Amidation with phthalic anhydride

Aromatic nitriles are also prepared by heating amides with phosphorus pentoxide, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, and ammonium sulfamate. In addition, the action of a double salt of aluminum and sodium chlorides, NaCl- AlClj, gives excellent yields of nitriles from both aliphatic and aromatic amides. Heating an amide with phthalic anhydride causes dehydration. A novel synthesis consists in treating a mixture of an aromatic acid and p-toluene-sulfonamide with phosphorus pentachloride the yields of nitriles range from 63% to 79%. ... 

Hydrolysis of amides. Primary amides are hydrolyzed to carboxylic acids by heating in the dry state with phthalic anhydride at 240-250°. Thus, pivalamide affords pivalic acid in 91% yield (the side product is phthalimide). 

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. 

Considerable research effort has been devoted in recent years to the use of chloral derivatives for the synthesis of linear heterocyclic polymers. Of these, the most common are aromatic polyimides [1-12], Many of these polymers have been synthesised from compounds like 4,4 -diaminobenzophenone, and other diamines, which, as demonstrated in the previous chapter, can be obtained from chloral. Polyimides prepared from these diamines were largely synthesised by the conventional two-step procedure [11, 12] involving mild reaction of the diamines with the bis(phthalic)anhydrides, isolation of poly(o-carboxy)amide (PCA) prepolymers, and then processing into products followed by thermal or chemical imidisation [13—16] (Scheme 3.1). Some properties of polyimides prepared from 4,4 -diaminobenzophenone are provided in Table 3.1. 

Carboxylic acids react with aryl isocyanates, at elevated temperatures to yield anhydrides. The anhydrides subsequently evolve carbon dioxide to yield amines at elevated temperatures (70—72). The aromatic amines are further converted into amides by reaction with excess anhydride. Ortho diacids, such as phthalic acid [88-99-3], react with aryl isocyanates to yield the corresponding N-aryl phthalimides (73). Reactions with carboxylic acids are irreversible and commercially used to prepare polyamides and polyimides, two classes of high performance polymers for high temperature applications where chemical resistance is important. Base catalysis is recommended to reduce the formation of substituted urea by-products (74). 

The reaction of phthalic anhydride with 1,3,4,6-tetra-0-acetyl-2-amino-2-deoxy-D-glucose leads to the formation of the expected A-phthaloyl amide or phthalamic acid. Furthermore, intramolecular condensation occurs, presumably by way of a mixed anhydride intermediate, on treating this with ethyl chloroformate, thereby forming an A,A-phthaloyl imide, 1,3,4,6-tetra-0-acetyl-2-deoxy-2-phthalimido-D-glucose.105 106 The 2-amino-2-deoxy-D-glucose derivative can be regenerated by the action of hydrazine.69 107... 

The details of this synthesis will be explained under naphthalene (p. 766). The synthesis of anthranilic acid from ortho-i hthalic acid takes place according to the following reactions. Phthalic acid, or better phthalic anhydride, by treatment with ammonia yields phthal-amidic acid, which in turn yields phthalimide. 

The reaction is accomplished by simply heating together phthalic anhydride and ammonium carbonate. Phthalimide then hydrolyzes with potassium hydroxide yielding the potassium salt of phthalamidic acid and this acid amide compound undergoes the Hofmann reaction (pp. 148, 685) with bromine (or chlorine) and potassium hydroxide by which one of the carboxyl groups is replaced by the amino group yielding amino benzoic acid or anthranilic acid. 

Primary and secondary amides and thioamides react with alkyl chlorofoimates with loss of CO2 or COS, forming iminium chlorides (82 equation 52). In some cases this method is complementary to the Pinner imido ester hydrochloride synthesis. The iminium salt (83 Scheme 6) formed by action of ethyl chloroformate on DMF is labile and decomposes rapidly to ethyl chloride. If the reaction is performed in the presence of NaBp4, the iminium salt (85) is isolable. Aryl chlorofoimates react in the same fashion with DMF or DMA, but in these cases the aryloxymethyleneiminium compounds are fairly stable, so this reaction is an important method for the preparation of compounds of this type. - Succinic acid monoamides, phthalic acid monoamides and related compounds are cyclized to iminium salts (86 equation 53) by treatment with acetic anhydride and HC104. ° With the aid of trifluoromethanesulfonic anhydride lactams and amides can be converted to dication ether salts (87) and (88 Scheme 7).22i.222... 

