Catalytic reactions alkyl halides

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

Triflates of aluminum, gallium and boron, which are readily available by the reaction of the corresponding chlorides with triflic acid, are effective Fnedel-Crafis catalysis for alkylation and acylation of aromatic compounds [119, 120] Thus alkylation of toluene with various alkyl halides m the presence of these catalysts proceeds rapidly at room temperature 111 methylene chloride or ni-tromethane Favorable properties of the triflates in comparison with the correspond mg fluorides or chlorides are considerably decreased volatility and higher catalytic activity [120]... 

A better method for preparing primary amines is to use the azide synthesis, in which azjde ion, N3, is used for SN2 reaction with a primary or secondary alkyl halide to give an alkyl azide, RN3. Because alkyl azides are not nucleophilic, overalkylation can t occur. Subsequent reduction of the alkyl azide, either by catalytic hydrogenation over a palladium catalyst or by reaction with LiAlK4. then leads to the desired primary amine. Although the method works well, low-molecular-weight alkyl azides are explosive and must be handled carefully. 

Fewer examples are reported for organic electrode reactions some alkyl halides were catalytically reduced at electrodes coated with tetrakis-p-aminophenylporphy-rin carboxylate ions are oxidized at a triarylamine polymer and Os(bipy)3 in a Nafion film catalytically oxidizes ascorbic acid Frequently, modified electrodes fail to give catalytic currents for catalyst substrate combinations that do work in the homogeneous case even when good permeability of the film is proven... 

Amides are very weak nucleophiles, far too weak to attack alkyl halides, so they must first be converted to their conjugate bases. By this method, unsubstituted amides can be converted to N-substituted, or N-substituted to N,N-disubstituted, amides. Esters of sulfuric or sulfonic acids can also be substrates. Tertiary substrates give elimination. O-Alkylation is at times a side reaction. Both amides and sulfonamides have been alkylated under phase-transfer conditions. Lactams can be alkylated using similar procedures. Ethyl pyroglutamate (5-carboethoxy 2-pyrrolidinone) and related lactams were converted to N-alkyl derivatives via treatment with NaH (short contact time) followed by addition of the halide. 2-Pyrrolidinone derivatives can be alkylated using a similar procedure. Lactams can be reductively alkylated using aldehydes under catalytic hydrogenation... 

Efforts to improve the efficient synthesis of organocadmium complexes by reaction of elemental cadmium with alkyl halides have been reported. Recent studies show that the presence of catalytic amounts of Cul and BuMgl in the reaction of alkyliodides with cadmium metal allows for the formation of 172a-c in high yield and high purity (Equation (58)).241... 

A related example involves the N-alkylation of azaheterocycles such as imidazole (Scheme 4.8). These reactions are typically performed using 1.5 equivalents of the alkyl halide and a catalytic amount of tetrabutylammonium bromide (TBAB). The reactants are adsorbed either on a mixture of potassium carbonate and potassium hydroxide or on potassium carbonate alone and then irradiated with microwaves (domestic oven) for 0.5 to 1 min. With benzyl chloride, a yield of 89% was achieved after 40 s [18]. 

The concept of performing microwave synthesis in room temperature ionic liquids (RTIL) as reaction media has been applied to several different organic transformations (Scheme 4.18), such as 1,3-dipolar cycloaddition reactions [54], catalytic transfer hydrogenations [55], ring-closing metathesis [56], the conversion of alcohols to alkyl halides [57, 58], and several others [59-61],... 

N-Substituted amides and lactams can be rapidly N-alkylated under solid-liquid PTC conditions by use of microwave irradiation. The reactions were performed simply by mixing an amide with 50% excess of an alkyl halide and a catalytic amount of TBAB. These mixtures were absorbed on a mixture of potassium carbonate and potassium hydroxide [41] and then irradiated in an open vessel in a domestic micro-wave oven for 55-150 s (Eq. 28). 

A typical phase transfer catalytic reaction of the liquid/liquid type is the cyanation of an alkyl halide in an organic phase using sodium or potassium cyanide in an aqueous phase. When these phases are stirred and heated together very little reaction occurs. However, addition of a small amount of crown ether (or cryptand) results in the reaction occurring to yield the required nitrile. The crown serves to transport the cyanide ion, as its ion pair with the complexed potassium cation, into the organic phase allowing the reaction to proceed. 

The second pathway is represented by Eqs. (8)—(11). These reactions involve reduction of the Nin halide to a Ni° complex in a manner similar to the generation of Wilke s bare nickel (37, 38) which can form a C8 bis-77-alkyl nickel (17) in the presence of butadiene [Eq. (9)]. It is reasonable to assume that in the presence of excess alkyaluminum chloride, an exchange reaction [Eq. (10)] can take place between the Cl" on the aluminum and one of the chelating 7r-allyls to form a mono-77-allylic species 18. Complex 18 is functionally the same as 16 under the catalytic reaction condition and should be able to undergo additional reaction with a coordinated ethylene to begin a catalytic cycle similar to Scheme 4 of the Rh system. The result is the formation of a 1,4-diene derivative similar to 13 and the generation of a nickel hydride which then interacts with a butadiene to form the ever-important 7r-crotyl complex [Eq. (11)]. 

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

On the other hand, the very nature of the co-catalytic function implies that at least a part of the co-catalyst molecule is consumed in the course of the reaction. In other words, of the ions formed by interaction of catalyst and co-catalyst, the cation must, and the anion may be incorporated in the polymer, e.g., whenever an acid is the co-catalyst, the proton is transferred during the initiation reaction to a monomer molecule which then forms the first link in the chain. The anion may or may not become attached to the end of a polymer molecule in a termination reaction. Similarly, when an alkyl halide acts as co-catalyst [6, 11], the alkyl cation necessarily forms the start of a chain, and a halide ion may be incorporated in a termination reaction. 

Ohtomi et al. (1976) have studied the catalytic effect of polypode ligands, such as [ 116] on the reactions of alkyl halides under liquid-liquid phase-transfer conditions (Table 34). Primary alkyl iodides are seen to be more reactive than the corresponding bromides. In contrast, the reactivity towards CN- declines in the order RBr > RI > RC1. It is interesting to note that this order differs from that observed in solid-liquid two-phase systems catalysed by crown ethers (Cook et al., 1974). 

Probably the most important group of phase transfer reactions, and certainly the commonest, are those in which an anion is transferred from the aqueous phase into the organic solvent, where nucleophilic substitution occurs. These would once have been performed in a dipolar aprotic solvent such as DMF. A good example is the reaction between an alkyl halide (such as 1-chlorooctane), and aqueous sodium cyanide, shown in Scheme 5.5. Without PTC, the biphasic mixture can be stirred and heated together for 2 weeks and the only observable reaction will be hydrolysis of the cyanide group. Addition of a catalytic amount of a quaternary onium salt, or a crown ether, however, will lead to the quantitative conversion to the nitrile within 2 h. 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

As has been mentioned previously, one is most likely to find analogies to catalytic reactions on solids with acidic and/or basic sites in noncatalytic homogeneous reactions, and therefore the application of established LFERs is safest in this field. Also the interpretation of slopes is without great difficulty and more fruitful than with other types of catalysts. The structure effects on rate have been measured most frequently on elimination reactions, that is, on dehydration of alcohols, dehydrohalogenation of alkyl halides, deamination of amines, cracking of the C—C bond, etc. Less attention has been paid to substitution, addition, and other reactions. 

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