Succinimides, synthesis

Succinimide synthesis.3 Reaction of 2-phenylazirine (1) and Mo(CO)6 (1 equiv.) with diethyl sodiomalonate furnishes the succinimide 2 in 46% yield. This reaction is applicable generally to 2-aryl-substituted azirines and carbanions of 0-dicarbonyl com-... 

Derivatives of polyisobutylene (6. in Figure 9.1) offer the advantage of control over the molecular weight of the polyisobutylene obtained by cationic polymerization of isobutylene. Condensation on maleic anhydride can be done directly either by thermal activation ( ene-synthesis reaction) (2.1), or by chlorinated polyisobutylene intermediates (2.2). The condensation of the PIBSA on polyethylene polyamines leads to succinimides. Note that one can obtain mono- or disuccinimides. The mono-succinimides are used as... 

Halogen-substituted succinimides are a class of products with important appHcations. /V-Bromosuccinimide [128-08-5] mp 176—177°C, is the most important product ia this group, and is prepared by addition of bromine to a cold aqueous solution of succinimide (110,111) or by reaction of succinimide with NaBr02 iu the presence of HBr (112). It is used as a bromination and oxidation agent ia the synthesis of cortisone and other hormones. By its use it is possible to obtain selective bromine substitution at methylene groups adjacent to double bonds without addition reactions to the double bond (113). 

The succinimide derivative (234) can be used in peptide synthesis for conversion of amino acids into their succinimide esters (235 Scheme 41) (79CL1265). 3-Substituted mercapto-1,2-benzisothiazole 1,1-dioxides (236) have been recommended as an odourless means of storage of thiols. The latter are readily regenerated by the action of piperidine (81CL1457). 

Succinimides — see also Pyrrolidine-2,5-diones as anticonvulsants, I, 166 synthesis, 4, 120 Succinimides, N-hydroxy-polymerization, I, 271-272 Sudoxicam... 

The Bnpeoc group was developed as a base-labile protective group for solid-phase peptide synthesis. The carbamate is formed from the O-succinimide (DMF, 10% Na2C03 or 5% NaHC03) and is cleaved using DBN, DBU, DBU/AcOH, or piperidine. ... 

The cyclized analog of meralluride is prepared by a similar synthesis. Thus, condensation of camphoric acid (42) (obtained by oxidation of camphor) with ammonia gives the bicyclic succinimide (44). Reaction with allyl isocyanate followed by ring opening and then reaction with mercuric acetate affords the mercury derivative (45) as the acetate rather than the hydroxide as above. Reaction with sodium chloride converts that acetate to the halide (46). Displacement on mercury with the disodium salt of thioglycollic acid affords the diuretic mercaptomerine (47). ... 

Alpert has shown [47] that poly(succinimide)-silica can be further hydrolyzed to poly (aspartic acid)-silica or condensed with [3-alanine in aqueous solution to form a covalently bonded copolymer of 2-carboxyethyl aspartamide and aspartic acid. The content of carboxyl groups generated by this way has not been quantified directly, but the cation-exchange hemoglobin capacity has been measured for a series of the packings. Thus, the optimal concentration of poly(succinimide) used in the synthesis was found to be 2 5%. 

Scheme 35 Synthesis of succinimides catalyzed by an iron complex...

Sulfur dichloride is difficult to handle it disproportionates readily, has an unpleasant odor, and tends to introduce extra, unwanted chlorine atoms. Several reagents have been developed, especially by Harpp and co-workers, in which these undesirable features have been modified or eliminated. Succinimide-N-sulfenyl chloride (28) and phthalimide-N-sulfenyl chloride (29) are both stable crystalline compounds which undergo many of the reactions of the sulfur dichloride itself. They can, for example, be used in a facile, high yield synthesis of thiiranes from alkenes.33... 

Linz et al.6 report the synthesis of enantiomerically pure cyclosarkomycin 6, a stable crystalline precursor of sarkomycin 5. As described in Scheme 5-3, 6 can be obtained from 8, an asymmetric Diels-Alder adduct of (E )-bromoacry-late. (E)-3-bromoacrylate 9a [the acrylate of (R)-pentolactone 11] and 9b [the acrylate of ( S )-A-methyl hydroxyl succinimide 12] undergo TiCL-mediated Diels-Alder reactions giving 10a or 10b, the endo-product, with high diaster-eoselectivity (Scheme 5-4). With the key intermediate 10a in hand, synthesis of compound 6 is accomplished by following the reaction sequence shown in Scheme 5-5. 

HL Ball, G Bertolini. A-(Chlorobenzyloxycarbonyloxy)succinimide as a terminating agent for solid-phase peptide synthesis application to a one-step purification procedure. Lett Pept Sci 2, 49, 1995. 

It was originally thought that one should be able to remove the succinic acid group by treatment of 7 with hydrazine in the same way one is able to produce a primary amine by treating a phthalimide with hydrazine in the classical Gabriel synthesis (12). This was not the case, though, since 7 did not react with hydrazine. However, it was found that treatment of 7 with dilute sodium hydroxide readily hydrolyzed the succinimide to produce the amino alcohol, 1, in 90% yield and having a 98 - 99% ee. 

The action of phosphorus halides on pyrrolinones and related compounds offers an alternative route to chloropyrroles. Yields of around 60% of 2,5-dichloropyrroles were obtained in this way from N-substituted succinimides (82ZC126). Vilsmeier reaction of N-alkylsuccinimidals formed chlorinated pyrrole aldehydes in modest yields (90CJC791), and there are other examples [66YZ158 81H(15)547]. A useful synthesis of chloropyrrole-2-carboxylates employed the action of phosphorus pentachloride on pyrrolidin-2-one-5-carboxylates (40) (87CB45) (Scheme 15), and in a Pummerer-type reaction pyrrol-3-yl sulfoxides were transformed by thionyl chloride into chloropyrroles. Yields were increased to >80% by the use of oxalyl chloride (88JOC2634) (Scheme 15). 

Regioselective reduction of a succinimide intermediate for a (-i-)-heliotridine synthesis [269] must be due to the influence of the acetoxy group. It is conjectured that the a-a array of the intervening carbon atoms activates the carbonyl. Steric effects should he minimal on the choice of the two sites. 

In 1996, a group from Sandoz (now part of Novartis) reported their synthesis of fexofenadine (3). Cbz protection of commercially available ethyl piperidine-4-carboxylate (34) was achieved using Af-(benzyloxycarbonyloxy)succinimide to afford 35. Treatment of 35 with three equivalents phenyl magnesium bromide led to tertiary alcohol... 

On the other hand, l,3-oxazine-2,6-diones can be formed from /3-aminoacids and phosgene (52USP2600596), or from succinimides and sodium hypochlorite (Scheme 106) (61MI22700). The synthesis of the corresponding 4,6-diones is achieved by the reaction of... 

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