Reduction of phthalic anhydride

Thiophthalide (452) is the oxo form of l-hydroxybenzo[c]thiophene. It is a stable compound, being intermediate in oxidation level between o-xylene and phthalic acid. It can be formed from o-xylene by oxidation with a mixture of sulfur and water at high temperatures it can also be formed by reduction of phthalic anhydride with H2S + H2 (72AHC( 14)331). It reacts with vinyllithium to form a complex which on hydrolysis undergoes ring expansion to 4,5,6,7-tetrahydro-2//-benzo[c]thiepin-5-one (453), as shown in Scheme 154. 

On the other hand, the reduction of phthalic anhydride to phthalide is simpler. The key step in this synthesis is the electrochemical reduction of ammonium phthalamates... 

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... 

The present procedure is based upon the method of Reissert. Phthalide has also been prepared by reduction of phthalic anhydride, and by bromination of o-toluic acid followed by hydrolysis. ... 

In general, the dissolving metal or electrochemical reductions of acyl halides or acyclic anhydrides are not useful for the preparation of primary alcohols. Such reductions invariably provide acyloin esters, ene-diolate diesters or related species. Cyclic anhydrides may be reduced to give lactones. For example, the reduction of phthalic anhydride at a mercury cathode has been used in the synthesis of phthalide (90%). In general, however, such reduction are not widely employed in synthesis. 

Phthalyl alcohol, HOCH2CeH4CH20H-o. Mol. wt. 138.16, m.p. 64°. Prepared by reduction of phthalic anhydride with lithium aluminum hydride in ether (87% yield). In a novel and efficient synthesis of cyclopropanone hydrate, Grewe and Struve used the o-xylylene acetal protective group (1) and, after elimination of... 

Partial reduction of phthalic anhydride (83) is a reliable method of ensuring chemoselectivity (cf. Chapter 5). As often with aldehydes, it is easier to reduce to the alcohol and reoxidise. Amide (81) doesn t react with hydrazine, but the chloride (84) does. 

Scheme 9.114. A representation of the reduction of phthalic anhydride (benzene-1,2-dicarboxylic acid anhydride) to the corresponding lactone with zinc (Zn) in ethanoic acid (acetic acid).

The analgesic and anti-inflammatory Indoprofene (42) can be made by several routes, two of which involve cyclisations. Treatment of phthalic anhydride with amino acid (43) gives imide (45) in one step - the cyclisatlon of (44) must be faster than the inter-molecular reaction by which it is formed. Reduction of (45) give.s Indoprofene as the reactive imide is easily reduced as far as the unreactive amide. 

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. 

Selective reduction at a Pb cathode in H2S04 of phthalic anhydride (1) to... 

In addition to oxidation and reduction reactions, naphthalene readily undergoes substitution reactions such as nitration, halogenation, sulfonation, and acylation to produce a variety of other substances, which are used in the manufacture of dyes, insecticides, organic solvents, and synthetic resins. The principal use of naphthalene is for the production of phthalic anhydride, CgbLO,. 

N-Substituted phthalimides are easily synthesized via solvent-free condensation of phthalic anhydrides with amines or via coupling methods [3]. The phthalimide moiety has a reversible reduction potential in dimethylformamide (DMF) which is... 

Solution As we shall see in Chapter 8, the copolymerization of maleic anhydride and styrene shows a strong tendency toward alternation (ri rj = 0.06). Consequently, a maleic anhydride-based unsaturated polyester cross-hnked with styrene forms a large number of short cross-links, resulting in a rigid polymer. With the addition of phthalic anhydride, the tendency toward alternation is reduced due to the occasional intervention of phthahc anhydride. The reduction of cross-link density results in a less rigid polymer. 

More than 10 years after the establishment of the acetalization process, electrochemists at BASF have searched for a compatible reductive process that can be run instead of the hydrogen evolution. What they have found is the reduction of phthalic acid dimethylester to phthalide [8] (Fig. 2). Phthalide is a compound that was up till then generated by classical catalytic hydrogenation from phthalic acid anhydride [7]. Part of the process development has been to fit the paired electrosynthesis in the same capillary gap cell like the acetalization of the toluene derivatives. 

More generally, reduction of cyclic anhydrides such as phthalic anhydride (benzene-1,2-dicarboxylic acid anhydride) with zinc (Zn) in ethanoic acid (acetic acid, CH3CO2H) results in the formation of cyclic esters (lactones) (Scheme 9.114). As shown, the zinc (Zn) metal is oxidized (to zinc oxide [Zn02]), while the... 

The method of Leupold was used to prepare 3-( -nitrobenzyli-dene)phthalide in a 42% yield by the condensation of phthalic anhydride with 2 -nitrophenylacetic acid in the presence of potassium acetate m.p. 227-229 C (lit m.p. 222 C). The nitro compound was reduced by the conventional stannous chloride reduction to give 3-(p -aminobenzylidene)phthalide in a 64% yield. Recrystallization from aqueous acetone gave pale yellow needles m.p. 233 C. 

The terephthalate plasticizer DEHTP, first commercialized around 1975 as Eastman DOTP, is very similar in structure to DEHP except that the substitution of the aromatic ring is at the 1,4 position versus the 1,2 position of the aromatic ring. The structure of DEHTP is also shown in Pig. 24.1. Terephthalates are prepared by the esterification of terephthaUc acid or by the transesterification of dimethyl terephthalate with aliphatic alcohols such as butanol or 2-ethyl hexanol. Although DEHTP can be produced from terephthalic acid in a traditional DEHP esterification plant with minor modifications to the process, this process is not as efficient as the esterification of phthalic anhydride and manufacturing capacity reductions of >50% are realized. Transesterification of dimethyl terephthalate is a much faster reaction. However, this process will require significant process modifications to a traditional DEHP manufacturing unit. One benefit with this chemistry is that it does not lead to a significant drop in production capacity. The main problem with this route is the limited availability of dimethyl terephthalate in many locations. 

An isoindol1 none moiety forms part of the aromatic moiety of yet another antiinflammatory propionic acid derivative. Carboxylation of the anion from -nitro-ethylbenzene (45) leads directly to the propionic acid (46). Reduction of the nitro group followed by condensation of the resulting aniline (47) with phthalic anhydride affords the corresponding phthalimide (48). Treatment of that intermediate with zinc in acetic acid interestingly results in reduction of only one of the carbonyl groups to afford the isoindolone. There is thus obtained indoprofen (49). ... 

Phthalic anhydride initially reacts with ammonia, which in turn is liberated, for instance, by decomposition of urea. Diiminophthalimide is then produced via phthalimide and monoiminophthalimide. Subsequent self-condensation (as in the phthalonitrile process) under cleavage of ammonia affords polyisoindolenines, which form complexes with copper ions. Ring closure is achieved through further release of ammonia, and copper phthalocyanine is finally obtained by reduction. 

Popper and Bariska (1972) studied the moisture sorption properties of wood chemically modified with acetic (or phthalic) anhydride and analysed the results using Brunauer-Emmett-Teller (BET) theory and the H-H model. Acetylation was found to reduce the number of sorption sites, whereas little effect was noted with phthaloylation. By dividing the sorption isotherm into a monolayer component and a multilayer component using the H-H model, it was shown that there was a large reduction in the... 

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