Phthalide, reaction

A general route to l,3-diaryl-benzo[c]thiophenes starts with the synthesis of an aryl-substituted phthalide, reaction of this with an aryl (heteroaryl) Grignard reagent, then thionation using Lawesson s reagent. ... 

According to this new reaction network, the starting material is converted to the wanted product PA by three parallel routes via phthalic aldehyde and phthalic acid (reactions 8,9,10), via tolylic acid and phthalide (reactions 5,6,7) and via phthalide (reactions 4 and 7). Phthalic anhydride when formed is very stable but it is converted in part via bencoic acid (reaction 26) over a rather complex reaction scheme to maleic anhydride (MA). Maleic anhydride is formed directly from o-xylene via tolylic aldehyde (reaction 1) and toluene (reaction 11) by two routes and via dimethylben-zochinone (DMBQ) (reaction 15). Toluene and DMBQ are converted over a series of reaction steps to acetic acid. The main by-products, CO and CO2, are predominantly formed directly from o-xylene according to this mechanistic study. 

The isocoumarin 151 is prepared by the intramolecular reaction of 2-(2-propenyDbenzoic acid (149) with one equivalent of PdCbjMeCN) . However, the (Z)-phthalide 150 is obtained from the same acid with a catalytic amount of PdjOAc) under 1 atm of Oi in DMSO, alone is remarkably efficient in reoxidizing Pd(0) in DMSO. The isocoumarin 151 is obtained by the reaction of 2-(l-propenyl)benzoic acid (152) under the same conditions[4], 2-Vinylbenzoic acid (153) is also converted into the isocoumarin 154, but not to the five-membered lactone) 167,170],... 

Condensation of an appropriately substituted phenylacetic acid with phthalic anhydride in the presence of sodium acetate leads to aldol-like reaction of the methylene group on the acid with the carbonyl on the anhydride. Dehydration followed by decarboxylation of the intermediate affords the methylenephthal-ides (12). Treatment of the phthalides with base affords directly the indandiones, probably via an intermediate formally derived from the keto-acid anion (13). The first agent of this class to be introduced was phenindandione (14) this was followed by anisindandione (1S) and chlorindandione (16). ... 

Preparation of the key intermediate to this series begins by reduction of the methylene phthalide, 12a, with hydriodic acid and red phosphorus. Cyclization of the acid (26) thus obtained affords the tricyclic ketone, 27. Reaction with the Grignard reagent from 3-dimethylamino-2-methylpropyl chloride affords the... 

To a hot solution of 20.6 g of sodium in 400 ml of absolute ethanol, there is added a solution of 110 g of phthalide and 110 g of p-methoxybenzaldehyde. A vigorous reaction ensues and one-helf of the alcohol is distilled off over a two hour period. Ice and water are added to the red solution end the diluted solution is ecidified with hydrochloric acid. The resulting gum solidifies end the aqueous phase is removed by decantation. The crude solid is recrystallized twice from two liters of ethenol yielding 2-(p-methoxyphenyl)-1,3-indandione as pale yellow crystals, MP155°-156°C. 

There is a considerable presumption that steric twisting from coplanarity, which diminishes effective transmittal of pi-electron effects, has appreciable effect on X. For example, the X = 1.10 for the phthalide saponification rate (no. 28 of Table III) compared with X=. 89 for the corresponding benzoate saponification rate is probably a reflection of the rigid coplanarity conditions imposed in the former structure. However, the reactions were carried out in differing compositions of H2 0-Et0H solvent, so that a solvent effect may also be involved. 

Reaction of 2-formylbenzoic acids with 1, 1-bisdialkylaminoethylenes in acetic anhydride has been found91 to yield phthalides such as 21. These color formers are claimed to yield blue to green images, but have also been described92 as intermediates for the preparation of divinyl phthalides by a route identical to that described in Scheme 3, for which they are probably of more significance. (See Section 4.6.2.)... 

Finally, bisindolylethylenes have also been reacted with tetrahaloph-thalic anhydrides to yield color formers showing absorption in the near infrared.99 The chief advantage over the diarylethylenes is the availability of the starting materials. The bisindolylethylenes may be prepared in situ by reaction of an indole with acetyl chloride and then converted directly to the phthalide without isolation. 

The reaction of the keto acids (66) with 4-alkoxydiphenylamines (75 R = CH3, C2H5) is widely used to prepare fluoran compounds developing green or black colors. The reaction in concentrated sulfuric acid gives intermediate phthalide compounds (76), which are then treated with base to convert into 2 -anilino-6 -aminofluorans (77) (Eq. 5). 

