Reactivity, alkyl halides with ethanol

The acaricide (kills mice and ticks) chlorbenside 43 is disconnected to give an acidic thiophenol 44 and a reactive alkyl halide 25. The synthesis merely combines these two in ethanol with NaOEt as base.6... 

Diethyl ether is prepared commercially by intermolecular dehydration of ethanol with sulfuric acid. The Williamson ether synthesis, another route to ethers, involves preparation of an alkoxide from an alcohol and a reactive metal, followed by an SN2 displacement between the alkoxide and an alkyl halide. 

Ben2 yl-type chlorides are converted to the corresponding cyanides much more rapidly (85-90%). Ring substituents include alkyl, halo, carbethoxy and nitro groups. The more reactive benzyl halides, particularly the p-methoxy derivatives, are subject to extensive alcoholysis when ethanol is employed as the solvent. The successful use of acetone, acetonitrile, and phenylacetonitrile as solvents has been described. Conversion by cuprous cyanide and pyridine has been successfully applied to benzyl chloride as well as to di-o-tolylchloro-methane. It is interesting to find that treatment of a-chloroethylbenzene, C,H,CH(C1)CH, with cuprous cyanide gives 1,3-diphenyI-l-butene,... 

Alkyl halides in the presence of a zinc-copper couple, as a mixture of zinc dust and copper(i) iodide, reacted smoothly with a-enones and a-enals in aqueous media (Scheme 4.7). Sonication enhanced the efficiency of the process, leading to 1,4 adduct in good yields (Petrier et al, 1986). Such a conjugate addition was later extended to various electron-deficient alkenes, including a,P-unsaturated esters, amides, nitriles (Dupuy et al., 1991) or phosphine oxides (Pietrusiewicz and Zablocka, 1988). It appeared that the reactivity of the halide (RX) followed the order tertiary > secondary primary and iodide > bromide chloride. The preferred solvent system was aqueous ethanol, but the parameter of highest importance was the solvent composition (Luche and Allavena, 1988a). 

With the use of these sensitivity-enhancement approaches the stable alkoxide intermediates were indeed detected by C CP/MAS NMR spectroscopy. Isopropoxide was the first alkoxy intermediate reliably identified in propylene labeled with C in the CH= group) conversion on zeolite HY [15]. Isopropoxide exhibits the signal at 87 ppm from the labeled C atom, which is characteristic of the (CH3)2CH fragment bonded to an oxygen atom of the zeolite framework (Fig. 20). Later, other alkoxide intermediates were detected and characterized. It was demonstrated that methoxides [121,122] and ethoxides [122,123] formed from methyl and ethyl iodides and also from methanol and ethanol on H-ZSM-5 and CsX zeolites. Isobutoxy [124] and tert-butoxy [90] intermediates resulted from the dehydration of isobutanol and tert-butanol on HZSM-5. Alkoxides are highly reactive species. For example, surface methoxides are effective methylating agents in their reactions with methanol, water, ammonia, alkyl halides, HCl, CO, acetonitrile, and aromatic compounds [125]. 

Complexation with zinc effectively separates the C3S5 dianion from the trithiocarbonate ion in high yield, and the material obtained is sufficiently pure for further reactions. The quaternary ammonium zincate salt is alkylated slowly but smoothly by many halides at room temperature in solvents such as acetone or tetrahydrofuran. Reaction of the zincate with benzoyl chloride followed by cleavage of the resulting benzoate by sodium ethoxide in ethanol provides the much more reactive species NajCaSs. The sodium salt is, however, very air sensitive,5 whereas the zinc salt is completely stable. 

A difficulty sometimes encountered in the alkylation of active methylene compounds is the formation of unwanted dialkylated products. During the alkylation of the sodium salt of diethylmalonate, the monoalkyl derivative formed initially is in equilibrium with its anion. In ethanol solution, dialkylation does not take place to any appreciable extent because ethanol is sufficiently acidic to reduce the concentration of the anion of the alkyl derivative, but not that of the more acidic diethylmalonate itself, to a very low value. However, replacement of ethanol by an inert solvent favours dialkylation. Dialkylation also becomes a more serious problem with the more acidic cyanoacetic esters and in alkylations with very reactive electrophiles such as allyl or benzyl halides or sulfonates. 

Much of the reactivity of amido ligands involves proton exchange processes that eliminate amine. The exchange is believed to occur by an associative mechanism consequently, the rate of reaction decreases for sterically congested metal complexes. For example, treatment of V[N(CH3)2]j with terf-butanol at room temperature forms V(O-f-Bu) in good yield, while at this temperature the more encumbered complex W[N(CH3)2] reacts only slowly with methanol and ethanol, and not at all with tert-butanoV° The use of bulky N-alkyl substituents allows for the isolation of low-coordinate complexes, such as Cr[N( -Pr)2]3- Amido complexes derived from primary amines can also serve as precursors to imido complexes. In many cases, amido halide complexes form imido complexes by loss of hydrogen chloride in the presence of a base (Equation 4.17). ... 

---