Succinic acid derivatives

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

When the 1-position is substituted, 3- and 5-aminopyrazoles react at the C-4 carbon atom, the reactivity of which is enhanced by the amino group. Thus pyrazolo[3,4-Z ]pyridines (545) are obtained either by the Skraup synthesis or from 1,3-diifunctional compounds. Here also aminopyrazolinones have been used instead of aminopyrazoles to prepare (545 R = OH). If 1,4-ketoesters (succinic acid derivatives) are used instead of /3-ketoesters, pyrazolo[3,4-Z ]azepinones (546) are obtained. 

Compounds containing carboxyl groups on adjacent carbons (succinic acid derivatives) can be bisdecarboxylated with lead tetraacetate in the presence of O2 263 jjjg reaction is of wide scope. The elimination is stereoselective, but not stereospecific (both meso- and dl- 2,3-diphenylsuccinic acid gave trans- stilbene) a concerted mechanism is thus unlikely. The following mechanism is not inconsistent with the data ... 

Scheme 15.16 Regioselective hydrogenation of an unsymmetrical succinic acid derivative.

Fig. 24.14 Succinic acid derivatives produced by phospho-lane-Rh-catalyzed hydrogenation (X=H, Na or R3NH).

The second relevant set of data is for the formation of the anhydride from substituted succinic acid derivatives. Equilibrium constants for the formation of the anhydride from the acid are available for the various methyl-substituted compounds (Table A.l) and the derived EM s are compared in Table 5 with those for intramolecular nucleophilic catalysis in the hydrolysis of half-esters... 

Succinic acid derivatives antibiotics, amino acid and... 

In addition, 2-substituted chiral succinic acid derivatives can be obtained via diastereoselective radical addition of 2-dioxolanyl radicals to ftimaric acid diamides with a de up to 98% (Scheme 19) [25],... 

The synthesis of succinic acid derivatives, /3-alkoxy esters, and a,j3-unsaturated esters from olefins by palladium catalyzed carbonylation reactions in alcohol have been reported (24, 25, 26, 27), but full experimental details of the syntheses are incomplete and in most cases the yields of yS-alkoxy ester and diester products are low. A similar reaction employing stoichiometric amounts of palladium (II) has also been reported (28). In order to explore the scope of this reaction for the syntheses of yS-alkoxy esters and succinic acid derivatives, representative cyclic and acyclic olefins were carbonylated under these same conditions (Table I). The reactions were carried out in methanol at room temperature using catalytic amounts of palladium (II) chloride and stoichiometric amounts of copper (II) chloride under 2 atm of carbon monoxide. The methoxypalladation reaction of 1-pentene affords a good conversion (55% ) of olefin to methyl 3-methoxyhexanoate, the product of Markov-nikov addition. In the carbonylation of other 1-olefins, f3-methoxy methyl esters were obtained in high yields however, substitution of a methyl group on the double bond reduced the yield of ester markedly. For example, the carbonylation of 2-methyl-l-butene afforded < 10% yield of methyl 3-methyl-3-methoxypentanoate. This suggests that unsubstituted 1-olefins may be preferentially carbonylated in the presence of substituted 1-olefins or internal olefins. The reactivities of the olefins fall in the order RCH =CHo ]> ci -RCH=CHR > trans-RCH =CHR >... 

Polymer Catalyst or Initiator Succinic acid derivative obtained by ozonolysis of the polymer ... 

Biotin can be produced commercially by using, for starting the synthesis, meso-diamino succinic acid derivative of fumaric acid. 

Succinic Acid Derivatives and Amide-derived Carbanions... 

Schemes.13. Alkylation of substituted succinic acid derivatives [128-131].

The strategy for the development of products from biomass needs to be twofold. One approach is to identify those opportunities where we can compete economically with existing petrochemical products. Succinic acid-derived materials fit into this category (Fig. 1). The second approach must include the identification of products with novel functionality that cannot easily or cost effectively be derived from petrochemical building blocks. The challenge with developing new materials is that the market for these products must also be developed and the time and cost can be significant however, the reward may also be substantial. 

As shown in Table 4, the real promise of succinic acid lies in its derivatives. A DOE-funded collaboration among Oak Ridge National Laboratory Argonne National Laboratory Pacific Northwest National Laboratory National Renewable Energy Laboratory and Applied CarboChemicals, Inc. investigated succinic acid derivatives such as tetra-hydrofuran, 1,4-butanediol, y-butyrolactone, and N-methyl pyrrolidone. More recently, Applied Carbochemicals has pursued succinate salts that can serve as de-icers and herbicide additives (40,41). 

