Succinimide analog

It has the reputation for being the most effective succinimide analog in petit mal therapy. It acts by suppressing the EEC pattern of petit mal epilepsy perhaps by depression of the motor cortex and raising the convulsive threshold. Combined drug therapy with either phenobarbital or phenytoin sodium is common in cases where petit mal co-exists with grand mal or other types of epilepsy. 

This Fmoc analog is prepared from the chloroformate, O-succinimide, or p-nitrophenyl carbonate and is cleaved with 10% piperidine in 1 1 6M guanidine/IPA. It was designed to interact strongly on a column of porous graphitized carbon so as to aid in the purification of peptides after cleavage from the resin. 

In a more recent study on 1,3-dipolar cycloaddition reactions the use of succi-nimide instead of the oxazolidinone auxiliary was introduced (Scheme 6.19) [58]. The succinimide derivatives 24a,b are more reactive towards the 1,3-dipolar cycloaddition reaction with nitrone la and the reaction proceeds in the absence of a catalyst. In the presence of TiCl2-TADDOLate catalyst 23a (5 mol%) the reaction of la with 24a proceeds at -20 to -10 °C, and after conversion of the unstable succinimide adduct into the amide derivative, the corresponding product 25 was obtained in an endojexo ratio of <5 >95. Additionally, the enantioselectivity of the reaction of 72% ee is also an improvement compared to the analogous reaction of the oxazolidinone derivative 19. Similar improvements were obtained in reactions of other related nitrones with 24a and b. 

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). ... 

A series of bonded poly(alkyl aspartamide) coatings was prepared on silica by analogy to the method described above. Poly(succinimide) coating was reacted with n-alkyl- and arylalkylamines in dimethylformamide to yield a series of hydrophobic adsorbents. Poly(propyl aspartamide)-silica (PolyPROPYL A) showed the maximal reversible hydrophobic binding of hemoglobin among the Cl -C5... 

Malcin- und Fumarsaurc werden an Blei-Kathoden (in 5%iger Schwefelsaure) in sehr hohen Ausbeuten zu Bernsteinsdure reduziert6. Analog erhalt man Succinimid in salzsau-rer Kochsalz-Losung aus Maleinsaure-imid7. 

Analog erhalt man aus N-Methyl-bis-[benzyliden]-succinimid N-Methyl-3-benzyl-2-benzyliden- und N-Methyl-2,3-dibenzyl-succinimid1. 

This reaction is analogous to 10-16. Primary and secondary alcohols can be converted to alkyl aryl sulfides (ROH RSAr) in high yields by treatment with BU3P and an V-(arylthio)succinimide in benzene. Thioethers RSR can be prepared from an alcohol ROH and a halide R Cl by treatment with tetra-methylthiourea Me2NC(=S)NMe2 followed by NaH. ... 

N-Trimethylsilylamides or lactams 344 react with sodium trimethylsilanolate 96 to generate the anhydrous N-sodium salts 345 and hexamethyldisiloxane 7 in practically quantitative yield [125]. Likewise, silylated succinimide 201 is converted by sodium trimethylsilanolate 96 into hexamethyldisiloxane 7 and the anhydrous sodium salt 346, which reacts with aldehydes RCHO (R=C2H5, n-C Hy), in the presence of catalytic amounts of 96 to give, via 346, the silylated adducts 347 in 43-62% yield [125]. The imide chloride 348 gives, analogously, sodium chloride and 7 and the N-sodium salt 349, which condenses in situ with unreacted imide chloride 348 to give 91% of the amidine 350 [126] (Scheme 4.46). 

Analogously, when the reaction of iV-(phenylseleno)phthalimide or TV-(phenylseleno) succinimide with 3 is carried out in methylene chloride in the presence of 2-3 equivalents of water, compound 175 can be obtained in high yield (equation 141)16. A mixture of isomeric cyclic ethers 175 and 176 was obtained also by treatment of 3 with phenylse-lenocyanide, in the presence of copper(II) chloride (equation 142)143. 

Use of acetophenone rather than benzaldehyde in the Knoevnagel condensation reaction affords the unsaturated ester, 13. Elaboration of this to the succinimide by a scheme analogous to that above leads to the anticonvulsant agent methsuximide (14)... 

Succinimides, e.g., cis- and /ra .r-3,4-dimethylpyrrolidine-2,5-dione 1, show virtually the same behavior as their anhydride analogs the H-3 chemical shifts are 3.12 and 2.68 ppm, respectively 502. The pyrrolidinium salts 2 have been studied in mixtures of diastereomeric cis j trans pairs504. 

Enholm [26] has reported the first examples of asymmetric radical cy-clizations on soluble polymer supports. The stereocontrol element employed consists of a (+)-isosorbide group attached by a 4-carbon chain to each subunit of a soluble succinimide-derived ROMP backbone. Treatment of the radical cychzation substrate 162 with tributyltin hydride in the presence of zinc chloride followed by hydrolysis of the resulting polymer-supported ester 163 gave the desired product 164 in 80% yield and > 90% ee (Scheme 38). The use of alternative Lewis acids, such as magnesium bromide etherate and ytterbiiun (III) triflate, resulted in lower enantioselectivities, 84% and 72% respectively. No such decrease in selectivity was observed in analogous reactions carried out off-support [27], suggesting that the polymer backbone is somehow responsible for this phenomenon. 

As a result of an extensive study, it has been found that methylene groups are attacked much more readily than a methyl group. For example, 2-methyl-2-butene requires 16 hours for completion of the reaction, whereas, 2-methyl-2-hexene requites 10 minutes. The conversion of cyclohexene to 3-broraocyclohexene is accomplished in 20 minutes in 87% yield. It is noteworthy that the bromination of 1-octene with N-btomo-succinimide yields a mixture of l-bromo-2-octene and 3-bromo-1-octene and that the proportion of these isomers is in close agreement with the equilibrium mixture formed at 100° by analogous bromides. ... 

Succinimides and maleimides are accessible via processes analogous to those described for the corresponding anhydrides (see Section 9.4.3.3). Reactions of (COD)2Ni° with either alkenes or alkynes and isocyanates (i.e. heterocumulene analogs of CO2) give azametallacycles that upon carbonylation yield cyclic imides. With alkenes high yields of metallacycles are formed m both simple isocyanates as well as a,(o-diisocyanates. Carbonylation yields are variable, however (Scheme 18). Alkynes give lower metallacycle yields but high yields of die final imide (Scheme 19). ... 

The first documented example of a ring-expansion reaction involving a sub-phthalocyanine came in 1990. Here, Kobayashi and Osa and coworkers reported that by treating the t-butyl-substituted subphthalocyanine 2.286 with succinimide (2.296), one could obtain the unsymmetrically substituted phthalocyanine 2.297 in 13% yield (Scheme 2.3.5). Similarly, treating subphthalocyanine 2.286 with the dii-minoisoindoline analogs 2.298-2.300, afforded the unsymmetrically substituted... 

This is analogous to the formation of succinimide from succinic anhydride fp. 284). 

This five membered hetero-cyclic compound is analogous to the two preceding ones having the oxygen of furfuran replaced by the imide group, (—NH—). Two methods of synthesis prove its constitution. Succinimide when distilled with sodium or zinc dust is reduced and pyrrole is obtained. 

---