Phthalimide, hydrogenation

They are formed by heating dibasic acids or their anhydrides with ammonia. The hydrogen atom of the NH group is acidic and can be replaced by a metal. Mild hydrolysis breaks the ring to give the half amide of the acid. See succinimide and phthalimide. 

Another alternative for preparing a primary amine from an alkyl halide is the Gabriel amine synthesis, which uses a phthalimide alkylation. An imide (—CONHCO—) is similar to a /3-keto ester in that the acidic N-H hydrogen is flanked by two carbonyl groups. Thus, imides are deprotonated by such bases as KOH, and the resultant anions are readily alkylated in a reaction similar to the acetoacetic ester synthesis (Section 22.7). Basic hydrolysis of the N-alkylated imide then yields a primary amine product. The imide hydrolysis step is analogous to the hydrolysis of an amide (Section 21.7). 

Bromoethylamine hydrobromide has been prepared by the reaction of potassium phthalimide with ethylene bromide, followed by hydrolysis,1 by the addition of hydrogen bromide to ethyleneimine,2 and by the present method.3... 

The transformation of isoquinoline has been studied both under photochemical conditions with hydrogen peroxide, and in the dark with hydroxyl radicals (Beitz et al. 1998). The former resulted in fission of the pyridine ring with the formation of phthalic dialdehyde and phthalimide, whereas the major product from the latter reaction involved oxidation of the benzene ring with formation of the isoquinoline-5,8-quinone and a hydroxylated quinone. 

Photolysis of a variety of substances including hydrogen peroxide, phthalimide hydroperoxides (104), N-hydroxypyridinethiones (105), pyrimido[5,4-g]pteridinetetrone N-oxides (106), and N-arylalkyl-Af-phenylhydroxylamines (107) has been reported to generate hydroxyl radical in aqueous solutions. ... 

Esters of (V-hydroxyphthalimide can also be used for decarboxylation. Photolysis in the presence of an electron donor and a hydrogen atom donor leads to decarboxylation. Carboxyl radicals are formed by one-electron reduction of the phthalimide ring. 

The phthalide used by the submitters and by the checkers was a commercial product, obtained from E. I. du Pont de Nemours and Company, Wilmington, Delaware. This product is no longer available. Phthalide may be prepared in 82.5 per cent yields by hydrogenation of phthalic anhydride in benzene at 270° under 3000 lb. pressure in the presence of copper chromite 1 or, in yields of 61-71 per cent, from phthalimide according to the procedure given in Org. Syn. 16, 71 Coll. Vol. 2, 1943, 526. 

Asymmetric hydrogenation of 3,4-hydroisoquinolines with Ir-chiral phosphorus ligand complexes has been studied. Although the highest enantioselectivity to date is obtained with a chiral titanocene catalyst,308,308a 308c chiral BCPM-Ir or BINAP-Ir complexes with additive phthalimide or F4-phthalimide have shown some good selectivity. Some examples are listed in Table 24. 

A very impressive example of the synthetic utility of this chemistry is the one-pot enantioselective double G-H activation reaction of 86 to generate chiral spiran 87 (Equation (73)).172 In this case, the phthalimide catalyst Rh2(enantiotopically selective aromatic C-H insertions of diazo ketoesters (Equation (74)).216 Moreover, dirhodium(n) tetrakisIA-tetrafluorophthaloyl- )-/ /-leucinate], Rh2(hydrogen atoms of the parent dirhodium(n) complex are substituted by fluorine atoms, dramatically enhances the reactivity and enantioselectivity (up to 97% ee). Catalysis... 

In a more complex elaboration of the hydrogen atom abstraction/nucleo-philic cyclization route to tetrahydrofurans (Scheme 20), a carbohydrate-based N-alkoxy phthalimide was converted to a spirocyclic acetal in excellent yield and diastereoselectivity (Scheme 33) [136]. In this cyclization, nucleophilic attack takes place from the endo face of the trioxabicyclo [3.3.0] octane... 

There is normally a considerable difference in acidity of neighboring carboxyl groups due to the formation of one hydrogen bond between the groups. Stable ammonium salts are formed only by stronger acids. An imide, e.g., phthalimide, is formed when the ammonium salts are heated to higher temperatures. 

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]. 

---