Lithium phthalimide

Alkylation ofimutes. Ethyl chloroformale in DMF reacts with lithium phthalimide at temperatures of 60-110° to give N-ethylphthalimide (2) in 80% yield. 

Protected primary allylic amines were generated from allylic carbonates and ammonia equivalents. Iridium-catalyzed allylic substitution has now been reported with sulfonamides [90, 91], imides [89, 91-93], and trifluoroacetamide [89] to form branched, protected, primary allylic amines (Table 5). When tested, yields and selectivities were highest from reactions catalyzed by complexes derived from L2. Reactions of potassium trifluoroacetamide and lithium di-tert-butyhminodi-carboxylate were conducted with catalysts derived from the simplified ligand L7. Reactions of nosylamide and trifluoroacetamide form singly-protected amine products. The other ammonia equivalents lead to the formation of doubly protected allylic amine products, but one protecting group can be removed selectively, except when the product is derived from phthalimide. 

Phthalimide was hydrogenated catalytically at 60-80° over palladium on barium sulfate in acetic acid containing an equimolar quantity of sulfuric or perchloric acid to phthalimidine [7729]. The same compound was produced in 76-80% yield by hydrogenation over nickel at 200° and 200-250 atm [43 and in 75% yield over copper chromite at 250° and 190 atm [7730]. Reduction with lithium aluminum hydride, on the other hand, reduced both carbonyls and gave isoindoline (yield 5%) [7730], also obtained by electroreduction on a lead cathode in sulfuric acid (yield 72%) [7730]. 

A detailed study of the conversion of 3,4-dichloro-l,2,5-thiadiazole into 3,4-diamino-l,2,5-thia-diazole has been carried out <76JHC13>. Reaction with lithium or sodium amide produces only 4% of the diamine together with cyano-containing by-products, a consequence of direct attack on sulfur. Use of a less powerful nucleophile, ammonia or potassium phthalimide, resulted in an increased attack on carbon and produced the diamine in 24% and 66% yields, respectively. Secondary amines, e.g. morpholine <76JOC3l2l> and dimethylamine <72JMC315>, produce the normal displacement products. The reaction of dichlorothiadiazole with potassium fluoride in sulfolane gives a mixture of 3-chloro-4-fluoro and 3,4-difluoro-l,2,5-thiadiazole <82CB2135>. 

Terpoly(amide—imide—urethanes) have been synthesized in yields up to 50—75% by the reaction of 4-carboxy- N-(p-hydroxyphenyl)phthalimide with diisocyanates in A/-methyl-2-pyrrolidinone containing 5% lithium chloride (28). 

Thiiranes can be formed directly and stereospecifically from 1,2-disubstituted alkenes by addition of trimethylsilylsulfenyl bromide, formed at -78 C from reaction of bromine with bis(trimethylsilyl) sulfide (Scheme 7).12 A two-step synthesis of thiiranes can be achieved by addition of succinimide-A/-sulfe-nyl chloride or phthalimide-A -sulfenyl chloride to alkenes followed by lithium aluminum hydride cleavage of the adducts (Scheme 8).13 Thiaheterocycles can also be formed by intramolecular electrophilic addition of sulfenyl chlorides to alkenes, e.g. as seen in Schemes 914 and 10.13 Related examples involving sulfur dichloride are shown in Schemes 1116 and 12.17 In the former case addition of sulfur dichloride to 1,5-cyclooctadiene affords a bicyclic dichloro sulfide via regio- and stereo-specific intramolecular addition of an intermediate sulfenyl chloride. Removal of chlorine by lithium aluminum hydride reduction affords 9-thiabicyclo[3.3.1]nonane, which can be further transformed into bicyclo[3.3.0]oct-1,5-ene.16... 

The addition of ammonia to acrylonitrile gives /S-aminopropionitrile and fczs-(/S-cyanoethyl)-amine. The former is hydrolyzed directly to /S-amino-propionic acid (90%) by barium hydroxide, " and the latter may also be converted through the intermediate phthalimide to the same amino acid (6S)%). A variation of this procedure involves condensation of phthalimide and acrylonitrile to /S-phthalimidopropionitrile, Both amino and carboxyl groups are formed during the subsequent hydrolysis by hydrochloric acid. The free /S-alanine (75%) is liberated from the hydrochloride by lithium hydroxide. ... 

Dihydroisoindole has been prepared from phthalimide by electrolytic reduction and by reduction with lithium aluminum hydride. Other methods that have been used are reduction of 1-chlorophthalazine with zinc and hydrochloric acid and... 

In the acid-catalyzed reactions of orthoformates with primary carbon acid amides or urethanes tris(acylamino)methanes (537 Scheme 98) are formed with good yields. - Dimethylamino-di(phthalimido)methane (531) is accessible from phthalimide and DMF diethyldithioacetal. Lithium di-methylamide, prepared in situ from lithium and dimethylamine in HMPA converts orthoformates to tris(dimethylamino)methane (529). ... 

Treatment of 75 with lithium acetylide ethylenediamine complex afforded the acetylene derivative 78 (85%), which was transformed into the vinyl alcohol 79 by partial hydrogenation using Lindlar catalyst. Employing the Mitsunobu reaction, compound 79 was transformed into the phthalimide 80, which was converted into the benzamide 82 (64%) via the primary amine 81 by sequential deacylation and benzoylation. When the... 

Conditions for the formation of isoindoles by the reduction of phthal-imides have proved difficult to establish. Reduction of phthalimide itself with lithium aluminum hydride gives isoindoline. However, Garmaise and Ryan54 have shown that N-benzylphthalimide can be reduced with a modified hydride reductant [sodium bis(2-methoxyethoxy)aluminum hydride] to give 2-benzylisoindole in moderate yield under mild conditions. 

Addition of organolithium reagents to phthalamidines gives isoindoles with a 1-substituent derived from the lithium compound <79JOC15l9>. The phthalamidines can be prepared in a number of ways, including partial reduction of phthalimides by zinc (Scheme 90). 

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