Dialkyl succinates

An important use of dialkyl succinates is in the preparation of dialkyl succinyl succinates (35,53—56), which are intermediates in the manufacture of quinacridone pigments. The reaction is carried out in the presence of alkaU metal alkoxides (eq. 2). 

Condensation with Aldehydes and Ketones. Succinic anhydride and succinic esters in the presence of different catalysts react in the gas phase with formaldehyde to give citraconic acid or anhydride and itaconic acid (94—96). Dialkyl acyl succinates are obtained by reaction of dialkyl succinates with C 4 aldehydes over peroxide catalysts (97). 

The symmetrical dialkyl succinic acids exist in tw o forms, each yielding a separate anhydride. From their similaritv to... 

Silyi enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in DMSO or certain other polar aprotic solvents." The reaction has been performed with R , R = hydrogen or alkyl, though best yields are obtained when r = r = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyi enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-Bp3-Et20," ceric ammonium nitrate," and lead tetraacetate." If R =0R (in which case the substrate is a ketene silyi acetal), dimerization with TiCU leads to a dialkyl succinate (34, r =0R)." ... 

Table 4.6 shows some experimental data on a-a dialkyl succinic acids. The most remarkable finding is that some of these molecules have a very large negative cooperativity, far beyond what could be explained by electrostatic theories. These molecules exist in two isomers—the meso and racemic forms. The latter exists in two optically active enantiomers that are mirror images of each other—only one of these is shown in Fig. 4.29. 

The model used for the a-a dialkyl succinic acid is essentially an extension of the model used in the previous subsection. Here, instead of the two hydrogens on the C -carbones we have one alkyl group R on each of the C carbones, as shown in Fig. 4.30. 

Figure 4.30. Molecular model for dialkyl succinic acid. The C -C distance is 1.54 A the C-C-C angles are tetrahedral, Qj- = 109.47 °. The center of the negative charge was placed at a distance of 1.25/2 = 0.625 A from Ae carboxyl carbon atom, and the positive charge at a distance of 0.7 A from the negative charge. The effective radii for the various alkyl groups were computed from the van der Waals volumes given by Bondi (1968). These are methyl, 1.75 A ethyl, 1.78 A isopropyl, 2.0 A tert-butyl, 2.2 A. These radii were used to construct the Lennard-Jones potentials between the various groups [see Eq. (4.8.46)].

Xq, Df and Dj are fixed, we proceed to compute the relevant quantities for the dialkylated succinic acid. 

In the case of dialkylated succinic acid, we have seen that, due to the occurrence of two barriers in the rotational potential of the racemic form (and not of the meso form) with the bulkier alkyl groups (and not the smaller ones), it is likely that the system will freeze-in into a mixture of two components. This is exactly where we observed very large negative cooperativity in the experimental data shown in Table 4.6. One cannot avoid the conclusion that at least a substantial part of the observed cooperativity is spurious. 

Vinylic and aryl halides can be used to vinylate or arylate carboxylic esters (but not ketones) by the use of NiBr2 as a catalyst.1463 However, ketones have been vinylated by treating their enol acetates with vinylic bromides in the presence of a Pd compound catalyst.1464 Also as in 0-94, this reaction can be used to close rings.1465 In one example of this, rings have been closed by treating a diion of a dialkyl succinate with a l,cu-dihalide or ditosylate,1466, e.g. ... 

The oxycarbonylation of propene under the same conditions results in the formation of crotonic acid as the major product instead of the more valuable methacrylic acid.439 When the oxycarbonylation of ethylene or terminal alkenes is carried out in anhydrous alcoholic solvents instead of acetic acid, dialkyl succinates and /3-alkoxy esters are the major products (equation 173).441,442... 

Lippert and Reid reported that heating a methanolic solution of dialkyl succinate and ethylenediamine (ED) produced bislactam 18 (39USP2156300). The same compound was prepared more recently using sodium isoprop-oxide as a catalyst. The isomeric 1,4-diazocine 65 was prepared by condensing oxalyl chloride with tetramethylenediamine (68MI1). 

