Benzylic halides, alkylation oxidation

Finally, the hybridization of the carbon atom also has a marked effect on its willingness to attach to the transition metal. Allyl or benzyl halides undergo oxidative addition faster than aromatic or vinyl halides. The least reactive are alkyl halides which require the use of nickel(O)9 complexes or highly active catalyst systems.10 If we start from an optically active substrate, then the oxidative addition usually proceeds in a stereoselective manner. 

Oxidative addition [1, 38] of 1-alkenyl, i-alkynyl, allyl, benzyl, and aiyl halides to a palladium(O) complex affords a stable rra .s-<7-palladium(II) complex (11). The reaction proceeds with complete retention of configuration for alkenyl halides and with inversion for allylic and benzylic halides. Alkyl halides having /3-hydrogens are rarely useful because the oxidative addition step is very slow and may compete with /3-hydride elimination from the a-organopalladium(II) species. However, it has been recently shown that iodoalkanes undergo the cross-coupling reaction with organoboron compounds (Section 2.4.5). 

Acidic conditions for hydroxy deiaotection can be avoided if benzyl-type ethers are used as the blocking functions. Hiey can be prepared fiom the alcohols by alkylation with benzyl halide/sodium hydride in DMSO or benzyl halide/silveifl) oxide in DMF (the silver salt does not cause acyl migration as a side... 

Experimental tests of the theoretical predictions have involved the electrochemical reduction of alkyl and benzyl halides as well as their reduction by homogeneous electron donors.22,29-31 In the first case, AG° = E - rx r.+x=f where E is the electrode potential and rx r.+x=f is the standard potential of the RX/R + XT couple. In the homogeneous case, AG° = E q — rx r-+xt> where E Q is the standard potential of the outer-sphere electron donor or acceptor couple P/Q, and + stands for a reduction and — for an oxidation. 

The possibility that substitution results from halogen-atom transfer to the nucleophile, thus generating an alkyl radical that could then couple with its reduced or oxidized form, has been mentioned earlier in the reaction of iron(i) and iron(o) porphyrins with aliphatic halides. This mechanism has been extensively investigated in two cases, namely the oxidative addition of various aliphatic and benzylic halides to cobalt(n) and chromiumfn) complexes. 

Compositions and functions of typical commercial products in the 2-alkyl-l-(2-hydroxyethyl)-2-imidazolines series are given in Table 29. 2-Alkyl-l-(2-hydroxyethyl)-2-imidazolines are used in hydrocarbon and aqueous systems as antistatic agents, corrosion inhibitors, detergents, emulsifiers, softeners, and viscosity builders. They are prepared by heating the salt of a carboxylic acid with (2-hydroxyethyl)ethylenediamine at 150—160°C to form a substituted amide 1 mol water is eliminated to form the substituted imidazoline with further heating at 180—200°C. Substituted imidazolines yield three series of cationic surfactants by ethoxylation to form more hydrophilic products quatemization with benzyl chloride, dimethyl sulfate, and other alkyl halides and oxidation with hydrogen peroxide to amine oxides. 

Another way to oxidize primary alkyl halides to aldehydes is by the use of hexamethylenetetramine followed by water. However, this reaction, called the Sommelet reaction. is limited to benzylic halides. The reaction is seldom useful when the R in RCH2CI is alkyl. The first part of the reaction is conversion to the amine ArCH2NH2 (0-44), which can be isolated. Reaction of the amine with excess hexamethylenetetramine gives the aldehyde. It is this last step that is the actual Sommelet reaction, though the entire process can be conducted without isolation of intermediates. Once the amine is formed, it is converted to an imine (ArCH2N=CH2) with formaldehyde liberated from the reagent. The key step then follows transfer of hydrogen from another mole of the arylamine to the imine ... 

The addition of an alkyl halide to the d7 complex [Co(CN)6]3- results in a one-electron oxidation of the metal and proceeds by homolytic abstraction of halogen. For a methyl or benzyl halide, an organocobalt product is formed,... 

Alkyl halides that do not readily undergo nucleophilic attack may oxidatively add to a metal by radical mechanisms. Oxidative addition reactions that occur by radical mechanisms show loss of stereochemistry, nomeproducible rates, inhibition by radical inhibitors, and acceleration by O2 or light. Reactions of lr(Cl)(CO)(PMe3)2 with methyl and benzyl halides showed no indication of radical behavior, but other saturated alkyl halides, vinyl, and aryl halides showed characteristics consistent with a radical-chain pathway. 

Hydrogenolysis of 4-benzylpiperazine-2,6-diones over palladium-charcoal produced 4-unsubstituted piperazine-2,6-diones in high yield. The amino group in l-phenylpiperazine-2,6-dione underwent alkylation with benzyl chloride and phenacyl bromide, but not with simple alkyl halides (1638). Oxidative dimerizations of piperazine-2,6-diones in nitrobenzene have been studied (1639). 2,6-Bis(hydroxy-imino)piperazine heated with palladium-charcoal in o-dichlorobenzene gave 2,6-diaminopyrazine (465). 

A communication and full paper tell of the efficient photoreduction of 4-chlorobiphenyl to biphenyl by excitation of 9,10-dihydro-lO-methylacridine (163) or acriflavine (164) in aqueous acetonitrile containing sodium borohydride. A variety of alkyl halides, benzyl halides and chlorobenzenes were also reduced. The reaction proceeds by electron transfer from the excited state of the dihydroacridine to the chloroarene, chloride loss and hydrogen atom donation to the arene radical. Thus photoreduction of the arene is coupled with oxidation of the dihydroacridine to the acridinium salt the latter is reduced back to the dihydroacridine by the borohydride. 

