Phthalic decarboxylation

It was first described in 1608 when it was sublimed out of gum benzoin. It also occurs in many other natural resins. Benzoic acid is manufactured by the air oxidation of toluene in the liquid phase at 150°C and 4-6 atm. in the presence of a cobalt catalyst by the partial decarboxylation of phthalic anhydride in either the liquid or vapour phase in the presence of water by the hydrolysis of benzotrichloride (from the chlorination of toluene) in the presence of zinc chloride at 100°C. 

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). ... 

As pointed out previously, controlled degradation reactions are very difficult with aliphatic or alicyclic hydrocarbons, and most of the relabeling work has been concentrated on aromatic reaction products. Procedures have been extensively described by Pines and co-workers (e.g., 97, 96, also 87, 89-98, 95, 98). For the present purpose, it suffices to note that the 14C contents of the methyl side-chains and the rings in aromatic reaction products are readily estimated by oxidation of the methyl to carboxyl, followed by decarboxylation, while ethyl side-chains may be oxidatively degraded one carbon atom at a time. Radiochemical assays may be made on CO2 either directly in a gas counter, or after conversion to barium carbonate, while other solid degradation intermediates (e.g., benzoic acid or the phthalic acids) may be either assayed directly as solids or burned to CO2. Liquids are best assayed after burning to CO2. 

Formerly, benzoic acid was produced by the decarboxylation of phthalic anhydride. Oxidation of acetophenon, benzyl bromide, and toluene with sulfur and water has been described in the literature, but are not commercially feasible routes of synthesis. Carboxylation of benzene with carbon dioxide is not practical due to the instability of benzoic acid at the required reaction conditions [8]. 

Benzoic acid [65-85-0], C6H5COOH, the simplest member of the aromatic carboxylic acid family, was first described in 1618 by a French physician, but it was not until 1832 that its structure was determined by Wnfiler and Liebig. In the nineteenth century benzoic acid was used extensively as a medicinal substance and was prepared from gum benzoin. Benzoic acid was first produced synthetically by the hydrolysis of benzotrichloride. Various other processes such as the nitric acid oxidation of toluene were used until the 1930s when the decarboxylation of phthalic acid became the dominant commercial process. During World War II in Germany the batchwise liquid-phase air oxidation of toluene became an important process. 

Attempted anodic bis-decarboxylation of o-phthalic acid (as its dianion) failed to give any evidence for benzyne formation 174h... 

Trimellitic anhydride yielded products derived both from benzyne and carboxybenzyne. Decarboxylation at 690° should be extensive, and this compound then would react like phthalic anhydride. Under the circumstances, the survival of appreciable amounts of carboxybenzyne derivatives was surprising. The 4-methyl ester of trimellitic anhydride would probably be a stable source of carboxybenzyne methyl ester. 

Using this methodology, iodocubanes are prepared by decarboxylative iodination in presence of 2,2,2-trifluoroiodoethane595. ortho-Bromobenzoic acid derivatives are prepared from phthalic acids (equation 69)596. 

Shihunine, C12H13O2N (mp 79° picrate, mp 163°-164°) (I) was obtained from Dendrobium lohohense Tang et Wang (4) its phthalide-pyrrolidine structure was established by reduction and decarboxylation to 1-methyl-2-phenylpyrrolidine, by oxidation to phthalic acid, and with the help of IR-spectral data. 

Derivation (1) Decarboxylation of phthalic anhydride in the presence of catalysts (2) chlorination of toluene to yield benzotrichloride, which is hydrolyzed to benzoic acid (3) oxidation of toluene (4) from benzoin resin. 

The low value of the raw materials compared to the premium price paid for chloride-free benzaldehyde and benzoic acid makes the commercial utilization of the process attractive despite the difficulties involved. The production of benzoic acid by the direct oxidation of toluene lias not reached the proportions that benzaldehyde has. lthough the production of beuzoic acid directly is feasible with the correct catalysts, small quantities only from this source are being marketed and are obtained as a by-product of the catalytic oxidation of toluene to benzaldehyde. Because of the difficulty in the selection of correct catalysts, the oxidation oi toluene to benzoic acid is complicated by the oxidation going too far with resultant loss of raw material or by the formation of gummy condensation products intermixed with the benzaldehyde, benzoic acid, maleic acid and anthra-quinone. These complications have deterred commercial application of the oxidation process in the face of the newer process for forming benzoic acid by the decarboxylation of phthalic anhydride. 

A number of vapor phase processes employing decarboxylating or carbon dioxide splitting catalysts have been proposed. In these processes the mixture of steam and phthalic anhydride vapor is circulated over the catalysts in a chamber maintained at temperatures varying from 300° to 450° C., depending on the active materials employed. 

