Phthalides, formation

Sakamoto, M. (1998) Solid-State Photochemistry of o-Aroylbenzothioates Absolute Asymmetric Phthalide Formation Involving 1,4-Aryl Migration, J. Am. Chem. Soc., 49, 12770-12776. 

Scheme 25 Mechanism for the phthalide formation via aryl migration.

Scheme 26 Absolute asymmetric phthalide formation via radical pair intermediate.

Protection of alcohols. This reagent is suitable for acylation of the hydroxyl group at C-2 of glycosyl donors. Esters are formed by conventional manipulation and their clearage is triggered by phthalide formation... 

Retrosynthetically, virgatolide B (2) would be derived from aldol 26 following spiroketalization and phthalide formation via dihydroxylation/carbonyla-tion (Scheme 9). Importantly, the order in which the spiroketal and phthalide structures are constmcted remained flexible in this strategy, enabling late stage adaptation if necessary. Aldol 26 would be constmcted using the Mukaiyama aldol reaction employed for aldol 8, while methyl ketone 27 would be assembled via Suzuki coupling of trifluoroboratoamide... 

Chiral thietane-fused (3-lactam from an achiral monothioimide using the chiral crystal environment. /. Am. Chem. Soc., Vol. 115, p. 818 (b) Takahashi, M. Sekine, N. Fujita, T. Watanabe, S. Yamaguchi, K. Sakamoto, M. (1998). Solid-state photochemistry of o-aroylbenzothioates Absolute asymmetric phthalide formation involving 1,4-aryl migration. /. Am. Chem. Soc., Vol. 49, pp. 12770-12776... 

Another approach to improve the color formation properties of Malachite Green lactone has been the introduction of nitrogen atoms into the phthalide ring. Thus, condensation of pyridine-2,3-dicarboxylic acid anhydride with dimethylaniline in the presence of zinc chloride has been shown54 to yield a mixture of the 4- and 7-azaphthalides 11 and 12. 

Fusion of the two arylamino groups of a triarylmethane phthalide color former results in the formation of spirofluorene phthalides. Due to the increased planarity of this system, a bathochromic shift results leading also to color formers showing infrared absorption when developed. This was first exemplified in 1983102 by preparation of phthalide 26 as shown in Scheme... 

One further example of this principle of bridging the aryl groups of a triarylmethane phthalide was reported in 1986.108 Thus, treatment of phthalide 27 with aluminum chloride results in the formation of the spirobenzanthracene 28 as shown in Scheme 11. These color formers also exhibit absorption in the near infrared spectral region, but no further reports of such compounds have since been published. 

Chapter 4 is concerned with a technically important group of leuco compounds which like the spiropyrans are not formed by reduction of the parent dye, but by formation of a spiro structure from the dye in such a way that the newly created sp3 center destroys the conjugation, and hence, the color of the chromophore. These are the phthalides (spirolactones) and the position of equilibrium is determined by pH rather than a redox process. Such materials are used mainly as color formers in pressure-sensitive... 

The principles needed to design a polymer of low flammability are reasonably well understood and have been systematized by Van Krevelen (5). A number of methods have been found for modifying the structure of an inherently flammable polymer to make it respond better to conventional flame retardant systems. For example, extensive work by Pearce et al. at Polytechnic (38, 39) has demonstrated that incorporation of certain ring systems such as phthalide or fluorenone structures into a polymer can greatly increase char and thus flame resistance. Pearce, et al. also showed that increased char formation from polystyrene could be achieved by the introduction of chloromethyl groups on the aromatic rings, along with the addition of antimony oxide or zinc oxide to provide a latent Friedel-Crafts catalyst. 

Benzo[c]furans (isobenzofurans) are reactive molecules usually employed as reactive dienes in the synthesis of more complex molecules. In the synthesis of spiro compounds related to fredericamycin A, Kumar generated the trimethylsiloxytrimethylsilylbenzo[c]furan 125 from phthalide via two consecutive deprotonations and silylations of the resulting anions. Diels-Alder reaction of the isobenzofuran as shown below with a spiroenedione leads to the formation of an endo-exo mixtures that can be smoothly converted to the dihydroxydione <00IJC(B)738>. 

The choice of catalyst controls the intramolecular cyclisation of 2-(l-alkynyl)benzoic acids, with AgNCh effecting efficient formation of 3-substituted isocoumarins, but Ag powder favouring a 5-exo-dig-cyclisation to the phthalide (Scheme 45) <00T2533>. 

