Amino phthalimides

In a similar manner to the formation of pyridazines from AT-aminopyrroles, cinnolines or phthalazines are obtainable from the corresponding 1-aminooxindoles or 2-amino-phthalimides. If the relatively inaccessible 1-aminooxindoles are treated with lead tetraacetate, mercuric acetate, r-butyl hypochlorite (69JCS(C)772) or other agents, cinnolones are formed as shown in Scheme 105. The reaction was postulated to proceed via an intermediate... 

The use of A-aminophthalimide as a nitrogen source in aziridination reactions has been examined. One of the problems associated with A-aminophthalimide as a nitrogen source is the need for a strong oxidant. The use of electrochemical catalysis with A-amino phthalimide has proved to be an effective and mild route for aziridination <05JOC932>. Both electron-rich and electron-poor substrates worked well in this reaction. 

Direct preparation of an aziridine from an alkene is possible by reaction of the alkene with a nitrene or metal nitrenoid species. Nitrenes can be generated thermally or photochemically from azides, although their reaction with alkenes to give aziridines is often low yielding and is complicated by side reactions. Oxidation of iV-amino-phthalimide or related hydrazine compounds (e.g. with Pb(OAc>4 or by electrolysis) and reaction with an alkene has found some generality. The metal-catalysed reaction of nitrenes with alkenes has received considerable study. A variety of metal catalysts can be used, with copper(II) salts being the most popular. For example, styrene was converted to its A-tosyl aziridine 72 by reaction with [A-(tosyl)imino]phenyliodinane (PhI=NTs) and copper(II) triflate (5.75). ... 

A major advance was accomplished with the introduction of hydrazine derivatives by Che, in particular, M-amino phthalimide [38]. Although initial work had relied on PhI(OAc)2 as the oxidant, the same group later discovered that a tricomponent system consisting of 2-iodoanisole (49), wCPBA, and the A -amino phthalimide could be employed for an in situ preparation of the required imino-iodane [39]. It is important to note that the final iminoiodane contains a 2-methoxyphenyl substituent, which is in line with the observation from Zhdankin on enhanced solubility of derivatives of the type 42. Under these conditions, a series of styrenes 48 could be submitted to intermolecular aziridination and provided products 50 under mild conditions and in good to excellent yields. 

An additional example comprises an intramolecular cyclization. The most notable is the transformation of the amide of W-amino phthalimide 134 which, upon treatment, with PIFA undergoes clean benzylic amination to the corresponding lactam derivatives 135 [79]. 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Phthalides — see Benzo[c]furan-l (3H)-one Phthalimide, 2-amino-pyridazine synthesis from, 3, 53 Phthalimide, N-cyclohexylthio-as vulcanization accelerator, 1, 404 Phthalimide. methylidine-polymerization, 1, 273 Phthalimide, N-(trichloromethylthio)-biocide, 1, 399 Phthalimide, 1-vinyl-polymerization, 1, 273 Phthalimide, N-vinyl-copolymer... 

Photolysis, apparatus for, 55, 17 Phthalimide, N-amino- [ 1//-Isoindole-1,3-(2//)-dione, 2-amino-, 55, 115 Potassium rew-butoxide [2-Propanol, 2-methyl-, potassium salt], 55,12, 13 Potassium iodide, 55, 71 Potassium permanganate [Permanganic acid, potassium salt], 55,68 Propane, 2,2 dimethyl 1 phenyl, 55, 112 Propane, 2 isocyano-2-methyl-, 55, 96... 

The modified procedure involves refluxing the N-substituted phthalimide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydtazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has beai employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

A similar sequence that takes place under milder conditions uses 4-nitrophthalimides as the protecting group and /V-melhylhydrazine for deprotection.234 Reduction by NaBH4 in aqueous ethanol is an alternative method for deprotection of phthalimides. This reaction involves formation of an o-hydroxybenzamide in the reduction step. Intramolecular displacement of the amino group follows.235... 

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). 

All these features were observed experimentally for solutions of 3-amino-/V-methylphthalimide, 4-amino-/V-methylphthalimide, and for nonsubstituted rhoda-mine. The results were observed for cooled, polar solutions of phthalimides, in which the orientational relaxation is delayed. Exactly the same spectral behavior was observed [50] by picosecond spectroscopy for low viscosity liquid solutions at room temperature, in which the orientational relaxation rate is much higher. All experimental data indicate that correlation functions of spectral shifts Av-l(t), which are used frequently for describing the Time Dependent Stokes Shift, are essentially the functions of excitation frequency. 

In a joint paper, Loupy and Gedye [45] reported an investigation of the influence of MW activation on the synthesis of phthalimides by the reaction of phthalic anhydride with several amino compounds (Scheme 4.20) both in the absence of solvent and in the presence of a nonpolar solvent. 

A useful approach for the preparation of chiral (3-aminophospho-nic acids from the naturally occurring a-amino acids has been reported.139 The overall scheme (Equation 3.4) involves formation of the phthalimide-acid halide from the starting a-amino acid followed by a Michaelis-Arbuzov reaction with triethyl phosphite to give the acylphosphonate. Complete reduction of the carbonyl group in three steps followed by hydrolysis of the ester and amide linkages provides the target material in very high yield without racemization (>99% ee). 

Yet another structural principle is represented by metal complex pigments based on isoindolinones. Condensation of amino-iminoisoindolinones (imino-phthalimide) with 2-aminobenzimidazole in a high boiling solvent affords an azomethine (36). This compound reacts with salts of divalent metals, such as Co, Cu, Ni, to yield yellow azomethine metal complex pigments [10] ... 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

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