Sodium phthalimide

Tributylvinylphosphonium bromide forms the betaine 213 with sodium phthalimide. Addition of aldehydes RCHO (ketones are inert) gives almost exclusively the ( )-allylphthalimides 214, which form the corresponding allylamines by cleavage with hydrazine210. 

Sodium phthalimide may be prepared in a similar manner, the yield being 50% theoretical. 

It is prepared by the action of sodium hydroxide and sodium hypochlorite on phthalimide (Hofmann reaction). When heated with soda lime it gives aniline. 

Benzylatnine. Warm an alcoholic suspension of 118-5 g. of finely-powdered benzyl phthalimide with 25 g. of 100 per cent, hydrazine hydrate (CAUTION corrosive liquid) a white, gelatinous precipitate is produced rapidly. Decompose the latter (when its formation appears complete) by heating with excess of hydrochloric acid on a steam bath. Collect the phthalyl hydrazide which separates by suction filtration, and wash it with a little water. Concentrate the filtrate by distillation to remove alcohol, cool, filter from the small amount of precipitated phthalyl hydrazide, render alkaline with excess of sodium hydroxide solution, and extract the liberated benzylamine with ether. Dry the ethereal solution with potassium hydroxide pellets, remove the solvent (compare Fig. //, 13, 4) on a water bath and finally distil the residue. Collect the benzylamine at 185-187° the 3ueld is 50 g. 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

Phthalide. In a 1 litre bolt-head flask stir 90 g. of a high quality zinc powder to a thick paste with a solution of 0 5 g. of crystallised copper sulphate in 20 ml. of water (this serves to activate the zinc), and then add 165 ml. of 20 per cent, sodium hydroxide solution. Cool the flask in an ice bath to 5°, stir the contents mechanically, and add 73-5 g. of phthalimide in small portions at such a rate that the temperature does not rise above 8° (about 30 minutes are required for the addition). Continue the stirring for half an hour, dilute with 200 ml. of water, warm on a water bath imtil the evolution of ammonia ceases (about 3 hours), and concentrate to a volume of about 200 ml. by distillation vmder reduced pressure (tig. 11,37, 1). Filter, and render the flltrate acid to Congo red paper with concentrated hydrochloric acid (about 75 ml. are required). Much of the phthalide separates as an oil, but, in order to complete the lactonisation of the hydroxymethylbenzoic acid, boil for an hour transfer while hot to a beaker. The oil solidifles on cooling to a hard red-brown cake. Leave overnight in an ice chest or refrigerator, and than filter at the pump. The crude phthalide contains much sodium chloride. RecrystaUise it in 10 g. portions from 750 ml. of water use the mother liquor from the first crop for the recrystaUisation of the subsequent portion. Filter each portion while hot, cool in ice below 5°, filter and wash with small quantities of ice-cold water. Dry in the air upon filter paper. The yield of phthalide (transparent plates), m.p. 72-73°, is 47 g. 

Methyl chloride can be converted iato methyl iodide or bromide by refluxing ia acetone solution ia the presence of sodium iodide or bromide. The reactivity of methyl chloride and other aUphatic chlorides ia substitution reactions can often be iacteased by usiag a small amount of sodium or potassium iodide as ia the formation of methyl aryl ethers. Methyl chloride and potassium phthalimide do not readily react to give /V-methy1phtha1imide unless potassium iodide is added. The reaction to form methylceUulose and the Williamson synthesis to give methyl ethers are cataly2ed by small quantities of sodium or potassium iodide. 

Propenylphenoxy compounds have attracted much research. BMI—propenylphenoxy copolymer properties can be tailored through modification of the backbone chemistry of the propenylphenoxy comonomer. Epoxy resins may react with propenylphenol (47,48) to provide functionalized epoxies that may be low or high molecular weight, Hquid or soHd, depending on the epoxy resin employed. Bis[3-(2-propenylphenoxy)phthalimides] have been synthesized from bis(3-rutrophthalimides) and o-propenylphenol sodium involving a nucleophilic nitro displacement reaction (49). They copolymerize with bismaleimide via Diels-Alder and provide temperature-resistant networks. 