Potential Near-Term Succinic Acid Derivatives (39,40,43-46)... 

Much effort has been devoted to the optimization of the polyesterification reaction. For instance, different types of monomeric precursors structurally related to succinic acid (e.g., dimethyl succinate or succinic anhydride) were used. Different kinds of catalysts (e.g., phenolates, titanium alkoxides, tin octanoates) at different concentrations were studied. Different reaction temperatures (130-190 °C) were reached and different procedures for water elimination (vacuum drying under different conditions or toluene distillation) were adopted. Experimental results obtained showed that the use of different catalysts and different monomer precursors (succinic acid derivatives) did not significantly alter the polymerization kinetics or yield, and for this reason, they were abandoned. The procedure finally adopted is summarized below. 

Succinic acid is a potential platform chemical that is expected to be commercialised in a few years. Although the production capacity of petrochemically derived succinic acid is on the scale of 15 000 tonnes per year (Zeikus etal., 1999), the production capacity of succinic acid derivatives is over 270 000 tonnes per year (Willke and Vorlop, 2004). Fermentative production of succinic acid could offer a viable route to bulk chemical production. Figure 4.4 presents potential routes for chemical production from succinic acid (McKinlay et al., 2007). Another advantage of succinic acid microbial production is the simultaneous requirement for CO2 consumption, which reduces the emission of the most important greenhouse gas and makes fermentative succinic acid production a process of significantly low environmental impact. 

The cyclization of carbamic acid 34 into NCA was supposed to correspond to an equilibrium constant that would not be very different from the values reported for the cyclization of succinic acid derivatives 36 (Kcyc = 0.7 x 10-5 and 4 x 10 5 for R = H and Me, respectively [216]). The value of Kcyc = 1 x 10-5 was therefore selected for carbamic acid 34. 

Unsymmetrically substituted succinic acid derivatives can be prepared by reaction of carboxylic acid dianions with lithium a-iodocarboxylates (40-70% yield). 

R = OH). If 1,4-ketoesters (succinic acid derivatives) are used instead of /3-ketoesters. 

Related alkylation chemistry of (2) has provided a route to chiral succinic acid derivatives (11) (eq 7). In this chemistry, acetyl complex (2) was used to produce a succinoyl complex which was subsequently deprotonated a to the ester and alkylated with primary and secondary alkyl halides. This sequence of reactions has been used to produce the succinate fragment of actinonin, as... 

Combination of the reagents TiCU, BuaN, and TMSOTf, was reported to be effective for Claisen condensation, as exemplified in Eqs (42) and (43) [129]. When acyl-oxazolidinones were subjected to reaction with TiCU and a tertiary amine, homocoupling reaction at the a-position of the acyl group took place to give succinic acid derivatives [146], The lithium enolate of an ester or amide has been alkylated with an (N,C>)-acetal in the presence of Ti(0-/-Pr)4 (Eq. 44) [147,148]. 

Dibenzylidene succinic acid derivatives are examples of substrates with a direct link between the a-carbons. Voltammetry of dimethyl dibenzylidenesuccinate shows two reduction peaks separated by 200 mV, and preparative-scale reduction under a variety of conditions gave none of the cyclobutane derivatives expected from intramolecular cyclization. Monomeric products (2 F or 4 F depending on the working potential) were found together with varying amounts of oligomers [122],... 

The l-oxopyrrolo[l,2-fl]quinazoline 155 was obtained by Juneja et alP on heating of the succinic acid derivative 154 in acetic acid. 

PIFA easily converts succinic acid derivatives (32) to -alanine derivatives (33). Limited use of PIFA (1 equiv.) allows the rearrangement of 3-cyclohexene-1-carboxamide (34) without oxidation of the double bond, as shown in Scheme 12. Cyclohexanone is obtained by the PIFA oxidation of 1-cyclohex-enecarboxamide (35). Selective oxidation of the primary amide (36) occurs without effect on secondary or tertiary amides in the same molecule. The rearrangement of the cyclopropane derivative (37) accompanies the ring cleavage to give the -alanine derivative (38) after treatment with benzyloxycarbonyl chloride. ... 

Rearrangement of 3-alanine and succinic acid derivatives (100 and 102) gives l-acyl-2-imidazolidin-ones (101) and 3-alanine derivatives (103) respectively (Scheme 22). However, the -methylcarbox-... 

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