Maleic anhydride nucleophilic attack

Mendez, F., and M. Galvan. 1991. Nucleophilic Attacks on Maleic Anhydride A Density Functional Approach. Density Functional Methods in Chemistry, J. K. Labanowski and J. Andzelm, eds. New York, Springer-Verlag, 387-400. 

The photocycloaddition of aliphatic ketones to the electron-deficient double bonds of frans-l,2-dicyanoethylene282,283 and maleic anhydride 282 [Eq. (72)] is believed to proceed by an alternative mechanism involving nucleophilic attack on the double bond by the n, ir singlet state of the carbonyl,... 

The kinetics of the reactions of phthalic and maleic anhydrides with Z-substituted phenols (Z = H, m-Me, p-Me, m-Cl, p-C 1, and -CN) (Scheme 8) were studied in aqueous solution at pH 8.5. Two kinetic processes well separated in time were observed. The fast process was attributed to the formation of the aryl ester in equilibrium with the anhydride and allowed the determination of the rate of nucleophilic attack of the phenol on the anhydride. From the slow kinetic process, the equilibrium constant for this reaction was determined. The Brpnsted-type plots for the nucleophilic attack of substituted phenols on the anhydrides were linear with slopes /SNuc of 0.45 and 0.56 for phthalic and maleic anhydride, respectively. The results are consistent with a mechanism involving rate-determining nucleophilic attack and also with a concerted mechanism.27... 

Deacylation of derivatives formed by acid anhydrides (maleic, citra-conic, and 2,3-dimethylmaleic) containing double bonds (cis) occurs at a much faster rate under mild conditions. Several mechanisms have been proposed for deacylating these derivatives formed from the double bond containing anhydrides (9,46,47,48,49). The most important structural factor in the deacylation process is the cis double bond which maintains the terminal carboxyl group in the spatial orientation that makes a nucleophilic attack on the amide carbon much more probable. 

The chemistry of these very electron-deficient rings mostly concerns nucleophilic attack and displacement of leaving groups such as Cl by nucleophiles such as alcohols and amines. To introduce this subject we need to take one heterocyclic synthesis at this point, though these are properly the subject of the next chapter. The compound maleic hydrazide has been known for some time because it is easily formed when hydrazine is acylated twice by maleic anhydride. 

The selectivities demonstrated by unsymmetrical maleic and phthalic anhydrides for attack of a nucleophile on one carbonyl group rather than on the other are large enough to demand explanation. In principle, maleic anhydride 126 can undergo attack by a nucleophile at either of the two carbonyl carbons Ca and Cp. However, there is exclusive attack at C by lithium aluminum hydride when R is a methoxy group. The ratio of attack at C versus Cp reduces only slightly to 88 12 when R is a... 

Furthermore, high regioselectivity is observed in unsaturated cyclic anhydrides, such as maleic anhydrides and phthalic anhydrides (Scheme 6.25) [166 a, b,e, 174, 175] where substitution cannot introduce steric hindrance to the nucleophile attack. Kayser and Morand concluded that in such cases the most important factor is the intrinsic reactivity of the carbonyl group, which can be modeled by ab initio calculations of the LUMO coefficients for the ground-state geometries of the anhydrides... 

The iV-propargylaminophosphines (78) readily rearrange to give the azabuta-dienylphosphine (79) via intramolecular nucleophilic attack of phosphorus at the terminal acetylenic carbon. Full details have now appeared of the reactions of 2 -1,2,3-diazaphosphole derivatives (80) with alkyl halides, giving 2,3-disub-stituted indoles as the major product. Several examples of the attack of phosphines at carbon of a, -unsaturated carbonyl compounds have been described. The betaine (81) is the active intermediate in the triphenylphosphine-induced polymerization of maleic anhydride. Phosphines also catalyse the... 

The starting material is made by a photochemical [2 + 2] cycloaddition of acetylene and maleic anhydride. Treatment with butanol and base gives the monoester because, after butanol has attacked once, the product is the anion of a carboxyhc acid and cannot be attacked again by the nucleophile. 

We are going to look at these compounds briefly here. Pyrimidine is more important than either of the others because of its involvement in DNA and RNA— you will find this in Chapter 42. All three compounds are very weak bases—hardly basic at all in fact. Pyridazine is slightly more basic than the other two because the two adjacent lone pairs repel each other and make the molecule more nucleophilic (the a effect again see p. 513). The chemistry of these very electron-deficient rings mostly concerns nucleophilic attack and displacement of leaving groups such as Cl by nucleophiles such as alcohols and amines. To introduce this subject we need to take one heterocyclic synthesis at this point, although these are properly the subject of the next chapter. The compound maleic hydrazide has been known for some time because it is easily formed when hydrazine is acylated twice by maleic anhydride. 

Two papers reporting on cycloaddition reactions of dithio-esters have appeared. Smutny and his co-workers obtained 2/f-thiopyrans (279) from the reaction of methyl 3-(dialkylamino)dithioacrylate with maleic anhydride. They interpreted the reaction in terms of an initial nucleophilic attack of the thiocarbonyl sulphur atom on the electrophilic double bond of the anhydride, forming the intermediate (280), and a subsequent... 

Theory has been used predominantly to probe the nature of the sites on vanadium clusters and model vanadium oxide surfaces. Cluster and p>eriodic DFT calculations [68,69] have been carried out in order to imderstand the electronic and structural properties of the exposed (100) surface of (VO)2P207. Both cluster and slab calculations reveal that surface vanadium sites can act as both local acid and base sites, thus enhancing the selective activation of n-butane as well as the adsorption of 1-butene. Vanadium accepts electron density from methylene carbon atoms and, thus aids in the subsequent activation of other C-H bonds. Calculations reveal that that the terminal P=0 bonds lie close to the Fermi level and thus present the most nucleophihc oxygen species present at the surface for both the stoichiometric as well as phosphate-terminated surfaces. These sites may be involved in the nucleophilic activation of subsequent CCH bonds necessary in the selective oxidative conversion of butane into maleic anhydride. Full relaxation of the surface, however, tends to lead to a contraction of the terminal P=0 bonds and a lengthening of the P V bonds. This pushes the P V states, initially centered on the oxygen atoms, higher in energy and thus increases their tendency to be involved in nucleophilic attack . 

The Diels-Alder adducts 2 and 6 retain the anhydride function that was originally present in the dienophile, maleic anhydride. As a rule, this functionality is unstable in the presence of water even at pH 7 and hydrolyzes to a dicarboxylic acid according to the general sequence outlined in Scheme 12.1. This process is initiated by nucleophilic attack of water on the carbonyl function, followed by cleavage of a C-O bond of the anhydride. Because anhydrides are reactive toward water, it is important that the apparatus and reagents you use are dry to maximize the yield of cycloadduct. You may be instructed to prepare the dicarboxylic acids 7 and 8 by intentional hydrolysis of the corresponding anhydrides. Protocols for doing so are included in Part C of the experimental procedures. 

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