Alkylation reactions compounds

Unsubstituted secondary phosphine 2 was obtained by the reaction of the dichloride 101 with phosphine PH3 in a toluene/dimethyl sulfoxide (DMSO)/water mixture (75% yield). The reactivity of the PH function of 2 and its BH3 adduct 3 was examined in deprotonation and alkylation reactions. Compounds 2 and 3 were shown to readily react with diphenyl(vinyl)phosphine and 2-vinylpyridine to give 4 and 5, respectively. Compound 5 was converted into free trisubstituted phosphine 6 upon treatment with diethylamine <1998IC6408>. 

A variety of C2-symmetric diphenyl-phosphoramides, -thiophosphoramides and -selenophosphoramides have been used as chiral catalysts in alkylation reactions. ° " ° Compounds (350) and (351) ° and the selenophosphoramidates (352), (353), and (354) " act as ligands in Ti(IV)-catalysed asymmetric addition reactions of diethylzinc to aldehydes to give secondary alcohols with e.e. values of 40 to 83%. The diphenylthiophosphoramidates(351), (355), and (356) similarly act as ligands in Ag(I)-promoted enatioselective allylation of aldehydes with... 

The Alkyl Halides. Ethyl bromide and iodide (see below) are typical alkyl halides. Compounds of this class are of very great importance in synthetic work, owing to the reactivity of the halogen atom. This is illustrated by the following reactions ... 

The acidic properties of sulphonamides and their mono-substitution derivatives are particularly well illustrated in the alkyl ubstitution compounds, which by reason of these properties can be prepared by two distinct methods. Thus mono- and di-ethylamine, when subjected to the Schotten-Baumann reaction using benzenesulphonyl chloride, gi e benzenesulphonethylamide, and bcnzenesulphondiethylamide respectively. These compounds can also... 

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

The transmetallation of various organometallic compounds (Hg, Tl, Sn, B, Si, etc.) with Pd(II) generates the reactive cr-aryl, alkenyl, and alkyl Pd compounds. These carbopalladation products can be used without isolation for further reactions. Pd(II) and Hg(II) salts have similar reactivity toward alkenes and aromatic compounds, but Hg(II) salts form stable mercuration products with alkenes and aromatic rings. The mercuration products are isolated and handled easily. On the other hand, the corresponding palladation products are too reactive to be isolated. The stable mercuration products can be used for various reactions based on facile transmetallation with Pd(II) salts to generate the very reactive palladation products 399 and 400 in rim[364,365]. 

Kharasch called this the peroxide effect and demonstrated that it could occur even if peroxides were not deliberately added to the reaction mixture Unless alkenes are pro tected from atmospheric oxygen they become contaminated with small amounts of alkyl hydroperoxides compounds of the type ROOH These alkyl hydroperoxides act m the same way as deliberately added peroxides promoting addition m the direction opposite to that predicted by Markovmkov s rule... 

Vinylboranes are interesting dienophiles in the Diels-Alder reaction. Alkenylboronic esters show moderate reactivity and give mixtures of exo and endo adducts with cyclopentadiene and 1,3-cyclohexadiene (441). Dichloroalkenylboranes are more reactive and dialkylalkenylboranes react even at room temperature (442—444). Dialkylalkenylboranes are omniphilic dienophiles insensitive to diene substitution (444). In situ formation of vinyl-boranes by transmetaHation of bromodialkylboranes with vinyl tri alkyl tin compounds makes possible a one-pot reaction, avoiding isolation of the intermediate vinylboranes (443). Other cycloadditions of alkenyl- and alkynylboranes are known (445). 

Organochromium Catalysts. Several commercially important catalysts utilize organ ochromium compounds. Some of them are prepared by supporting bis(triphenylsilyl)chromate on siUca or siUca-alumina in a hydrocarbon slurry followed by a treatment with alkyl aluminum compounds (41). Other catalysts are based on bis(cyclopentadienyl)chromium deposited on siUca (42). The reactions between the hydroxyl groups in siUca and the chromium compounds leave various chromium species chemically linked to the siUca surface. The productivity of supported organochromium catalysts is also high, around 8—10 kg PE/g catalyst (800—1000 kg PE/g Cr). 

