Reaction with alkyl halides to form

The reduction of benzoic acids affords the dienolate (77) which may be alkylated in situ by a variety of electrophiles to afford 1-substituted derivatives. Clearly, the addition of alcohol must be avoided or limited to small quantities. It may also be necessary to remove the ammonia before adding the electrophile. The vast majority of applications have been based on reactions with alkyl halides to form (78), but additions of (77) to formaldehyde, epoxides and a,p-unsaturated esters to form the range of adducts (79) to (81) have also been reported (Scheme 14). 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

Preparation of alkyl azides.1 Because it is easy to prepare, stable, and soluble in low-boiling organic solvents such as CHC13, it is the reagent of choice for reaction with alkyl halides to form the corresponding alkyl azides in yields of 60-96%. With the more reactive alkyl halides, in particular alkyl bromides, the reaction is... 

Enolates react with alkyl halides to form a new CC bond. A mixture of stereoisomers may result. For example, each of the reactions shown below gives two products, with the major product constituting > 90% of the mixture. 

Triphenylphosphine reacts with alkyl halides to form alkyltriphenylphosphonium salts. Upon reaction with strong bases, the salts release a proton to form an ylide (alkylidenetriphenylphosphorane), which is capable of reacting with aldehydes or ketones providing an unambiguous route to olefins. Since there are virtually no... 

Reactions with cyclopropene.11 Lithium organocuprates react with the cyclo-propenone ketal 1 (12, 152-154) to form a copper species (a) that behaves as an enolate of a cyclopropanone. Thus it reacts with alkyl halides to form cis-2,3-disubstituted derivatives of 1. 

Frankland s method orgchem Reaction of dialkyl zinc compounds with alkyl halides to form hydrocarbons may be used to form paraffins containing a quaternary carbon atom. frarik-lonz, meth-3d ... 

The general reactions of the compounds are much as expected. They react with strong reducing agents to give ammonia and amines, with complete destruction of the complexes.143-14 The halides are labile and can be substituted.144 The compounds react with acids to form alkylhydrazido complexes,148 and with alkyl halides to form dialkylhydrazido(2 —) complexes, in reactions which are typical SN2 reactions,149 though electrophilic attack (viz. by Me+) is also a possibility.150... 

Lead alloys other than sodium-lead alloy are also reactive with alkyl halides to form R4Pb compounds. Dimagnesium-lead alloy, Mg2Pb, is reactive with alkyl halides in the presence of a diethyl ether-iodine catalyst mixture to form R4Pb 285>. The reaction with ethyl chloride was considered at one time for the commercial production of tetraethyllead, but the high yields obtained in the laboratory could not be duplicated in pilot plant equipment 284>. A main advantage of the use of Mg2Pb in place of NaPb is that no by-product lead metal is formed under ideal conditions. 

The reaction of metals with alkyl halide to form alkylmetal compounds is typical for lithium and magnesium. This so-called direct synthesis was applied to the preparation of both cyclopropyllithium" and derivatives and cyclopropylmagnesium halides under the standard preparative conditions of Grignard reagents without ring cleavage (equation 1). 

Sodium thiosulfate reacts with alkyl halides to form salts of the type RSSOjNa (Bunte salts). Alkyl disulfides may be obtained from these salts by pyrolysis or reaction with iodine or hydrogen peroxide. The yields range from 47% to 6S>%. Cyano and carboxyl groups do not interfere. Benzoylation of sodium thiosulfate produces benzoyl disulfide in 58% yield. ... 

Thiazoles react readily with alkyl halides to form the corresponding thiazolium salts. Many examples exist in the literature and studies of the effect of thiazole ring substituents upon the rate of reaction have been well reviewed < 1984CHEC(6)235>. Thiazoles and benzothiazoles substituted with a hydroxy, thio, or amino group can undergo alkylation equally at either the endo- or exocyclic heretoatom. This reactivity has been discussed elsewhere < 1996CHEC-II(3)373>. 

