Common Uses of Alkyl Halides

Classify the compound as a methyl, primary, secondary, or tertiary halide. 

Alkyl halides are used primarily as industrial and household solvents. C arbon tetrachloride (CCI4) was once used for dry cleaning, spot removing, and other domestic cleaning. Carbon tetrachloride is toxic and carcinogenic (causes cancer), however, so dry cleaners now use 1,1,1-trichloroethane and other solvents instead. 

Methylene chloride (CH2CI2) and chloroform (CHCI3) are also good solvents for cleaning and degreasing work. Methylene chloride was once used to dissolve the caffeine from coffee beans to produce decaffeinated coffee. Concerns about the safety of coffee with residual traces of methylene chloride prompted coffee producers to use liquid carbon dioxide instead. Chloroform is more toxic and carcinogenic than methylene chloride it has been replaced by methylene chloride and other solvents in most industrial degreasers and paint removers. 

Even the safest halogenated solvents, such as methylene chloride and 1,1,1-trichloroethane, should be used carefully, however. They are all potentially toxic and carcinogenic, and they dissolve the fatty oils that protect skin, causing a form of dermatitis. 

Many syntheses use alkyl halides as starting materials for making more complex molecules. The conversion of alkyl halides to organometallic reagents (compounds containing carbon-metal bonds) is a particularly important tool for organic synthesis. We discuss the formation of organometallic compounds in Section 10-8. 

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The synthesis of the cation is typically performed by alkylation of an amine, phosphine or sulfide, most commonly using an alkyl halide [ ]. In most cases the reaction is carried out with chloro-, bromo- and iodoalkanes as readily available alkylating reagents, with the reaction conditions becoming more gentle changing from chloride to bromide to iodide, as can be expected for nucleophilic substitution... 

Both reactants m the Williamson ether synthesis usually originate m alcohol pre cursors Sodium and potassium alkoxides are prepared by reaction of an alcohol with the appropriate metal and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4 7) thionyl chloride (Section 4 13) or phosphorus tri bromide (Section 4 13) Alternatively alkyl p toluenesulfonates may be used m place of alkyl halides alkyl p toluenesulfonates are also prepared from alcohols as their imme diate precursors (Section 8 14)... 

As depicted in Scheme 3.1, reductive and oxidative cleavages may follow either a concerted or a stepwise mechanism. RX is a commonly used designation for an alkyl halide. Many experimental studies of dissociative electron transfers have indeed taken as examples the reductive cleavage of alkyl halides. However, many other compounds have been investigated in the framework of reaction Scheme 3.1 in the organic and inorganic field, for reductions as well as for oxidations. 

The reaction of alkyl halides with silver nitrate constitutes an extremely useful method for the synthesis of high purity nitrate esters on a laboratory scale. ° The driving force for these reactions is the formation of the insoluble silver halide. Reactions have been conducted under homogenous and heterogeneous conditions. For the latter a solution of the alkyl halide in an inert solvent like benzene or ether is stirred with finely powdered silver nitrate. However, this method has been outdated and reactions are now commonly conducted under homogeneous conditions using acetonitrile as solvent. 

The prominent role of alkyl halides in formation of carbon-carbon bonds by nucleophilic substitution was evident in Chapter 1. The most common precursors for alkyl halides are the corresponding alcohols, and a variety of procedures have been developed for this transformation. The choice of an appropriate reagent is usually dictated by the sensitivity of the alcohol and any other functional groups present in the molecule. Unsubstituted primary alcohols can be converted to bromides with hot concentrated hydrobromic acid.4 Alkyl chlorides can be prepared by reaction of primary alcohols with hydrochloric acid-zinc chloride.5 These reactions proceed by an SN2 mechanism, and elimination and rearrangements are not a problem for primary alcohols. Reactions with tertiary alcohols proceed by an SN1 mechanism so these reactions are preparatively useful only when the carbocation intermediate is unlikely to give rise to rearranged product.6 Because of the harsh conditions, these procedures are only applicable to very acid-stable molecules. 

