Grignard reagents making

The use of the same halide in the diorgano tellurium dihalide and the Grignard reagent makes halogen exchange reactions during the isolation procedures unnecessary3. 

In Wakefield s view, the solvation of the Grignard reagent makes both the Mg—C and the Mg—bonds less stable, thereby increasing the reactivity of the carbon atom and favouring the formation of the solvated RMg ion. The latter is more reactive than the undissociated molecule in both electrophilic and nucleophilic reactions. An increase in the solvating ability of the solvent beyond a certain limit, however, leads to the stabilization of the solvate of RMg" and thus to its lower reactivity. It can be seen that the above considerations may be employed to explain both a decrease and an increase in reactivity, but they are unsuitable for a prediction of the tendency and nature of the solvent effect. 

The preparation of the bromobenzodioxole or bromobenzene is going to be the same no matter which one is used and no matter which precursor the chemist wishes to make. This means that this first part needs to be done correctly. This first part of preparation that Strike is talking about is the creation of a Grignard reagent out of the bromo compound starting material [125,131-134]. Mr. Grignard earned a Nobel prize for this in 1912 so you can bet that it s a pretty good procedure. 

In contrast to alcohols with their nch chemical reactivity ethers (compounds contain mg a C—O—C unit) undergo relatively few chemical reactions As you saw when we discussed Grignard reagents m Chapter 14 and lithium aluminum hydride reduc tions m Chapter 15 this lack of reactivity of ethers makes them valuable as solvents m a number of synthetically important transformations In the present chapter you will learn of the conditions m which an ether linkage acts as a functional group as well as the methods by which ethers are prepared... 

In terms of cost, the effectiveness of the catalytic cycle in the ring closure makes this process economical in palladium. The first three steps in the reaction sequence -- ring opening of an epoxide by a Grignard reagent, converison of an alcohol to an amine with inversion, and sulfonamide formation from the amine — are all standard synthetic processes. 

One approach (.40) has been to conduct the reaction in the presence of a more electropositive metal, often as an alloy. In the presence of magnesium, tin reacts with ethyl bromide to give tetraethyl tin, and various additives promote the reaction, the sequence of effectiveness being carbitols I > tetrahydrofuran, tetrahydrothiophene > ether triethylamine Br the ions ClOj, PFg, BFj, and BPhj are without effect. It is suggested that this reflects the coordination of the additive (L) to the Grignard reagent that is first formed, making it more reactive towards metallic tin. 

The same two disconnections on TM (9) suggests (b) as the better route, Grignard reagent (12) might be difficult to make, but ester (13) is a simple 1,2-diX problem. 

Problem Alcohol (14) was needed to make the corresponding Grignard reagent.Suggest a synthesis guided by branch-point disconnect ions. 

The ketone 15 was eventually prepared by Grignard addition to Weinreb amide 21, as shown in Scheme 5.5. The Weinreb amide 21 was prepared from p-iodobenzoic acid (20). The phenol of readily available 3-hydroxybenzaldehyde (22) was first protected with a benzyl group, then the aldehyde was converted to chloride 24 via alcohol 23 under standard conditions. Preparation of the Grignard reagent 25 from chloride 24 was initially problematic. A large proportion of the homo-coupling side product 26 was observed in THF. The use of a 3 1 mixture of toluene THF as the reaction solvent suppressed this side reaction [7]. The iodoketone 15 was isolated as a crystalline solid and this sequence was scaled up to pilot plant scale to make around 50 kg of 15. 

Organomagnesium reagents, which can serve as the nucleophiles in the Kumada coupling, are easy to make and many of them are commercially available. Even though some Kumada reactions can be run at room or lower temperature, many functional groups are not tolerant of Grignard reagents. Nonetheless, in the synthesis of thienylbenzoic acid 24, the carboxylic acid moiety did survive the reaction conditions [25],... 

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