In the presence of sodium hydroxide, thiols react with alkyl halides to form the sulfides (20) the reaction occurs via the sodium thiolate and is analogous to the well-known Williamson synthesis of ethers and can also be applied to obtain unsymmetrical sulfides (Scheme 18). Symmetrical sulfides may be prepared directly by condensation of sodium sulfide with alkyl halides (Scheme 18). These reactions are of the SN2 type, and consequently the optimum yields of sulfides are realised using primary alkyl halides. 

Sulfides contain a nucleophilic sulfur atom and consequently undergo important reactions involving the lone electron pairs on sulfur thus, they react with alkyl halides to form... 

The electron-withdrawing properhes of the phosphoryl group were explored and exploited in the very earliest studies. In 1927, A.E. Arbuzov and Dunin reported a study of the reacrion of diethyl l-(ethoxycarbonyl)methylphosphonate with sodium or potassium metal and showed that a-metallated phosphonate produets react with alkyl halides to form a-substituted phosphonoacetates. This approach not only complemented the Michaelis-Arbuzov reaction but also provided access to a more diversified range of phosphonates. The development of phosphonate carbaiuons became more sophisticated with the introduction of powerful bases such as NaH and NaNHj and hthium reagents. Subsequently, two major synthetic advances revolutionized phosphonate chemistry. 

The sulfur analogs of ethers are called sulfides or thioethers. Sulfur is an excellent nucleophile because its electron cloud is polarizable (Section 10.3). Sulfides, therefore, react readily with alkyl halides to form sulfonium salts—a reaction that an ether cannot undergo because oxygen is not as nucleophilic and cannot accommodate a charge as easily. 

The primary amines unite with alkyl halides to form salts of secondary and tertiary amines and of the quarternary ammonium bases, the reactions being analogous to those already described in connection with the aliphatic amines. Like the latter they are converted into isocyanides when warmed with potassium hydroxide and an alcoholic solution of chloroform. 

Alkenes undergo electrophilic addition reactions with hydrogen halides, to form alkyl halides. 

Diphosphines are weakly basic, but reaction with strong adds usually leads to breaking of the P-P bond (6.670), although there is no reaction with (F3C)2p-P(CF3)2 up to at least SOO C. Most tetraalkyl diphosphines react with alkyl halides to form a phosphonium salt (6.671), but tetracyclohexyl diphosphine cleaves to give a mixture of phosphines (6.672). 

N. Menschutkin, Z Physik. Chem. 5, 589 (1890) 6,41 (1890). Reaction of tertiary amines with alkyl halides to form quaternary salts ... 

Triphenylphosphine reacts with alkyl halides to form phospho-nium salts. Organolithium bases react with alkyltriphenylphos-phonium salts to give phosphorus ylids, which react with aldehydes and ketones to give alkenes in what is known as the Wittig reaction. 

Other synthetic applications for the alkanolamines include the reaction of a monoalkanolamine with aldehydes and ketones to give Schiff bases [3], reaction of alkyl halides to form N-alkyl derivatives, and reaction of epoxies to form mixed alkanolamines [4]. 

The propagation steps of these chain reactions are given in Scheme 12, which represents a plausible mechanistic rationalization of the results. That is, Bu Sn radical, initially generated by photolysis of ditin, reacts with alkyl halide to form an alkyl radical that attacks the allyl sulfide (Sh2 process) to give the desired product and thiyl radical. The displacement reaction from ditin gives the Bu Sn radical, thus completing the cycle of this chain reaction. An intramolecular version of this process (equation (43)) has been introduced by Ueno et ai [89a] and later applied by Boger and Wysocki as a key step in multistep synthesis of some natural products [89b]. 

Thioethers react with alkyl halides to form sulfonium salts, which have excellent leaving groups, so they undergo substitution reactions with ease. 

When we discussed elimination reactions in Chapter 5 we learned that a Lewis base can react with an alkyl halide to form an alkene In the present chapter you will find that the same kinds of reactants can also undergo a different reaction one m which the Lewis base acts as a nucleophile to substitute for the halo gen substituent on carbon... 

Anions of acetylene and terminal alkynes are nucleophilic and react with methyl and primary alkyl halides to form carbon-carbon bonds by nucleophilic substitution Some useful applications of this reaction will be discussed m the following section... 

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