Dicyclopentadiene is also polymerized with tungsten-based catalysts. Because the polymerization reaction produces heavily cross-Unked resins, the polymers are manufactured in a reaction injection mol ding (RIM) process, in which all catalyst components and resin modifiers are slurried in two batches of the monomer. The first batch contains the catalyst (a mixture of WCl and WOCl, nonylphenol, acetylacetone, additives, and fillers the second batch contains the co-catalyst (a combination of an alkyl aluminum compound and a Lewis base such as ether), antioxidants, and elastomeric fillers (qv) for better moldabihty (50). Mixing two Uquids in a mold results in a rapid polymerization reaction. Its rate is controlled by the ratio between the co-catalyst and the Lewis base. Depending on the catalyst composition, solidification time of the reaction mixture can vary from two seconds to an hour. Similar catalyst systems are used for polymerization of norbomene and for norbomene copolymerization with ethyhdenenorbomene. 

This reaction gives fair-to-good yields of monoorganotin tribromides and trichlorides when quaternary ammonium or phosphonium catalysts are used (149). Better yields are obtained with organic bromides and staimous bromide than with the chlorides. This reaction is also catalyzed by tri alkyl antimony compounds at 100—160°C, bromides are more reactive than chlorides in this preparation (150,151). a,C0-Dihaloalkanes also react in good yield giving CO-haloalkyltin trihaHdes when catalyzed by organoantimony compounds (152). 

Side-chain anionic alkylation reactions with aromatic compounds take place when cataly2ed with strong basic catalysts, like Na—K (228). The yield is 83% when o-xylene reacts with butadiene... 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

The reaction of alkyl nitro compounds with acetyl chloride in the presence of an alkenic compound produced a 2-isoxazoline. The mechanism is believed to proceed via a nitrile oxide and is illustrated in Scheme 112 (B-79MI41613). 

The generation of caibocations from these sources is well documented (see Section 5.4). The reaction of aromatics with alkenes in the presence of Lewis acid catalysts is the basis for the industrial production of many alkylated aromatic compounds. Styrene, for example, is prepared by dehydrogenation of ethylbenzene made from benzene and ethylene. 

The unique feature of the SrnI reactions of substituted alkyl nitro compounds is the facility with which carbon-carbon bonds between highly branched centers can be formed. This point is illustrated by several of the examples in Scheme 12.7. 

Meyers has demonstrated that chiral oxazolines derived from valine or rert-leucine are also effective auxiliaries for asymmetric additions to naphthalene. These chiral oxazolines (39 and 40) are more readily available than the methoxymethyl substituted compounds (3) described above but provide comparable yields and stereoselectivities in the tandem alkylation reactions. For example, addition of -butyllithium to naphthyl oxazoline 39 followed by treatment of the resulting anion with iodomethane afforded 41 in 99% yield as a 99 1 mixture of diastereomers. The identical transformation of valine derived substrate 40 led to a 97% yield of 42 with 94% de. As described above, sequential treatment of the oxazoline products 41 and 42 with MeOTf, NaBKi and aqueous oxalic acid afforded aldehydes 43 in > 98% ee and 90% ee, respectively. These experiments demonstrate that a chelating (methoxymethyl) group is not necessary for reactions to proceed with high asymmetric induction. 

The formation of quaternary salts by attack at an oxygen atom is only achievable in certain special cases. Most of the attempts to effect reactions of this type with N-alkyl-a-oxo derivatives have failed. Until recently it might have been assumed that 2-alkoxy-quaternary salts were unobtainable, the usual product from reactions with the alkoxy derivatives being the N-alkyl-oxo compounds (see Section IV,C). Recently, however, Meerwein and his co-workers found that triethyloxonium borofluoride and a number of N-methyl-a-oxo... 