When naphthalene is degraded by permanganate under precisely defined conditions, phthalonic acid can be isolated instead of the usual phthalic acid, and this intermediate can be decarboxylated to phthalaldehydic acid (see page 1007) 150... 

The product acid decarboxylates to CO and the phthalic anhydride path should produce half the quantity of CO2 of isotopic mass 47 ( C 0 0) that the direct path yields. Knowing the isotopic composition of reactants the proportion of the reaction flux through each path is calculable from the ratio of 47 to 44 masses and the result is that only the anhydride path is taken. 

Considerable benzoic acid is manufactured by the decarboxylation of phthalic acid, a process that yields a chlorine-free product. The development of this decarboxylation process has served to restrict the investigation of air-oxidation methods. 

Oxidative decarboxylation of acids to alkenes is often accompanied by alkene rearrangement. Lukas J. Goossen of the Max-Planck-lnstitut, Muhlheim, has found (Chem. Commun. 2004, 724) that in situ activation of the acid with phthalic anhydride and inclusion of the bis phosphine DPE-Phos substantially slow alkene isomerization, which can be essentially eliminated by running the reaction to only 80% conversion. Both linear and branched carboxylic acids work well. 

Application of this technique to the identification of methyl esters of the organic acids obtained by the controlled oxidation of bituminous coal allowed the more volatile benzene carboxylic acid esters to be identified (Studier et al., 1978). These were esters of benzene tetracarboxylic acid, tere-phthalic acid, toluic acid, and benzoic acid. Decarboxylation of the total acid mixture was shown to afford benzene, toluene, Cj-benzenes (i.e., ethylbenzene or xylenes), Cj-benzenes, butylbenzenes, Cj-benzenes, Cybenzenes, naphthalene, methylnaphthalene, C2-naphthalene, biphenyl, methylbi-phenyl, C3-biphenyl, indane, methylindane, Cj-indane, phenanthrene, and fluorene. 

The production of benzoic acid from naphthalene, practised up to the end of World War II, is possible in one stage, without the isolation of the intermediate phthalic acid. Oxidation of naphthalene is carried out at 340 °C with zinc oxide. This decarboxylates the phthalic acid in the gas-phase however, conversion in this reaction is not complete, and the benzoic add must be separated from the phthalic acid. Separation is possible by dissolving the phthalic acid in water. 

Decarboxylation of phthalic acid in the liquid-phase also leads to the production of benzoic acid. In this process, developed by Monsanto, liquid phthalic anhydride is converted over nickel oxide or copper oxide with the introduction of steam at 220 °C. 

Malonate anions are convenient sources of ester enolates. They react with halides and a variety of other electrophiles. Acid hydrolysis of the ester followed by decarboxylation gives the mono-acid. An example of this approach used phthalic anhydride 1.178) as a starting material in a reaction with 2-aminoethanol to give 1.179. Conversion of the alcohol moiety in 1.179 to its 0-benzenesulfonate ester... 

Another common use of amino acids first converts them to an amino aldehyde derivative, which can then undergo a variety of reactions. The phthalimido derivative of glycine (1224, prepared from the reaction of glycine and phthalic anhydride) was condensed with diethyl 2-fluorosuccinate. This product was hydrolyzed (and it proceeded with decarboxylation) to give 2-fluoro-4-phthalimidobut-2-enoic acid, 1225, but in very poor yield. 32 Despite the poor conversion, this is a simple and fast route to these compounds. 

Figure 3.6) from Escherichia coli after the incorporation of U-[ C]-(—)-shikimic acid gave phthalic acid (28) which retained 90 per cent of the total radioactivity of the original quinone . Decarboxylation of (28) using the Schmidt procedure gave carbon dioxide which contained 7 per cent of the total activity. Similar results were obtained by Guerin, Leduc and Azerad with the menaquinones of Mycobacterium phlei and in work with a Bacillus megaterium mutant, Zenk and Floss and their collaborators ... 

Evidence to support this proposal has been obtained by Burnett and Thomson in work with the madder plant (Rubia tinctorum). 2-[ C]-Mevalonic acid was administered to this plant and was incorporated into a series of anthraquinone metabolites such as alizarin (101), purpurin (124) and pseudopurpurin (102). Degradation of the quinones to phthalic acid showed that all the radioactivity was confined to ring C. Decarboxylation of pseudopurpurin (102) gave purpurin (124) containing one half of the total radioactivity and this is in agreement with the hypothesis outlined above namely that ring C of these quinones is derived by cyclisation of a precursor such as lapachol (122). Burnett and Thomson s observations imply that the two methyl groups in the precursor (122)... 

---