Phthalic anhydride, hydrolysis

Note that in these three examples involving hydrogen peroxide, chromium trioxide and sodium nitrite, dangerous reactions have been described for carboxyiic acids (see on p.316-317). They all referred to the three following systems acetic acid-/hydrogen peroxide, acetic acid/chromium trioxide and o-phthalic acid/sodium nitrite. One can ask oneself whether the same reactions did not take place after the acetic and phthalic anhydride hydrolysis. 

It was first described in 1608 when it was sublimed out of gum benzoin. It also occurs in many other natural resins. Benzoic acid is manufactured by the air oxidation of toluene in the liquid phase at 150°C and 4-6 atm. in the presence of a cobalt catalyst by the partial decarboxylation of phthalic anhydride in either the liquid or vapour phase in the presence of water by the hydrolysis of benzotrichloride (from the chlorination of toluene) in the presence of zinc chloride at 100°C. 

Chlorendic Acid. Chlorendic acid [115-28-6] and its anhydride [115-27-5] are widely used flame retardants. Chlorendic acid is synthesized by a Diels-Alder reaction of maleic anhydride and hexachlorocyclopentadiene (see CyclopentadlENE and dicyclopentadiente) in toluene followed by hydrolysis of the anhydride using aqueous base (60). The anhydride can be isolated directly from the reaction mixture or can be prepared in a very pure form by dehydration of the acid. The principal use of chlorendic anhydride and chlorendic acid has been in the manufacture of unsaturated polyester resins. Because the esterification rate of chlorendic anhydride is similar to that of phthalic anhydride, it can be used in place of phthalic anhydride in commercial polyester... 

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). 

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. 

Succinic anhydride is clearly hydrogenated more readily than the acid, as was the case with phthalic acid (Scheme 15.17), but faster absolute rates were observed in the hydrogenation of o-phthalic acid and phthalic anhydride to phtha-lide. In these reactions, the problem of anhydride hydrolysis is less significant as the acid can also be reduced to the same lactone product... 

Although anthraquinone is the starting point for the preparation of many derivatives, involving substitution and replacement reactions, certain compounds are obtained directly by varying the components in the above synthesis. Thus, for example, replacement of benzene with methylbenzene (toluene) leads to the formation of 2-methylanthraquinone. A particularly important variation on the phthalic anhydride route is the synthesis of 1,4-dihydroxyanthraquinone (6.6 quinizarin) using 4-chlorophenol with sulphuric acid and boric acid as catalyst (Scheme 6.3). The absence of aluminium chloride permits hydrolysis of the chloro substituent to take place. 

Monoperphthalic acid has been prepared by hydrolysis of phthalyl peroxide with sodium hydroxide2 and by shaking phthalic anhydride with excess alkaline peroxide solution.2 The method described here is a modification of this latter process.3... 

The influence of temperature on the ortho effect has been evaluated in the alkaline hydrolysis in aqueous DMSO solutions of ortho-, meta- and para-substituted phenyl benzoates (26). The alcoholysis of phthalic anhydride (27) to monoalkyl phthalates (28) occurs through an A-2 mechanism via rate-determining attack of the alcohol on a carbonyl carbon of the anhydride (Scheme 4). Evidence adduced for this proposal included highly negative A 5 values and a p value of 4-2.1. In the same study, titanium tetra-n-butoxide and tri-n-butyltin ethanoxide were shown to act as effective catalysts of the half-ester formation from (27), the mechanism involving alkoxy ligand exchange at the metal as an initial step. ... 

A racemic alcohol may be converted into a racemic acid by reaction with one molar equivalent of phthalic anhydride the product is a half ester of a dicarboxylic acid (see Section 7.9.1). This can now be subjected to the resolution process for acids and, in due course, the alcohols can be regenerated by hydrolysis of the ester. 

Requests for larger samples for field testing necessitated the examination of alternate routes to AC 94,377. One of these started with 1-amino-1-cyclohexanecarboxamide and 3-chloro-phthalic anhydride. Attempted cyclization of the intermediate phthalamic acid 4 with cold trifluoroacetic anhydride gave, albeit in low yield, the readily isolated imidazoisoindole Biological evaluation of indicated that it had very similar PGR properties to that of AC 94,377 yet was perhaps slower acting. This was attributed to the slow hydrolysis of back to AC 94,377. 

Anhydrides. The corresponding acids, resulting from hydrolysis, are the most likely impurities. Distillation from phosphorus pentoxide, followed by fractional distillation, is usually satisfactory. With high boiling or solid anhydrides, another method involves refluxing for 0.5-1 hour with acetic anhydride, followed by fractional distillation. Acetic acid distils first, then acetic anhydride and finally the desired anhydride. Where the anhydride is a solid, removal of acetic acid and acetic anhydride at atmospheric pressure is followed by heating under vacuum. The solid anhydride is then either crystallised as for acid chlorides or (in some cases) sublimed in a vacuum. A preliminary purification when large quantities of acid are present in a solid anhydride (such as phthalic anhydride) can sometimes be... 

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. 

Friedel-Crafts). (A., 291, 9 C. r., 119, 139.)—When the dichloride of phthalic anhydride reacts with the hydrocarbon, benzene, in presence of anhydrous aluminium chloride, phthalophenone (diphenylphthalide) is formed (see p. 107). With phthalic anhydride itself the reaction can be made to take the same or a different course. Using an excess of hydrocarbon, condensation and hydrolysis occur, and o-benzoyl-benzoic acid or its homologues are obtained according to the reacting hydrocarbon. Not only can the latter be varied, but derivatives of phthalic anhydride may be used, so that a great number of compounds can be synthesised in this way. 

Breslow and coworkers420 have studied the hydrolysis of the anhydrides (128) and (129) in both the presence and absence of zinc(II) (and other metal ions). In the the absence of metal ion, hydrolysis of the anhydrides is independent of pH in the region 1.0-7.5, as also occurs with phthalic anhydride.421 However, in the presence of zinc(II), the hydrolysis is first order in hydroxide above pH 5. Table 28 lists values of kobs for the various substrates at pH 7.5 (for the metal complex k0bs = kOH[0H-]). The catalytic effects are of the order of 103. The pH dependence of the zinc(II) catalysis is consistent with attack by external hydroxide on a complex such as (130) where the metal acts as a Lewis acid catalyst. A further possibility involves attack by coordinated hydroxide on an uncoordinated anhydride carbonyl (131), and there is some evidence that this is indeed the process which does occur. 

The synthesis of amitriptyline starts from the key intermediate dibenzo-suberone (manufactured from phthalic anhydride) and can proceed by two pathways (Fig. 1). Treatment of dibenzosuberone with cyclopropyl Grignard gives the tertiary alcohol after hydrolysis. Reaction of the alco-... 

The reaction of azirine (42a) with phthalic anhydride does not lead to the oxazole,67 Rather, the ketoamide (138) is produced, presumably through hydrolysis of intermediate 137. 

More commonly, but incorrectly, named thiophthalic anhydride and sometimes referred to as phthaloyl monosulfide or o-phthalyl sulfide, this compound (104) may be prepared by heating phthalic anhydride with sodium sulfide125 or by heating phthaloyl chloride with potassium hydrogen sulfide,126 hydrogen sulfide,127 or ethanolic sodium disulfide.128 The reaction between phthaloyl chloride and hydrogen sulfide also gives phthalic anhydride and di-o-phthaloyl disulfide.127 Early attempts to prepare 104 have been described by Chakravarti.126 4-Nitrophthalic thioanhydride may be prepared by hydrolysis of 8 (R = N02 X = C1) (Section III, A).22... 

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