And Grignard reactions

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

Among the most useful reactions of nitriles are hydrolysis to yield first an amide and then a carboxylic acid plus ammonia, reduction to yield an amine, and Grignard reaction to yield a ketone (Figure 20.3). 

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. 

In liquid-solid processes reaction takes place between a liquid reactant and an insoluble or sparingly soluble solid which must be finely divided to speed up the process. Another measure to accelerate the process is to use an aqueous solution of a phase-transfer agent (typically a quaternary ammonium salt). The solid can also be a catalyst for reactions between liquid components, e.g. in acylations, carried out both conventionally in the presence of metal chlorides (mostly AICI3) or catalysed by zeolites and Grignard reactions. 

There is still much to explore. For example, quantitative solid-state Wittig and Grignard reactions await exploration (see less than quantitative examples in [67]). First experiments are promising, but the authors did not yet care for running the reactions to completion or they did not assess the solid state even though interesting stereoselectivities emerged (review in [67]). 

R = CHj, R = and adenocarpine(16 R = CH=CHPh, R = H) ° are likewise dehydrogenated to 2,3 -bipyridine, and related dehydrogenation reactions afford substituted 2,3 -bipyridines. Ullmann and Grignard reactions have been used to synthesise 2,3 -bipyridine, whereas the Gomberg reaction of 3-pyridinediazonium chloride with pyridine and alkyl pyridines affords 2,3 -bipyridine, along with other isomeric bipyridines, and alkyl substituted 2,3 -bipyridines, respectively. " Photolysis of 3-... 

Instead of adding special equipment to individual production trains, it is also possible to place them centrally in the dry or wet section of the plant, respectively. In this way they can be connected as needed to different production trains. Another option is to create semispecihc production trains, For example, for hydrogenations, phosgenizations, Friedel-Crafts alkylations, and Grignard reactions. 

Alkyl-substituted ruthenocenes, preparation, 6, 635-636 Alkyl sulfonates, cross coupling, and Grignard reactions, 9, 44 Alkyltantalum imido complexes, as catalysts, 5, 193 Alkyl tellurides... 

Very frequently, Wittig and Grignard reactions are applied to the relevant ketones to generate the branch points in compounds such as 280 and 281.259... 

Unusual selectivity, however, is observed in the reduction (and Grignard reaction) of 6-phenyl- (e.g., 337a) and l,3-dibromothieno[c]tropylium salts which are exclusively attacked at C-4 or C-6, respectively (74YZ1452). In the tricyclic series, pyrrole 647 (Scheme 173) is reported to give a single reduction product [94JCS(P1)2579] whereas furoditropylium salt 260 forms... 

IV. Addendum on the Anomeric Configuration of /3-D-Glycopyranosylbenzenes. 282 V. Physical Properties of Products from Friedel-Crafts and Grignard Reactions 284... 

V. Physical Properties of Products from Friedel-Crafts and Grignard Reactions... 

The ability of Sml2 to reduce alkyl halides has been exploited in a number of carbon carbon bond-forming reactions. Radicals generated from the reduction of alkyl halides can be trapped by alkenes in cyclisation reactions to form carbocyclic and heterocyclic rings (see Chapter 5, Section 5.3), and the alkyl-samarium intermediates can be used in intermolecular and intramolecular Barbier and Grignard reactions (see Chapter 5, Section 5.4). The reduction of ot-halocarbonyl compounds with Sml2 gives rise to Sm(III) enolates that can be exploited in Reformatsky reactions (Chapter 5, Section 5.5) and are discussed in Section 4.5. 

A variety of functionalised organic halides have been found to be compatible with the Sml2-mediated Barbier and Grignard reactions. For example, ben-zyloxymethyl chloride can be used in conjunction with Sml2 for the alkoxy-methylation of ketones.120 This addition has been found to work well even for hindered ketones such as 101, an intermediate in White s 1987 approach to 2-desoxystemodinone (Scheme 5.70).121 It is important to note that, in contrast to analogous organometallics, decomposition via a-elimination is not observed. 

We can now extend our systematic analysis to problems involving alcohols and Grignard reactions. As examples, we consider the syntheses of an acyclic diol and a disubstituted cyclohexane, concentrating on the crucial steps that assemble the carbon skeletons and generate the final functional groups. 

Carbon-carbon bond formation is one of the oldest and most important topics of organic chemistry, and for a long time has been dominated by Friedel-Crafts and Grignard reactions. The former are based on stabilized carbocations as reagents and are exemplified by benzene alkylation (Equation 1), while the latter involve stabilized carbanions and are exemplified by acetone alkylation (Equation 2). 

Among the important reactions ofaitriles are hydrolysis.reduction, and Grignard reaction U> yield ketones tPigure 21.11k... 

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