Halides synthesis from active

A superior and relatively versatile procedure for the synthesis of unsymmetrical dialkyl thioethers, which avoids the unattractive direct use of thiols, utilizes the stable l-alkylthioethaniminium halides, which are readily obtained from thioacet-amidc [32] (Scheme 4.4). The reaction has also been used for the synthesis of alkyl aryl thioethers from activated aryl halides [33], but it cannot be used for the synthesis of cyclic thioethers, as polymeric sulphides are formed from a,co-dihaloalkanes. A similar sequence to that which leads to the thioethers has been used for the synthesis of S-alkyl thioesters [34] (see 4.1.26). 

In the unconventional synthesis of thioethers (Scheme 4.11), cyanide ion is displaced from thiocyanates by carbanions [52, 53], which have been generated under phase-transfer catalytic conditions (cf. 4.1.12). Thiocyanates are readily obtained by a standard catalysed nucleophilic substitution reaction [4, 54-58] (see Table 4.19). Aryl thiocyanates are obtained from activated aryl halides [4, 57] (see Chapter 2). 

Recently, catalyst 50 (n > 4) was reported highly active and selective for olefin synthesis from alkyl halides with aqueous sodium or potassium hydroxide without the formation of by-product alcohols 172). The active catalyst structures were suggested to involve self-solvated polymeric alkoxides 173) 52 and/or complexed hydroxides 53. 

The synthesis of organozinc compounds by electrochemical processes from either low reactive halogenated substrates (alkyl chlorides) or pseudo-halogenated substrates (phenol derivatives, mesylates, triflates etc.) remains an important challenge. Indeed, as mentioned above, the use of electrolytic zinc prepared from the reduction of a metal halide or from zinc(II) ions does not appear to be a convenient method. However, recent work reported by Tokuda and coworkers would suggest that the electroreduction of a zinc(II) species in the presence of naphthalene leads to the formation of a very active zinc capable of reacting even with low reactive substrates (equation 23)11. 

Ring synthesis from non-heterocycles by closure y to the heteroatom are reported. Sulfonium ylides (135) with active methylene compounds such as malononitrile give a C-phenacyl product (136) however, when reacted with /3-diketones and /3-ketonic esters they produce furans quantitatively (74CL101). In these cases O-phenacylation takes place followed by cyclization to give the 3-hydroxydihydrofuran (137), which is dehydrated to the furan (138) (Scheme 30). These furans differ from those formed by the reaction of the diketone or ketonic esters with phenacyl halides. The latter reaction takes place by C-phenacylation, yielding the isomeric furans (139). 

Amino acid synthesis (8, 389). Alkylation of the aldimine (1) from glycine ethyl ester and /j-chlorobenzaldehyde under phase-transfer conditions offers a general route to amino acids. Either liquid-liquid phase-transfer or solid-liquid phase-transfer catalytic conditions are satisfactory with active halides, but alkylation with allylic halides and less active alkyl halides is best effected under ion-pair extraction conditions (6,41), with 1 equiv. of tetra-n-butylammonium hydrogen sulfate (76-95% yields).1... 

Benzotriazoles, for example, are accessible from o-aminoaryl-substituted triazenes after a two-step reaction sequence a nucleophilic displacement followed by cleavage/heterocyclization.35 The nucleophilic halide displacement of activated haloarenes is an indispensable tool for the synthesis of highly substituted arenes. Fluoronitroarenes in particular have served as excellent precursors in this transformation. Thus, it was appealing to combine this SNAr reaction with the flexibility of diazonium chemistry. In this case, an immobilized fluoronitrophenyl triazene would be the equivalent of the Sanger reagent. 

In 1995, Beletskaya [34] and Collum [35] reported independently the application of alkyltrichlorostannanes instead of tetraorganotin compounds, overcoming the disadvantage of three inert anchoring groups ( atom economy ) and technologically more important, because of their lower toxicity and availability via economic direct synthesis from tin(II) compounds [36], Furthermore, the hydrolysis of the tin-halide bond in water results in higher water-solubility, activation of the C—Sn bond toward electrophiles (e.g., in transmetallation) and less toxic by-products. The reaction may be accomplished via intermediate anionic hydroxo complexes [37], produced in situ in aqueous alkaline solution, and proceeds in most cases in 3 h at 90-100°C (Eq. 12). 

Now let s use alkoxides to make ethers—the Williamson ether synthesis. Several modifications of the original procedure have made this venerable method quite useful, although there are some restrictions. The reaction works only for alkyl halides that are active in the Sn2 reaction. Therefore, tertiary halides cannot be used. They are too hindered to undergo the crucial Sn2 reaction. Sometimes there is an easy way around this problem, but sometimes there isn t. For example, tert-huXy methyl ether cannot be made from tert-hnty iodide and sodium methoxide, but it can be made from / r/-butoxide and methyl iodide (Fig. 7.106). However, there is no way to use the Williamson ether synthesis to make di-Z rZ-butyl ether. 

Table 1 Synthesis of arylcalcium halides via direct synthesis from haloarene and activated calcium powder...

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