It is essential that the temperature of the first step not exceed 35 °C to minimize undesirable decomposition of the 4-alkoxydiphenylamines. In addition, the 4-alkoxydiphenylamines should be added to a solution of the keto acids in sulfuric acid. The reverse order of addition does not produce good results, because the 4-alkoxydiphenylamines are liable to decompose in sulfuric acid even at lower temperature. On the other hand, the phthalides are stable to a considerable extent in sulfuric acid at 35°C or below. The reaction is substantially completed in a few hours after dissolution of the 4-alkoxydiphenylamines. The second step proceeds easily at 50 °C or higher, and sodium hydroxide is successfully employed as base, though any base can be used. 

The reaction of the keto acids with 4-hydroxydiphenylamines (75 R = H) gives directly the fluoran compounds (77), not via phthalide intermediate. The yields, however, are much lower than those using 4-alkox ydiphen ylamines. 

A wide variety of M W-assisted aldol [59, 60] and Knoevenagel condensation reactions have been accomplished using relatively benign reagents such as ammonium acetate [61], including the Gabriel synthesis of phthalides with potassium acetate [62],... 

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 first examples of a homogeneous reduction of this type were reported in 1971. Cobalt carbonyl was found to reduce anhydrides such as acetic anhydride, succinic anhydride and propionic anhydride to mixtures of aldehydes and acids. However, scant experimental details were recorded [94]. In 1975, Lyons reported that [Ru(PPh3)3Cl2] catalyzes the reduction of succinic and phthalic anhydrides to the lactones y-bulyrolaclone and phthalide, respectively [95], The proposed reaction sequence for phthalic anhydride is shown in Scheme 15.15. Conversion of phthalic anhydride was complete in 21 h at 90 °C, but yielded an equal mixture of the lactone, phthalide (TON = 100 TOF 5) and o-phthalic acid, which is presumably formed by hydrolysis of the anhydride by water during lactoniza-tion. Neither acid or lactone were further hydrogenated to any extent using this catalyst system, under these conditions. 

The Elsevier system has since been shown to carry out several ester hydrogenations that were previously deemed impossible [114]. The hydrogenation of dimethyl phfhalate to phfhalide with ruthenium cluster catalysts has already been discussed (Table 15.15, Entry 4). The application of [Ru(acac)3] and triphos -this time with a 20-fold excess of Et3N as additive - delivers good yields of phthalide. However, the use of isopropanol (I PA) as solvent and 24% HBF4 allows further hydrogenation to 1,2,-bis-hydroxylmethyl benzene for the first time. Both of these reactions were carried out under milder conditions (100°C, 85 bar H2, 16 h) than those reported previously. 

In contrast to the above benzonitriles, 2-methylbenzonitrile (11.88) did undergo cyano hydrolysis, but by a very indirect route involving cytochrome P450 catalyzed hydroxylation of the 2-Me group to form 2-(hydroxyme-thyl)benzonitrile (11.89), followed by intramolecular nucleophilic addition. The cyclization reaction yielded an unstable imino ether derivative (11.90), which hydrolyzes to phthalide (11.91). The conversion of 2-(hydroxyme-thyl)benzonitrile to phthalide followed first-order kinetics with a f1/2 value of 2.8 h at pH 7.4 and 37° [124],... 

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. 

Reaction of the carbonium ion with water could be reduced if overlap occurred with the carboxylate anion of aspartic acid-52 either during or after the glycoside-cleavage step. Since the carboxylate anion would be held adjacent to the carbonium ion in the active site, equilibrium should be far to the side of the acylal. Reaction of acylal with H2O would then very probably be ratedetermining in the forward direction. Evidence has been obtained that the solvent is directly involved in the hydrolysis of the cyclic acylal 2-(p-nitrophenoxy)phthalide where steric factors are similar... 

By analogy, benzocyclopropene (1) is formed in low yield via biradical cycliza-tion upon irradiation of benzocyclobutenone (79), upon its flash vacuum pyrolysis, or upon pyrolysis of indan-2,3-dione (80). Reaction of phthalide 81 in a RF plasma leads also to However, these latter extrusion methods are of no preparative interest. 

Other approaches to alkylidenecycloproparenes have been attempted without success. Aromatization of appropriate alkylidenecyclopropanes or their precursors could not be realized, and flash vacuum pyrolysis of methylene phthalide and 3-methylene-2-coumaranone afforded rearrangement products rather than alkylidenecycloproparenes via extrusion of 002. The photochemical or thermal decomposition of the sodium salt of benzocyclobutenone p-toluenesulfonyl hydrazone led to products derived from dimerization of the intermediate benzocy-clobutenylidene, or from its reaction with the solvent, but no ring-contracted products were observed. When the adduct of methylene-l,6-methano[10]annulene to dicyanoacetylene (249) was subjected to Alder-Rickert cleavage, phenylacety-lene (250) was formed, which derives reasonably from the parent 234. ... 

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