Alkylation, quantitative studies

Some observations about the nitration of some polymethylbenzenes have already been made ( 6.3, 6.4). Replacement of an alkyl group has frequently been observed, but quantitative studies are laeking. 

A -(l-Haloalkyl)pyridinium halides have been advantageously employed in the Hantzsch multicomponent synthesis, yielding alkyl 1,4-dihydropyri-dine-3,5-dicarboxylates, which are a well-known class of calcium channel modulators (81AGE762). Tire halides readily interact with an excess of an ethyl 3-aminobut-2-enoate 82 (R = H) in dichloromethane at room temperature to afford the heterocycles 83 (R = H) in good to excellent yields (65-95%) (92T1263). Tliis observation has been exploited to perform a quantitative study of the reactivity of the salts (93CB1251).Tlie results have... 

Steric constraints dictate that reactions of organohalides catalysed by square planar nickel complexes cannot involve a cw-dialkyl or diaryl Ni(iii) intermediate. The mechanistic aspects of these reactions have been studied using a macrocyclic tetraaza-ligand [209] while quantitative studies on primary alkyl halides used Ni(n)(salen) as catalyst source [210]. One-electron reduction affords Ni(l)(salen) which is involved in the catalytic cycle. Nickel(l) interacts with alkyl halides by an outer sphere single electron transfer process to give alkyl radicals and Ni(ii). The radicals take part in bimolecular reactions of dimerization and disproportionation, react with added species or react with Ni(t) to form the alkylnickel(n)(salen). Alkanes are also fonned by protolysis of the alkylNi(ii). 

Most of the spectroscopic investigations discussed above were carried out on well-defined metallocene systems, either isolated species or those generated from a well-defined metallocene alkyl precursor activated with one equivalent of a borane or borate activator. Most practical polymerisation catalysts, on the other hand, include a scavenger, usually an aluminum alkyl, and may contain ill-defined activators such as methylaluminoxane (MAO), usually at high MAO/Zr ratios. Such systems are less amenable to quantitative studies nevertheless, the identifications of species such as those depicted in Schemes 8.5-8.8 has enabled similar compounds to be identified in more complex mixtures. An idea of the possible mode of action... 

A more quantitative study of the methylation or butylation of alkenyl sulfoxides with alkyl iodides was also reported31 32 (Table3). 

This scheme requires the assumption of extremely strong association of all lithium-oiganics down to at least 10-4 molar concentration if the observed reaction orders are to be obeyed. It assumes in agreement with earlier workers that only unassociated lithium alkyls and aryls are reactive. The six-fold association of butyllithium required is in agreement with physical measurements although admittedly these were carried out at much higher concentrations. Morton and co-workers (69) have shown that the polymer molecules are indeed associated into dimers in this system from a quantitative study of the decrease in solution viscosity on removal of the charged species at the ends of the polymer molecules. 

Quantitative studies have been reported for the distribution of pairs of different alkyl groups between aluminum and boron, defined by the constant of Eq. (97) where al = 1 /3 A1 and b = 1/3 B. 

The application of the ideas of Lewis on acids, which correlate a wide range of phenomena in qualitative fashion, has as yet led to very few quantitative studies of reaction velocity but has led to detailed speculations as to mechanisms (Luder and Zuffanti, 118). Friedel-Crafts reactions are considered to be acid-catalyzed, the formation of a car-bonium ion being the first step. The carbonium ion then acts as an acid relative to the base benzene which, upon loss of a proton, yields the alkylated product. Isomerizations of isoparaffins can be explained in similar fashion (Schneider and Kennedy, 119). An alkyl halide yields a carbonium ion on reaction with acids such as boron trifluoride, aluminum chloride, and other metal halides. 

However, where quantitative studies have been made on tumours with acquired resistance to a particular alkylating agent, it is a general finding that such tumours are then cross resistant to all other difunctional agents36> 72 >. There must therefore be some basic mechanism of resistance which can work... 

The high reactivity of chelated lithium alkyl compounds severely limits structural study of pure compounds, particularly in aromatic solvents. Most of our more recent work on chelated lithium alkyl systems used H and 7Li NMR to observe various metalation reactions like the self-metalation or aging reaction of TMED LiBu in heptane (I, 2). Much of our current insight into the structural features of chelated alkali metal systems comes from careful quantitative study of systems with relatively stable anions like resonance stabilized carbanions (5) and the systems described in this paper. We discuss magnetic resonance experiments on two systems (a) chelated lithium halides Chel LiX, examples of the recently discovered inorganic salt chelates (6), and (b)... 

As would be expected, deuterium exchange between nitromethane and D2O is catalyzed by acetate ions, and the rate of exchange is equal to the rate of bromination under the same conditions (Reitz, 43). Similar correspondences would be expected in the rate of racemization of optically active nitro compounds, but here the position has been complicated by reports (Kuhn and Albrecht, 45 Shriner and Young, 46) that these compounds do not lose their activity completely on conversion to the ion. However, it has recently been shown (Kornblum et al., 47, 48) that the residual activity in these observations was due to the presence of alkyl nitrate as an impurity. The mutarotation of a-nitro camphor represents a similar type of reaction it is catalyzed both by acids and bases (Lowry, 49), and a quantitative study of acid catalysis in chlorobenzene solution has been made (Bell and Sherred, 50). Lowry and most subsequent writers have supposed that the observed change of rotation is due to conversion to the aci-nitro form (II), i.e.,... 

An interesting observation was reported by Deady who advocated a lone-pair cooperativity in the N-alkylation of some N,N -bridged 2,2 -bii-midazoles. The second order rate constants of alkylation are in the order 525 > 524 > 523. Bridging has a considerable effect on the reactivity of the nitrogen atom (81AJC2569). Such a quantitative study would be interesting on other ortho-orthc/-Mnked azaheterocycles. 

Alkyl cations are not as amenable to quantitative study as the stable carbonium ions just described. Some success has been achieved in extending the method of measuring equilibria by utilizing UV spectroscopic detection of the carbonium ion to substituted allyl cations generated by protonation of dienes. For a representative case, the equilibrium... 

A quantitative study of the reaction of a d square planar Pt(II) by a free-radical chain mechanism was reported by HUl and Puddephatt and is summarized in Scheme 7.6. The radical chain was initiated by photochemical MLCT (metal-to-ligand charge transfer) to form [Me2Pt+(phen)"], which has primarily triplet character. This intermediate then abstracts an iodine atom to generate an alkyl radical. Consistent with the more common occurrence of radical mechanisms with alkyl iodides than bromides, the reaction of isopropyl bromide was unaffected by light, by benzoquinone that would scavenge R , or by the presence or absence of oxygen. ... 

AT-chlorosuccinimide in MeOH (PhSCHRBRj - PhSCHROMe)/ methanolysis of 5-monomethyl dithioacetal fluorosulphonates, and addition of an alkyl-lithium to thiono-esters. Quantitative studies have been reported for an interesting variation on the simplest preparation, in which hemithioacetals exist in equilibrium with an aldehyde and a mixture of two thiols. ... 

Zahorszky (1982) has made extensive quantitative studies on the competitive loss of alkyl radicals from M . The abundance ratio of the resulting product... 

Wu, B. Q., Zeng, F. W, Ge, M., Cheng, X., and Wu, G., A new synthetic route to a-aryl propionic acid and a quantitative study of the photo-Sr I reaction of aryl halides with carbanion from alkyl nitrile, Sci. China, 34, 111, 1991. 

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