Succinic ester-amide

In general, esters, acid chlorides, and anhydrides are most reactive toward the Kulinkovich reagent. Carbonates and thioesters are of moderate reactivity, whereas carbonamides are least reactive. Case in point was made by chemoselective Kulinkovich reaction of succinic ester-amide 12. Cha observed that only the ester portion underwent the Kulinkovich reaction to afford cyclopropanol 13. Szymoniak demonstarted that nitriles are more reactive than ester and amides. 

It then remains to remove protecting groups and release the product from the support. All of these tasks, except for the removal of the dimethoxytrityl group, are achieved by use of a single deprotection reagent, aqueous base (ammonia). The cyanoethyl groups are lost from the phosphates by base-catalysed elimination, and amide protection of the bases is removed by base-catalysed hydrolysis. The latter process also achieves hydrolysis of the succinate ester link to the support. 

Succinic esters of dextran have been prepared and transformed into the corresponding imidazolides, which react smoothly with alcohols or amines to yield the corresponding polymeric esters or amides. These activated amides may be of value for the preparation of polymer-drug adducts with a main backbone degradable to safe metabolites in the body fluids. 

In the electrolysis of cyan-acetic ester the formation of dicyan-succinic ester could not be observed likewise a union of the anions of benzyl-malonic ester, acetyl-malonic ester, and acetyl-dicarboxylic ester did not take place. Electrolysis of acid amides in the... 

Synthesis, structure, and properties of a set of alternating copoly(ester amide)s made from L-tartaric acid, succinic acid, and n-amino-l-alkanols (n=2, 3, and 6) (Figure 8.14) have been studied in order to understand the influence of the heterogeneity introduced in the polymer microstructure from the differences in constitution of succinic and tartaric units [59,60]. These PEAs contained equal amounts of amide and ester groups and were stereoiegular and easily synthesized by the condensation of the p-toluene sulfonate salts of bis(aminoaIkyl) succinates with active esters of tartaric acid. Polymers displayed... 

A. Perez-Rodriguez, A. Alla, J.M. Fern4ndez-Santin, S. Munoz-Guerra, Poly (ester amide)s derived from tartaric and succinic acids changes in structure and properties upon hydrolytic degradation, J. Appl. Polym. Sci. 78 (2000) 486 94. 

A large number of dibasic acids and anhydrides are used in the preparation of poly(ester amide)s. These include terephthalic acid, phthalic anhydride, isophthalic acid, endic endo-cis bicyclo(2,2,10-5)-heptene-2,3-dicarboxylic] anhydride, hydrogenated endic anhydride, maleic anhydride, fumaric acid, dichloromaleic anhydride, itaconic acid, brassylic acid, dimer acid, adipic acid, sebacic acid, succinic acid, trimeUitic anhydride, pyrromellitic anhydride and ethylenediamine tetraacetic acid (EDTA). However, tri- and poly-functional compounds are used only partially and are combined with bifunctional derivatives, or derivatives of previously prepared multifunctional compounds which are subsequently polymerised with bifunctional compounds. 

Synthetic biodegradable polyesters are general made by the pofycondensation method and raw materials are obtained from petrochemical feed stocks. Aliphatic polyesters such as pofy(butylene succinate) and poly( -caprolactone) are cormnercially produced. Besides these ahphatic pofyesters, various types of synthethic biodegradable polymers have been designed [33]. They are, for example, poly(ester amide)s, pofy(ester carbonate)s, pofy(ester urethane)s, etc. Most of them are still at a premature stage. 

Alla, L., Rodriguez-Galan, A., and Munoz-Guerra, S., 2000, Hydrolytic and Enzymatic Degradation of Copoly(ester amide)s based on L-Tartaric and Succinic acids. Polymer 41 6995-7002. 

Property Poly(capro lactone) (PCD Poly(ester amide) (PEA) Poly(butylene succinate/adipate) (PBSA) Polyfbutylene adipate-co-terephthalate) (PBSA) Poly( vinyl alcohol) (PVA)... 

The expected fibre forming properties of poly(ester amide)s makes them suitable as bioresorbable medical sutures. Thus poly(ester amide)s based on a diamine and natural metabolites like glycolic- or lactic acid (Fig. 5.3) have been investigated. The properties of die material could be optimized by the use of water soluble diamide-diols to minimize polymer resorption time. To optimize the polymer melting temperature and in-vivo fibre strength retention succinic acid was used as die comonomer (Barrows, 1980). Alternating poly(ester... 

Alla A, Rodriguez-Galan A, Munoz-Guerra S (2000), Hydrolytic and enzymatic degradation of copoly(ester amide)s based on L-tartaric and succinic acids . Polymer, 41 (19), 6995-7002. 

Fey T, Holscher M, Keul H, Hocker H (2003a), Alternating poly(ester amide)s from succinic anhydride and amino alcohols synthesis and thermal characterisation , Pol. Int., 52 (10), 1625-1632. 

Villuendas I, Molina I, Regano C, Bueno M, Fernandez-Santin J M, Galbis J A, Munoz-Guerra S (1999), Hydrolytic degradation of poly(ester amide)s made from tartaric and succinic acids . Macromolecules, 32 (24), 8033-8040. 

Ethyl oxalate is the only liquid ester which gives this rapid separation of the amide, which is therefore characteristic. Methyl and ethyl formate react rapidly with ammonia, but the soluble formamide does not separate methyl succinate gives crystalline succinamide after about I hour s standing, other esters only after a much longer time. The solid esters, other than methyl oxalate, are either soluble in water and remain so when treated with ammonia, or alternatively are insoluble in water and hence clearly not methyl oxalate. 

Figure. 25.3 Succinimidyl succinate-mPEG may be used to modify amine-containing molecules to form amide bond derivatives. The ester bond of the succinylated mPEG, however, is subject to hydrolysis.

In the hydroxycyclopropanation of alkenes, esters may be more reactive than N,N-dialkylcarboxamides, as is illustrated by the exclusive formation of the disubstituted cyclopropanol 75 from the succinic acid monoester monoamide 73 (Scheme 11.21) [91]. However, the reactivities of both ester- as well as amide-carbonyl groups can be significantly influenced by the steric bulk around them [81,91]. Thus, in intermolecular competitions for reaction with the titanacydopropane intermediate derived from an alkylmagnesium halide and titanium tetraisopropoxide or methyltitanium triisoprop-oxide, between N,N-dibenzylformamide (48) and tert-butyl acetate (76) as well as between N,N-dibenzylacetamide (78) and tert-butyl acetate (76), the amide won in both cases and only the corresponding cyclopropylamines 77 and 79, respectively, were obtained (Scheme 11.21) [62,119]. 

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