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. 

The hydrolysis rate of phthalamic acid is 105 times faster than that of benzamide. Formation of a phthalic anhydride intermediate has been demonstrated in C13- and 018-labeling experiments (13). These results and the degradation data are consistent with the previously proposed mechanism of intramolecular displacement of the protonated amide moiety by the carboxylate anion (7,13,14). 

Detection of an intermediate by double labelling is well exemplified in the hydrolysis of phthalamic acid to phthalic acid [49]. One mechanism involves phthalic anhydride as an intermediate and this may be checked by labelling the amide carbon with C and the water with 0 (Eqn. 68). 

A large number of dibasic acids and anhydrides are used in the preparation of poly(ester amide)s. These include terephthalic acid, phthalic anhydride, isophthalic acid, endic endo-cis bicyclo(2,2,10-5)-heptene-2,3-dicarboxylic] anhydride, hydrogenated endic anhydride, maleic anhydride, fumaric acid, dichloromaleic anhydride, itaconic acid, brassylic acid, dimer acid, adipic acid, sebacic acid, succinic acid, trimeUitic anhydride, pyrromellitic anhydride and ethylenediamine tetraacetic acid (EDTA). However, tri- and poly-functional compounds are used only partially and are combined with bifunctional derivatives, or derivatives of previously prepared multifunctional compounds which are subsequently polymerised with bifunctional compounds. 

A few hyperbranched poly(ester amide)s have been prepared using a similar A2 + BBV approach, in which phthalic anhydride or maleic anhydride as an A2 monomer and diethanol amine as a BB 2 monomer were used. The polycondensation polymerisation technique is used to prepare the polymers. These poly(ester amide)s are modified by long alkyl chain (fatty acids) end groups. The dielectric properties of the modified polymers were investigated over a range of frequencies and temperatures. No relaxation peak was noticed in the dielectric spectrum at different temperatures. Castor oil and Mesua ferrea L. seed oil-based hyperbranched poly(ester amide)s are prepared using diethanol fatty amide of the oils with different types of anhydrides and dibasic acids with or without diethanolamine. 

Retention of ester groups. Equimolar amounts of startg. nitrile and tetrafluorophthalic acid heated at 135° for 4 days in a heavy-walled glass pressure tube product. Y 56%. Work-up is simple since no solvent is required. F.e.s. W.D. Rounds, G.W. Gribble, Tetrahedron Letters 29, 6557-60 (1988) from carboxylic acid amides with tetrachloro-or tetrafluoro-phthalic anhydride s. ibid. 6553-6. 

Phthaloyl chlorides [isophthaloyl chloride (ICL) and terephthaloyl chlo-ride(TCL)] are made by at least two processes, both involving the chlorination of phthalic acid. In the first (13), xylene is chlorinated by a photochemical reaction to form hexachloroxylene. The hexachloroxylene then reacts with phthalic acid to give the corresponding phthaloyl chloride and by-product HCl. Phthaloyl chloride is purified by double distillation. To produce ICL by this reaction, m-xylene and isophthalic acid are the starting materials. To produce TCL, the process starts with p-xylene and terephthalic acid. Phthaloyl chlorides can also be produced by reacting intermolecular anhydrides of the corresponding acids with phosgene, in the presence of an amide catalyst such as DMF or DMA (14). 

In this regard, the polycondensation of trimellitic anhydride chloride (4-chloro-carbonyl phthalic anhydride) with diamines at low temperature can be considered as a model reaction, and it has been the subject of numerous studies [190-192]. As usual, the first product formed in these reactions is poly(amide amic acid), which is eventually converted into poly(amide imide) by cyclodehydration. Some of these poly(amide imide)s from diamines and trimellitic anhydride have been reported as technical materials, and marketed as high Tg engineering thermoplastics [7]. 

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