Nitriles may be prepared by several methods (1). The first nitrile to be prepared was propionitrile, which was obtained in 1834 by distilling barium ethyl sulfate with potassium cyanide. This is a general preparation of nitriles from sulfonate salts and is referred to as the Pelouze reaction (2). Although not commonly practiced today, dehydration of amides has been widely used to produce nitriles and was the first commercial synthesis of a nitrile. The reaction of alkyl halides with sodium cyanide to produce nitriles (eq. 1) also is a general reaction with wide applicability ... 

Besides new insight into the reactivity of free radicals, methods for die production of carbon-centered free radicals have also seen major improvements in die last several years. One very common new mediod is to use tin-based reagents as radical chain carriers. Trialkyltin radicals readily abstract bromine or iodine from carbon to produce a carbon-centered free radical. Placement of a bromide or iodide substituent on a substrate dius permits formation of a carbon-centered free radical at diat position using tin-based mediodology. This process was initially developed for die reduction of alkyl halides, and it remains an excellent synthetic method for diat purpose. The complete chain mechanism for die reduction is shown. 

The term stereoselective is often confused with the term stereospecific, and the literature abounds with views as to the most satisfactory definition. To offer some clarification, it is perhaps timely to recall a frequently used term, introduced a decade or so ago, namely the stereoelectronic requirements of a reaction. All concerted reactions (i.e. those taking place in a synchronised process of bond breaking and bond forming) are considered to have precise spatial requirements with regard to the orientation of the reactant and reagent. Common examples are SN2 displacement reactions (e.g. Section 5.10.4, p. 659), E2 anti) elimination reactions of alkyl halides (e.g. Section 5.2.1, p.488), syn (pyrolytic) elimination reactions (Section 5.2.1, p.489), trans and cis additions to alkenes (e.g. Section 5.4.5, p. 547), and many rearrangement reactions. In the case of chiral or geometric reactants, the stereoisomeric nature of the product is entirely dependent on the unique stereoelectronic requirement of the reaction such reactions are stereospecific. 

The E2 elimination occurs with a strong base (like a hydroxide or ethoxide ion) in a protic solvent (like ethanol or water). The E2 reaction is more common than the El elimination and more useful. All types of alkyl halide can undergo the E2 elimination and the method is useful for preparing alkenes. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

One common present day preparation of dialkyl mono-and ditellurides involves the reaction of alkyl halides with alkali metal tellurides that have been prepared in situ. The reactions are commonly carried out in aqueous or nonaqueous solutions. Solutions of sodimn in liquid ammonia also provide a useful media for the reduction of tellurium. ... 

Reductive dehalogeuation of alkyl halides. Lithium aluminum hydride has commonly been used only for reductive dchalogenation of reactive substrates organotin hydrides, for example tri- -btityltin hydride (I. 1192-1193 2, 424 3, 294), have been used for reduction of inert halides. Recently JeflToid ei al. have reported that supposedly inert halides are reducible by lithium aluminum hydride. Thus the vinyl halide (I) is reduced to (2, endb-2-phenylbicyclo[3.2. l]octene-3) by lithium aluminum hydride in refluxing ether (24 hr.). 3-Bromobicyclo[3.2.l]octene-2 is reduced to the parent... 

The coupling of alkyl halides by treatment with sodium to give a symmetrical product is called the Wurtz reaction. Side reactions (elimination and rearrangement) are so common that the reaction is seldom used. Mixed Wurtz reactions of two alkyl halides are even less feasible because of the number of products obtained. A somewhat more useful reaction (though still not very good) takes place when a mixture of an alkyl and an aryl halide is treated with sodium to give an alkylated aromatic compound (the Wurtz-Fittig reaction)... 

Of these other compounds, alkyl esters of sulfonic acids, ArS020R, are most commonly used in place of alkyl halides usually in the study of reaction mechanisms. but also in synthesis. As the anions of strong acids, sulfonate anions are weak bases and hence are good leaving groups in either nucleophilic substitution or. elimination ... 

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