 5-bromo-8-nitroisoquinoline provides access to an aromatic amine, one of the most versatile functional groups. In addition to N-alkylation, TV-acylation and diazotiation, the amine may be utilized to direct electrophiles into the orthoposition. 

Organomercury compounds undergo a similar reaction. Alkyl and aryl Grignard reagents can be converted to carboxylic esters with Fe(CO)5 instead of CO. Amides have been prepared by the treatment of trialkyl or triarylboranes with CO and an imine, in the presence of catalytic amounts of cobalt carbonyl ... 

Liquid-solid reactions (Friedel-Crafts acylations and alkylations, Grignard reactions) 1-5 50-250 250 250... 

The same authors also observed that 25 underwent a Grignard reaction which provided a new route for synthesizing various 5-alkyl or 5-aryl derivatives of benzo[6]thiepin (27) 22). 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

One of the most common types of reactions carried out to prepare organic derivatives of the group IVA elements is that of transferring an alkyl group by means of a Grignard reagent. Alkylation of SnCl4 can be illustrated as follows ... 

This type of reaction involves both oxidation and addition of groups, so it is known as an oxad reaction. Alkyl derivatives of PC13 can be prepared by the reactions with Grignard reagents and metal alkyls illustrated in the following equations ... 

Alternatively, trialkyltinmagnesium halides47, prepared by a Grignard reaction using either alkyl bromides or chlorides, can be hydrolysed to give deuterated or tritiated tin hydrides (equation 43). 

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