In a typical experiment, triethylene glycol was treated with two equivalents of sodium toluenesulfonamide in dry DMF solution. After 6 h at reflux, the solution was distilled and product obtained by a standard work-up procedure. By this procedure, 9 was obtained in about 10% yield. The transformation is illustrated below as Eq. (4.10). Note also that Vogtle and his coworkers have also utilized phthalimide as a source of nitrogen in the preparation of such azacrown precursors as H2N(CH2CH2 0)2CH2CH2NH2 In such reactions, a standard hydrazine cleavage was used to remove the phthaloyl residue. 

The Gabriel-Colman reaction has been used to prepare 3-alkyl isoquinoline 1,4-diols. Phthalimides 8 and 9 rearrange as expected when treated with alkoxides. Further treatment with sodium ethoxide results in decarboxylation and the expected isoquinolinone 1,4-diols 12 and 13. 

The Gabriel-Colman reaction can be used to prepare isoquinoline-1,4-diols regioselectively by the use of unsymmetrically substituted phthalimides. Reaction of phthalimide 32 with sodium ethoxide in ethanol provides a 1 7 mixture of 33 34. It was rationalized that attack at carbon b is preferred because of its greater steric accessibility and diminished electron density compared to carbon a. In spite of the reasonable regioselectivity observed m this reaction, the Gabriel-Colman reaction has not been substantially investigated in the preparation of non-symmetrically substituted isoquinolines. 

Dissolve 0 6 g. of the primary amine and 0-6 g. of pure phthalic anhydride in 6 ml. of glacial acetic acid and reflux for 20-30 minutes. (If the amine salt is used, add 1 g. of sodium acetate.) The N-substituted phthalimide separates out on cooling. RecrystaUise it from alcohol or from glacial acetic acid. 

On the other hand, the reaction of 3-,sec-aminophenols (71) with phthalic anhydride does not give the corresponding keto acids (72). The keto acids (72) having a secondary amino group at 4-position are prepared by the reaction of 3-sec-aminophenols (71) with phthalimide at 150-220°C in the presence of boric acid, followed by hydrolysis of the intermediate carboxamide with aqueous sodium hydroxide (Eq. 3). 

Oximes 509 can be converted to their tosylates 510, but use of a large excess of KOH converts them directly into 27/-azirincs 511 (Scheme 82) <2003JOC9105>. The benzotriazolyl moiety in azirines 511 can be substituted by nucleophiles (organomagnesium reagents, potassium phthalimides, and sodium thiophenoxide) to give disubstituted azirines 512. 

These findings did encourage us to examine further the biological properties of the imidazoisoindoles, particularly since their physical properties were also quite different from their phthalimide precursors. The first requirement was an improved procedure for the synthesis of the imidazoisoindoles. A number of reagents, both acidic and basic, were found that would effect cyclization of these phthalimides. One o the most consistent methods utilized sodium hydride in hot toluene or xylene. Some large-scale preparations, e.g. of were successfully run using sodium hydroxide pels in xylene. 

Results of reductions of cyclic anhydrides to lactones with sodium amalgam or with zinc are inferior to those achieved by complex hydrides [1020]. However, 95.6% yield of phthalide was obtained by reduction of phthalimide with zinc in sodium hydroxide [1021]. 

By a very similar series of reactions Sorensen has also synthesised ornithine he first introduces the phthalimide group into the sodium... 

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>. 

In the fully and partially unsaturated oxygenated series, the syntheses of 2,5-dimethoxycarbonyl-3,6-diphenyl-l,4-dioxin 231 and 2,6-dimethoxycarbonyl-3,5-diphenyl-l,4-dioxin 232 were recently reported from methyl phenylchloro-pyruvate with potassium phthalimide and sodium imidazolide <2000CHE911>. 

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. 

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