Summarizing the different results from the literature, under the conditions of oxidative carbonylation in the presence of alcohols and catalytic amounts of PdCl2, esters of a,)0-unsaturated carboxylic acids, j0-alkoxy-esters and 2-sub-stituted dialkyl succinates are generally obtained, or mixtures of all of these compounds. Preferably CuCl2, but also other transition metal salts, can be used as co-catalysts (eq. (2)). 

The reaction of ethylene with CO and oxygen using alcohols as solvents and PdCl2/FeCl3 as the catalyst system may serve as another well-developed example. Dialkyl succinates are obtained in fair yields, while alkyl )9-alkoxypropionates occur as side products [6, 68]. Simultaneously generated water is removed by the addition of orthoformates to the reaction mixture, supressing the undesirable formation of carbon dioxide. Increased yields are found if the concentration of chloride ions is reduced by adding sodium acetate as a buffer. 

Stobbe condensation Formation of alkylidene succinic acids or their monoesters from dialkyl succinates and carbonyl compounds. 442... 

They are both chrysanthemic acid esters of (5-benzylfuran-3-yl)methanol (Elliott alcohol, 1) [15]. Patented methods [16] for the industrial preparation of Elliotf s alcohol are demanding or such as to be hardly exploited in industrial-scale plants. For instance, in one of these methods [17] (5-benzyl-3-furyl)methanol is obtained by a sequence of Claisen condensation of benzyl cyanide and a dialkyl succinate, hydrolysis, esterification, protection of the ketone group, formylation, cyclization to 5-benzyl-3-furfuryl ester and reduction to alcohol with lithium aluminium hydride. 

A log K units. As might be expected, the second dissociation constant of the succinic acid is greater than those of the dialkyl succinic acids. The irans-carboxyl configuration of the first ion is the most... 

Quermann, R., Maletz R., Schafer, H. J. (1993). Conversion of fatty acid methyl esters into dialkylated succinic esters by oxidative coupling of their enolates, Liebigs Ann. Chem., p. 1219. 

Today two commercial synthetic routes are available for the manufacture of quinacridone pigments and some substituted derivatives. The key starting material in either synthesis is dialkyl sucdnoylsucdnate (7), which is synthesized from dialkyl succinate in the presence of a sodium alkoxide catalyst, usually sodium methoxide. The first step is a Claisen condensation, and this is followed by a Dieckman cydization, yielding the disodium salt 8, which upon addification yields 7 (Scheme 18-2)1 1... 

One reaction of dialkyl succinate—namely, Stobbe condensation—has played a key role in the synthesis of important pharmaceuticals. The reaction involves a base-catalyzed condensation of aldehydes or ketones with succinate esters 3 to yield itaconic acid derivatives Numerous pharmaceutical... 

The dialkyl succinates are good plasticizers for vinyl chloride polymers and copolymers and for cellulose derivatives. SA is also used in the manufacture of alkyd resin to impart flexibility, elasticity, and water resistance. " In addition, it finds numerous applications in the field of adhesives, elastomers, lubricants, pharmaceuticals, pesticides, and epoxy and other resins. Succinic acid is also used as a food acidulant and has been placed on the GRAS (generally regarded as safe) list by the FDA. ... 

Michael addition to maleates, 66 Dialkyl alkoxysuccinates, maleates in synthesis, 229 Dialkyldisulfides, adduct with MA, 52 Dialkyl o, )3-epoxysuccinate, from fumarate epoxidation, 69 Dialkyl succinates... 

Unsaturated half acid esters such as 1 are readily prepared by Stobbe condensation between dialkyl succinate and an aldehyde. Johannes G. de Vries of DSM and Floris P. J. T. Rutjes of Radboud University Nijmegen observed (Adv. Synth. Catal. 2008, 350, 85) that these acids were excellent substrates for enantioselective hydrogenation. Kazuaki Kudo of the University of Tokyo designed Organic Lett. 2008,10,2035) a resin bound peptide catalyst for the transfer reduction of unsaturated aldehydes such as 3, using 4 as the net donor. Note that 5 was produced with high enantiocontrol from 3 that was a 2 1 mixture of geometric isomers. 

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