Reactions of iV -alkylated or arylated azinium compounds with nucleophiles proceed more readily than those of the parent, uncation-ized azines, and the ring tends to open. The iV -substituent may bring into play an accelerative effect from the London forces of attraction. Increased displaceability of the substituent in iV -alkyl-azinium compounds has been noted for 2-halopyridinium (87) 1-haloisoquinolinium, 4-halopyrimidinium, 4-methoxypyrid-inium (88), 4-phenoxy- and 4-acetamido-quinazolinium (89), 3-methylthiopyridazinium, and 2-car boxymethylthiopyrimidi-nium salts (90). The latter was prepared in situ from the iV -alkyl-pyrimidine-2-thione. The activation can be effectively transmitted to... 

Drawbacks as known from the Friedel-Crafts alkylation are not found for the Friedel-Crafts acylation. In some cases a decarbonylation may be observed as a side-reaction, e.g. if loss of CO from the acylium ion will lead to a stable carbenium species 8. The reaction product of the attempted acylation will then be rather an alkylated aromatic compound 9 ... 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

Substitution of a 2-pyridyl residue for the phenyl attached rectly to nitrogen affords a series of potent antihistamines, eparation of these compounds, too, is accomplished by a series alkylation reactions. It is further probable that the order the reaction can be readily interchanged. Thus, alkylation 2-aminopyridine with the chloroethyldimethylamine side chain ads to the diamine, 59. Alkylation with benzyl chloride af-rds tripelenamine (60) reaction with p-methoxybenzyl chloride ads to pyrilamine (61), °... 

Of the several syntheses available for the phenothiazine ring system, perhaps the simplest is the sulfuration reaction. This consists of treating the corresponding diphenylamine with a mixture of sulfur and iodine to afford directly the desired heterocycle. Since the proton on the nitrogen of the resultant molecule is but weakly acidic, strong bases are required to form the corresponding anion in order to carry out subsequent alkylation reactions. In practice such diverse bases as ethylmagnesium bromide, sodium amide, and sodium hydride have all been used. Alkylation with (chloroethyl)diethylamine affords diethazine (1), a compound that exhibits both antihista-minic and antiParkinsonian activity. Substitution of w-(2-chloroethyl)pyrrolidine in this sequence leads to pyrathiazine (2), an antihistamine of moderate potency. 

The Friedel-Crafts allcylation reaction usually involves the interaction of an allcy-lation agent such as an alkyl halide, alcohol, or alkene with an aromatic compound, to form an alkylated aromatic compound (Scheme 5.1-44). 

Keim and co-workers have carried out various alkylation reactions of aromatic compounds in ionic liquids substantially free of Lewis acidity [84]. An example is the reaction between benzene and decene in [BMIM][HS04], which was used together with sulfuric acid as the catalyst (Scheme 5.1-54). These authors have also claimed that these acid-ionic liquids systems can be used for esterification reactions. 

A. Alkylation Reaction of Toluene as Model Compound with Epichlorohydrin... 

The mechanism of chemical modification reactions of PS were determined using toluene as a model compound with EC in the presence of BF3-0(C2H5)2 catalyst and the kinetics and mechanism of the alkylation reaction were also determined under similar conditions [53-55]. The alkylation reaction of toluene, with epichlorohydrin, underwent polymerization of EC in the presence of Lewis acid catalysis at a low temperature (273 K) as depicted in Scheme (9). 

The Sn2 alkylation reaction between an enolate ion and an alkyl halide is a powerful method for making C-C bonds, thereby building up larger molecules from smaller precursors. We ll study the alkylation of many kinds of carbonyl compounds in Chapter 22. 

How might you prepare the following compounds using an alkylation reaction as the key step ... 

There is no simple answer to this question, but the exact experimental conditions usually have much to do with the result. Alpha-substitution reactions require a full equivalent of strong base and are normally carried out so that the carbonyl compound is rapidly and completely converted into its enolate ion at a low temperature. An electrophile is then added rapidly to ensure that the reactive enolate ion is quenched quickly. In a ketone alkylation reaction, for instance, we might use 1 equivalent of lithium diisopropylamide (LDA) in lelrahydrofuran solution at -78 °C. Rapid and complete generation of the ketone enolate ion would occur, and no unreacled ketone would be left so that no condensation reaction could take place. We would then immediately add an alkyl halide to complete the alkylation reaction. 

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