Phthalimides, ring opening

Aminomethyl)biphenyl-2-carboxylic acid (70) and -acetic acid (69) have been prepared from dibenzo-substituted oxepin-2-one 66 by potassium phthalimide ring opening. Further Arndt-Eistert homologation of 67 provided 68.[104]... 

As an extension of this chemistry, the [3+2] cycloaddition reaction of new atropisomeric 4-dialkylamino-5-chloro-l,2-dithiole-3-thiones 130 and DMAD or its diethyl analogue has been utilized to give thioacid chlorides 131 (Scheme 13) <20030L929>. These have been converted into thioamides 132 with 2 equiv of pyrrolidine (or morpholine) by substitution of the 5-chloro substituent and phthalimide ring opening. Similar reactivity toward 1 or 2 equiv of pyrrolidine was noted for 130, which was obtained according to the general method described. 

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 second proposed mechanism involves initial ring opening of the phthalimide. Alkoxide attack on one of the imide carbonyls furnishes amide anion 26. Proton transfer affords enolate 27, which undergoes Diekmann type condensation followed by aromatization to afford the requisite isoquinoline 23. 

Finally the aminoquinoline bearing a primary amine at the terminal carbon atom of the side chain is itself an effective antimalarial drug. Ring opening of 2-methyltetrahydrofuran by bromine gives the dibromide, 99. The primary halide is sufficiently less hindered so that reaction with potassium phthalimide affords exclusively the product of displacement of that halogen (100). Alkylation of the aminoquinoline with lOO affords the secondary amine, 101. Removal of the phthalimide group by means of hydrazine yields primaquine (102). ... 

The Gabriel synthesis represents another indirect but highly valuable approach to amines. Trost has demonstrated a method for the asymmetric ring-opening of butadiene monoepoxide by use of one equivalent of phthalimide, 7t-allylpalladium chloride dimer, and the chiral bisphosphine 22 (Scheme 7.37). The dynamic kinetic asymmetric transformation proceeded through a putative achiral intermedi-... 

Photoinduced electron transfer from the carboxylate ion to the excited triplet phthalimide (fcT = 293-300 kj mol-1) appears to be followed by a rapid protonation of the radical anion and cyclization via a biradical recombination reaction (Scheme 9.1). Acetone (which also acts as photosensitizer) containing a small amount of water is the solvent of choice, whereas potassium carbonate is the ideal base to enhance cyclization versus simple decarboxylation and ring opening of the phthalimide [4]. 

The photochemical reaction of A -methylphthalimide with 1,1-diphenyl ethene affords the phthalimide adduct (329) and the ether (330) in 44 and 12 % yield respectively. With imide (331) the byproducts are the ring opened adduct (332) and the ether (330) in yields of 31 and 44% yield respectively. The authors suggest that the formation of the ether is the result of a second electron transfer as illustrated in Scheme 11. ... 

Alkynes can add to thiocarbonyl groups to afford stable thietes. A reaction typical of this behaviour is the addition of hex-3-yne or diphenylacetylene to the monothio phthalimide 121 to yield the thietes 122 . In some instances the resultant thietes are unstable and undergo ring opening to a thioester as with the addition of dithiomethoxyacetylene to the same phthalimide 121. The product from this reaction is the thioester 123 . Interestingly the dithiophthalimide is unreactive under these conditions. Additions of this type have also been reported for xanthenethione and thioxanthenethione. The formation of thioesters 124 occurs on irradiation of the thiones 125 with dithio-r-butoxyacetylene. The reaction involves the formation of an unstable thiete which ring opens to afford the final products. ... 

Intramolecular cyclization of (76) in the presence of NaH gave exo (77) and endo (78) products (Equation (9)) <90SL584). Allene-based electrophile-mediated cyclization afforded iV-tosyl iodohexa-hydroazocines <94JCS(Pl)3549>. Photochemical intramolecular cycloaddition of phthalimide in acetone afforded the ring-opened product <82TL498l>. An unstable enaminone azocine derivative (81) was formed after the desulfurization of the bicyclic aminal (80), which in turn was synthesized from... 

The key step in another synthesis is a Michaelis-Arbusov reaction of diethyl methylphosphonite with the JV-protected 2-amino-4-bromobutanoic acid. According to apaper from the Monsanto company [15], the latter may be obtained from bromobutyrolactone, which is first treated with phthalimide, and after ring-opening, esterified. [16]... 

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