The gas-phase reaction of N2O5 and naphthalene in an environmental chamber at room temperature resulted in the formation of 1- and 2-nitronaphthalene with approximate yields of 18 and 7.5%, respectively (Pitts et ah, 1985). The reaction of naphthalene with NOx to form nitronaphthalene was reported to occur in urban air from St. Louis, MO (Randahl et ah, 1982). The gas-phase reaction of naphthalene with OH radicals yielded phthalaldehyde, phthalic anhydride, phthalide, 1,4-naphthoquione, cis- and rra/J5-2-formylcinnamaldehyde, and 2,3-epoxy-1,4-naphthoquinone. 

The gas-phase selective oxidation of o-xylene to phthalic anhydride is performed industrially over vanadia-titania-based catalysts ("7-5). The process operates in the temperature range 620-670 K with 60-70 g/Nm of xylene in air and 0.15 to 0.6 sec. contact times. It allows near 80 % yield in phthalic anhydride. The main by-products are maleic anhydride, that is recovered with yields near 4 %, and carbon oxides. Minor by-products are o-tolualdehyde, o-toluic acid, phthalide, benzoic acid, toluene, benzene, citraconic anhydride. The kinetics and the mechanism of this reaction have been theobjectof a number of studies ( 2-7). Reaction schemes have been proposed for the selective pathways, but much less is known about by-product formation. 

The coupling of 2-iodobenzoic acid and phenylacetylene under Sonogashira coupling conditions was found to give a mixture of an isocoumarin derivative and a phthalide (4.40.), The proper choice of the catalyst system led to the preferential formation of the latter compound.53 The process might also be diverted towards the formation of the isocoumarin derivative by isolation of the intermediate o-cthynyl-benzoic acid and its subjection to carefully selected cyclization conditions54... 

Another route to anthraquinones has been devised which relies on the addition of carbanions (22) derived from phthalides to arynes (81JCS(P1)2120). For the formation of anthraquinone (23) itself, phthalide was treated with 2.2 equivalents of lithium diisopropyl-amide in THF. Bromobenzene was then added and the reaction mixture warmed to room... 

The diesters (625), prepared from ethyl 2-chloromethylbenzoate, are cyclized by sodium ethoxide in a classical Dieckmann reaction (71BSF1351). When R = Me, the formation of phthalide was observed, which was thought to arise by attack of the ethoxide at the methyl group with loss of ethyl acrylate (Scheme 243). 

Results of a kinetic study of the formation of phthalide by dehydrobromination of a-bromo-o-toluic acid are believed to provide support for an intimate ion-pair mechanism for the pyrolysis of some types of halo acids in the gas phase.51... 

Addition of an ethereal solution of prop-2-ynylmagnesium bromide to phthalides 1 at 0°C followed by quenching of the reaction mixture with 20% HC1 results in direct formation of the benzoxepinones 2 in 45-86% yield. 

Electrochemical reduction of phthaloyl dichloride (73) at a carbon or mercury cathode in acetonitrile containing TEAP led to a complex array of products. Six cathodic waves observed in the CV for the reduction of phthaloyl dichloride arise from the reductions of different electrolysis products, as well as from hydrolytically formed phthalic anhydride (74),. caused by the presence of residual water in the solvent/supporting electrolyte (equation 45). From controlled potential electrolyses of phthaloyl dichloride, a variety of products including 3-chlorophthalide (75), phthalide (76), biphthalyl (77) and dihydrobiph-thalide (78) can be obtained69,70. Reduction of glutaryl dichloride (79) at a mercury cathode in acetonitrile containing 0.1M TEAP results in the formation of 5-chlorovalerolactone (80) and valerolactone (81) as minor products, and a polymeric material (equation 46)68. 

However, the ketone VI/63 did not undergo transamidation reaction either under acidic or under basic conditions5 When the primary amino function in VI/63 was protected (as a phthalide by Nefkens reagent [49] [50]), the planned transformation of VI/64 to VI/1 via VI/66, VI/68, VI/69, outlined above and in Scheme VI/14, was realized in an overall yield of 56 % [10]. The behavior of the ketone VI/63 suggest an aminoacetal formation of type VI/73 [51]. Such a compound can be of interest for metallion transport phenomena in plants, because isomers of VI/63 are natural products and may have some functions in nature. A detailed analysis of this abnormal behavior is in progress [51]. 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

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