Hydrogenation of phthalic anhydride

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. 

Hydrogenation of phthalic anhydride over copper chromite afforded 82.5% yield of the lactone, phthalide, and 9.8% of o-toluic acid resulting from hydrogenolysis of a carbon-oxygen bond [1015]. Homogeneous hydrogenation of a,a-dimethylsuccinic anhydride over tris(triphenylphos-phine)rhodium chloride gave 65% of a,a-dimethyl- and 7% of )S,)S-dimethyl-butyrolactone [1016]. 

McAlees et al. studied the hydrogenation of various phthalic anhydrides over 10% Pd-C in ethyl acetate.62 Hydrogenation of phthalic anhydride gave o-toluic acid in high yield. Either 3- or 4-substituted phthalic anhydrides may give phthalides and/or 2-(hydroxymethyl)benzoic acids in addition to o-toluic acids. In the case of 4-methoxyphthalic anhydride, the product mixture contained 35% of 2-(hydroxymethyl)-... 

Scheme 10.6 Possible intermediates and reaction routes in the hydrogenation of phthalic anhydride over Pd-C.

Metal oxides such as iron oxide were first reported as catalysts for the hydrogenation of carboxylic acids to the corresponding aldehydes by GAP in 1935 [4]. A typical example was the production of benzaldehyde by hydrogenation of phthalic anhydride. After this discovery the success of this system, a variety of catalysts such as y-alumina [5], vanadium oxide [6], manganese oxide [7], yttrium oxide... 

Starting material for the industrial synthesis is phthalide, which may be obtained by hydrogenation of phthalic anhydride. Reaction with o-cresol leads to the corresponding carboxyUc acid, which is converted via its acid chloride into the acyl cyanide. A Pinner reaction and treatment with methoxyamine finally give kresoxim-methyl. [59]... 

A. Preparation of Sec.-Oclyl Hydrogen Phihalate.—A mixture of 130 g. (i mole) of 5ec.-octyl alcohol (Org. Syn. 1, 61) and 148 g. (i mole) of phthalic anhydride is heated for twelve to fifteen hours in a flask surrounded by an oil bath at 110-115° (Note i). During the heating the mixture should be mechanically stirred... 

A 500-ml, three-necked, round-bottom flask is fitted with a mechanical stirrer, a thermometer, and a wide-stern (powder) funnel. The flask is cooled in an ice-salt bath and charged with 125 ml (approx. 0.5 mole) of 15% sodium hydroxide solution. When the stirred solution reaches -10°, 30% hydrogen peroxide (57.5 g, 52.5 ml, approx. 0.5 mole) previously cooled to -10° is added in one portion. The pot temperature rises and is allowed to return to —10° whereupon 37.5 g (0.25 mole) of phthalic anhydride (pulverized) is added rapidly with vigorous stirring. Immediately upon dissolution of the anhydride, 125 ml (approx. 0.25 mole) of cooled (-10°) 20% sulfuric acid is added in one portion. (The time interval between dissolution of the anhydride and the addition of the cold sulfuric acid should be minimized.) The solution is filtered through Pyrex wool and extracted with ether (one 250-ml portion followed by three 125-ml portions). The combined ethereal extracts are washed three times with 75-ml portions of 40% aqueous ammonium sulfate and dried over 25 g of anhydrous sodium sulfate for 24 hours under refrigeration. 

Phenyl indandiones With an acidic hydrogen often interfere with clot formation. When electron withdrawing groups are present in the p-position, acidity is increased and activity goes up. The opposite effect is seen with electron-donating substituents. Synthesized in the usual way, the anticoagulant bromindione (15) results from sodium acetate-catalyzed condensation of phthalic anhydride and p-a-bromophenyl-acetic acid. ... 

The first examples of a homogeneous reduction of this type were reported in 1971. Cobalt carbonyl was found to reduce anhydrides such as acetic anhydride, succinic anhydride and propionic anhydride to mixtures of aldehydes and acids. However, scant experimental details were recorded [94]. In 1975, Lyons reported that [Ru(PPh3)3Cl2] catalyzes the reduction of succinic and phthalic anhydrides to the lactones y-bulyrolaclone and phthalide, respectively [95], The proposed reaction sequence for phthalic anhydride is shown in Scheme 15.15. Conversion of phthalic anhydride was complete in 21 h at 90 °C, but yielded an equal mixture of the lactone, phthalide (TON = 100 TOF 5) and o-phthalic acid, which is presumably formed by hydrolysis of the anhydride by water during lactoniza-tion. Neither acid or lactone were further hydrogenated to any extent using this catalyst system, under these conditions. 

In a i-l. round-bottomed flask, equipped with a mechanical stirrer and cooled in an ice-salt bath, is placed 275 g. (250 cc., approximately 1 mole) of 15 per cent sodium hydroxide solution. This is cooled to —10° (Note 1), and 115 g. (105 cc., approximately 1 mole) of 30 per cent hydrogen peroxide which has been similarly cooled is added in one portion. The heat of reaction causes the temperature to rise markedly. When the temperature has again dropped to — io°, 75 g. (0.5 mole) of phthalic anhydride which has been pulverized to pass a 40-mesh sieve is added as quickly as possible while the contents are stirred vigorously in the freezing mixture (Notes 2 and 3). As soon as all the anhydride has dissolved, 250 cc. (0.5 mole) of 20 per cent sulfuric acid which has been previously cooled to — xo°, but not frozen (Note 4), is added. 

Potassium hydrogen phthalate is prepared by neutralization reaction of phthalic anhydride and potassium hydroxide, followed by crystallization ... 

TAT and TAT-HCl are the most available and inexpensive TNT derivatives [39,43, 44]. Catalytic hydrogenation of TNT led to the formation of free TAT [45]. Treatment of this compound with threefold molar amount of phthalic anhydride led to the formation of 2,4,6-tris(N-phthalimido)-toluene (Scheme 4.17), which under the action of hydrazine hydrate was transformed into 2,4-diamino-6-(N-phthalimido)-toluene (Scheme 4.17) [41],... 

Carboxy carbons of methyl benzoates are shielded by electron-withdrawing substituents in the oposition of the benzene ring [320] (Table 4.38). Carbonyl shifts of phthalic acid diesters and phthalimide are larger than those of phthalic anhydride [321]. fi effects of the O-alkyl group in the esters and hydrogen bonding of the imide are the obvious reasons. 

An attempt to scale up the synthesis of 2-thiophthalide by the reduction of phthalic anhydride with hydrogen sulfide gave 3,3 -bithiophthalide (106a), which arises by condensation of 2-thiophthalide (98) with phthalic thioanhydride (104) (Scheme III).118... 

Monoperphthalic acid has been prepared by hydrolysis of phthalyl peroxide with sodium hydroxide, by reaction of phthalic anhydride with excess alkaline pero.xide solution, by reaction of phthalic anhydride with hydrogen peroxide, and by stirring phthalic anhydride with mildly alkaline peroxide. The method described here is a slight modification of the last procedure. 

The phthaleins and sulfonphthaleins are closely related to the triphenylmethane dyes. Their chief importance is due to their extensive use as indicators in determining the hydrogen concentration of solutions. The simplest of the phthaleins is phenolphthalein, which is formed by the condensation of one mole of phthalic anhydride and two moles of phenol in the presence of a dehydrating agent, such as sulfuric acid or zinc chloride. 

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