Phthalamic acids

Phthalic anhydride (60 g. or 0.41 mole) is added gradually with stirring to 90 ml. of warm aqueous ammonia solution (sp. gr. 0.88). The anhydride dissolves with evolution of heat, and ammonium phthalamate separates from the solution. Cooling precipitates 70 g. (94%) of the ammonium salt. 

A solution of 30 g. (0.165 mole) of ammonium phthalamate in 30 ml. of cold water is treated with 20 ml. of concentrated hydrochloric acid. The solid formed is collected by filtration, and the white paste obtained is washed with cold water until free of chloride. The yield is 22 g. (81%). The phthalamic acid melts at 149° with loss of water, resolidifies at about 155°, and remelts at 231°. This represents conversion of phthalamic acid to phthalimide (m.p. 231°). 

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Derivatives with 3-nitrophthalic anhydride. 3-Nitrophthalic anhydride reacts with primary and secondary amines to yield nitro-phthalamic acids it does not react with tertiary amines. The phthalamic acid derived from a primary amine undergoes dehydration when heated to 145° to give a neutral A -substituted 3-nitrophthalimide. The phthalamic acid from a secondary amine is stable to heat and is, of course, soluble in alkali. The reagent therefore provides a method for distinguishing and separating a mixture of primary and secondary amines. 

The effect of the conformation of amic acid on the imidi2ation rate is also consistent with the observation that the thermal cycli2ation of model compounds, N-substituted phthalamic acids, is strongly influenced by the steric effect imposed by N-substituents (18). 

Many sigmoid rate curves have been reported. A typical example is provided by the hydrolysis of phthalamic acid. ... 

Phtal-. phthal-, phthalo-, phthalic. -amid-saure,-aminsaure,/. phthalamic acid, -azin,... 

A mino-2,4,6-tri iodo-N-methyl iso-phthalamic acid lothalmate meglumine... 

Phosphoryl chloride [10025-87-3], 4 Phthalamic acid, A V-diethyl-, methyl ester [2659344-2],63 Piperidine [110-894], 86, 118 acetate [4540-334], 118 Piperidine, 1 chloro- [2156-71-0], 118 Potassium cyanide [151-50-8], 20... 

Phthalamic acid N N diethyl-, methyl ester [Benzoic acid, 2 (/V, JV-diethyl aminocarbonyl)-, methyl ester), 63 Phthalicacid [1,2 Benzenedicarboxyhc acid], 86... 

Photosynthetic(II) chloroplasts, 2,773 Photosystem II dioxygen evolving centre manganese, 6, 586 manganese protein, 6, 590 Photothermography, 6, 118 Phthalamic acid, /V-(2-phenanthrolyl)-hydrolysis... 

For an example, see 10-9.) When this happens internally, we have an example of a neighboring-group mechanism at a carbonyl carbon. For example, the hydrolysis of phthalamic acid (77) takes place as follows ... 

Capon et al., 1978. No reference bimolecular reaction is available, but o-cyanobenzoic acid is hydrolysed over 10 times faster than phthalamic acid (A.3.9), although benzonitrile is less reactive than benzamide towards acid hydrolysis. [Rate constants for hydrolysis are (1-2) x 10 s for benzonitrile in 1 M acid (Hyland and O Connor, 1973) and 3.5 x 10-4 dm3 mol-1 s 1 for benzamide (Bender et al., 1958), both measured at 100°]... 

The pH-rate constant profile for hydrolysis of phthalamic acid showed participation by the undissociated carboxyl group, and an anhydride intermediate was detected (Bender, 1957 Bender et al., 1958b). Hydrolysis was 10 times faster than in the case of p-carboxybenzamide. A four-center mechanism [58] was postulated. 

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. 

Divalent metal ions inhibit the hydrolysis of N-(2-pyridyl)phthalamic acid (60) and N-(2-phenanthrolyl)phthalaxnic acid (61). In the case of (61) the substrate hydrolyzes by a pathway involving intramolecular general acid catalysis, and this pathway is inhibited by metal ions. Deprotonated amide complexes may also be involved leading to catalytically inactive complexes. 

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