When RX is easily reduced, as in the case of allyl iodides and benzyl bromides, the competing further reduction of the intermediate radical is suppressed and radical reactions such as dimerization, addition to double bonds and aromatic compounds or reaction with anions can be favored. The radical pathway can be also promoted by catalysis with reduced forms of vitamin Bn, cobaloximes or nickel complexes. These react with the alkyl halide by oxidative addition and release the alkyl radical by homolytic cleavage. 

The reactivities of alkyl halides are in the sequence RI > RBr > RCl and MeX > EtX > PrX. Benzyl halide reactions with tin do not require catalysts (equation 2). For less reactive halides, the catalysts and promoters employed include metals (sodium, magnesium, zinc, or copper), Lewis bases (amines, triorganophosphines and -stibines, alcohols, or ethers), iodides, and onium salts (R4MX). The use of tin-sodium alloys can result in tri- or tetraorganotin products. Electrochemical synthesis has also been reported, e.g. the formation of R2SnX2 from the oxidation of anodic tin by RX in benzene solution and the formation of R4Sn from RI (R = Me or NCCH2CH2) and cathodic tin. 

Pyridine-A -oxides undergo alkylation and acylation at oxygen. O-Alkylation occurs most readily with benzyl halides under mild conditions and leads to 1-benzyloxypyridinium ions, e.g. 84,... 

Cuprous chloride tends to form water-soluble complexes with lower olefins and acts as an IPTC catalyst, e.g., in the two-phase hydrolysis of alkyl chlorides to alcohols with sodium carboxylate solution [10,151] and in the Prins reactions between 1-alkenes and aqueous formaldehyde in the presence of HCl to form 1,3-glycols [10]. Similarly, water-soluble rhodium-based catalysts (4-diphenylphosphinobenzoic acid and tri-Cs-io-alkylmethylam-monium chlorides) were used as IPTC catalysts for the hydroformylation of hexene, dodecene, and hexadecene to produce aldehydes for the fine chemicals market [152]. Palladium diphenyl(potassium sulfonatobenzyl)phosphine and its oxide complexes catalyzed the IPTC dehalogenation reactions of allyl and benzyl halides [153]. Allylic substrates such as cinnamyl ethyl carbonate and nucleophiles such as ethyl acetoactate and acetyl acetone catalyzed by a water-soluble bis(dibenzylideneacetone)palladium or palladium complex of sulfonated triphenylphosphine gave regio- and stereo-specific alkylation products in quantitative yields [154]. Ito et al. used a self-assembled nanocage as an IPTC catalyst for the Wacker oxidation of styrene catalyzed by (en)Pd(N03) [155]. 

The alkylpalladium(IV) complexes obtained by oxidative addition of alkyl (methyl, allyl, and benzyl) halides to the palladium(ll) metallacycle spontaneously undergo reductive elimination. This implies migration of the alkyl group R onto the aromatic site of the palladacycle (Eq. 19, R=CH2Ph, 72% yield). 

In the presence of a Lewis acid, silyl enol ethers can be alkylated with reactive secondary halides, such as substituted benzyl halides, and with chloromethylphenyl sulfide (ClCH2SPh), an activated primary halide. Thus, reaction of the benzyl chloride 10 in the presence of zinc bromide with the trimethylsilyl enol ether derived from mesityl oxide allowed a short and efficient route to the sesquiterpene ( )-ar-turmerone (1.22). Reaction of ClCH2SPh with the trimethylsilyl enol ethers of lactones in the presence of zinc bromide, followed by 5-oxidation and pyrolytic ehmination of the resulting sulfoxide (see Section 2.2), provides a good route to the a-methylene lactone unit common in many cytotoxic sesquiterpenes (1.23). Desulfurization with Raney nickel, instead of oxidation and elimination, affords the a-methyl (or a-alkyl starting with RCH(Cl)SPh) derivatives. ... 

Related to these reactions is the oxidation of alkyl halides or tosylates to carbonyl compounds with dimethyl sulfoxide (or trimethylammonium A/-oxide). The reaction is effected simply by warming the halide (normally the iodide) or sulfonate in DMSO (or MeaNO), generally in the presence of a proton acceptor such as sodium hydrogen carbonate or a tertiary amine. Oxidation never proceeds beyond the carbonyl stage and other functional groups are unaffected. The reaction has been applied to benzyl halides, phenacyl halides, primary sulfonates and iodides and a limited number of secondary sulfonates. With substrates containing a secondary rather than primary halide or sulfonate elimination becomes an important side reaction and the oxidation is less useful with such compounds. 

Selective C2-alkylation of pyridine N-oxides was successfully developed by Mai (26 —> 31) (2012SL938) (benzyl halides, Scheme 14a) and Fu (26 32) (2013JA616) (secondary and tertiary alkyl bromides (Scheme... 

Simple optically active phosphines can be converted back into phosphonium salts without any change of configuration if benzyl or alkyl halides are used (reversal of Equation 13.57). Oxidation to phosphine oxides with hydrogen peroxide or sulphurisation to phosphine sulphides with elemental sulphur also proceeds with retention of configuration. On the other hand, racemisation or complete inversion occurs if oxidation is carried out with diethyl peroxide. Halogenation to a phosphonium compound followed by hydrolysis results in inversion (13.63). 

Oxidative addition of simple alkyl halides (Mel, benzyl halides, etc.) to [IrCl(CO)(PPhg)2] are second order, but aryl iodides react very much more slowly (moderate rates only at about 150°C) and by a two-term rate law -d[Ir ]/d/==(A i-t-A 2[Arl])[Iri] with / 2 = 7[PPh3]. The mechanism illustrated in equations (11)—(13) is consistent with the rate law if jSTx pPPhg] (L=triaryl-phosphine, S=solvent) ... 

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