5 - , decarboxylation isolation

A special application of the Japp-Klingemann/Eischer sequence is in the preparation of tryptamines from piperidone-3-carboxylate salts, a method which was originally developed by Abramovitch and Shapiro[2]. When the piperidone is subjected to Japp-Klingemann coupling under mildly alkaline conditions decarboxylation occurs and a 3-hydrazonopiperidin-2-one is isolated. Fischer cyclization then gives 1-oxotetrahydro-p-carbolines which can be hydrolysed and decarboxylated to afford the desired tryptamine. 

Oxo 2 propylheptanoic acid (not isolated decarboxylates under conditions of its formation)... 

The a-acetobutyrolactone, with or without isolation, can be used in the preparation of various 5-substituted 2-butanone derivatives, presumably by decarboxylation of the acetoacetic acid obtained by ring hydrolysis. Simple hydrolysis gives 5-hydroxybutan-2-one (158) and acidolysis with hydrochloric acid gives 5-chlorobutan-2-one in good yields (159). 

Itaconic 2Lcid[97-65-4] (methylenebutanedioic acid, methylenesuccinic acid) is a crystaUine, high, melting acid (mp = 167-168) produced commercially by fermentation of carbohydrates (1 4). Itaconic acid is produced in the broth from citric acid (qv). Isolated from the pyrolysis products of citric acid in 1836, this a-substituted acryUc acid received its name by rearrangement of aconitic, the acid from which it is formed by decarboxylation. 

Practically all pyridazine-carboxylic and -polycarboxylic acids undergo decarboxylation when heated above 200 °C. As the corresponding products are usually isolated in high yields, decarboxylation is frequently used as the best synthetic route for many pyridazine and pyridazinone derivatives. For example, pyridazine-3-carboxylic acid eliminates carbon dioxide when heated at reduced pressure to give pyridazine in almost quantitative yield, but pyridazine is obtained in poor yield from pyridazine-4-carboxylic acid. Decarboxylation is usually carried out in acid solution, or by heating dry silver salts, while organic bases such as aniline, dimethylaniline and quinoline are used as catalysts for monodecarboxylation of pyridazine-4,5-dicarboxylic acids. 

The following synthesis of p ewdopelletierine is of special interest, since it involves only materials and conditions which could occur in plants and is therefore a possible bio-synthesis. Menzies and Robinson showed that when calcium acetonedicarboxylate, glutardialdehyde and methyl-amine are mixed in aqueous solution under specified conditions and the mixture is kept for twenty-four hours, a produet (XX) is formed, which can be decarboxylated to -pelletierine (XXI) and the latter isolated as the picrate, whieh after recrystallisation yields the pure base (m.p. 48-5°), the identity of which can be established by eonversion to the characteristic dipiperonylidene derivative. The course of the synthesis is represented as follows — ... 

A better yield was obtained when, in place of acetone, calcium acetonedicarboxylate was used, the initial product in this case being calcium tropinonedicarboxylate, from which the free dibasic acid is readily isolated and can be decarboxylated by heating in acid solution, yielding tropinone. This idea was taken up in Germany, and a number of processes for the production of tropinone derivatives have been described, mostly in patent literature. According to Willstatter and Pfannenstiel, a yield of... 

After isolation, the Michael adduct may be subjected to ester hydrolysis and decarboxylation. When a,p-unsaturated ketones are carried through this sequence, the final products are 5-keto acids (8-keto acids). 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

In a study of the nitrosation of camphor-3-glyoxylic acid (89), Chorley and Lapworth isolated a compound whose structure (90) has recently been clarified by Hatfield and Huntsman. Decarboxylation and ring expansion occur and the reaction is rationalized in the sequence 89 90. The buttressing effect of a methyl group on... 

Only in the case of the pyruvic acid condensation product was it possible to isolate the corresponding ethyl ester under these conditions. This, on mild hydrolysis, reverted to 1-methyl-1,2,3,4-tetrahydro-j8-carbohne-1-carboxylic acid, identical with the starting material, which therefore had the assigned structure 26 (R = CH3) and was not the SchiflF s base 25 (R = CH3). Alkaline hydrolysis of the ester was accompanied by decarboxylation. ... 

The decarboxylated 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-l-piperazinyl)-7-pyrido[l,2,3- /e]-l,4-benzoxazine-7-one was isolated from 5 injection (96MI16), and from boiling HCl solution of 5 (97MI18) and... 

The reasonable mechanism outlined above has not yet been rigorously proven in every detail, but is supported by the fact that a 1 1-intermediate 5 has been isolated." The ester groups are essential for the Weiss reaction because of the /3-keto ester functionalities however, the ester groups can be easily removed from the final product by ester hydrolysis and subsequent decarboxylation. 

The Hunsdiecker reaction is the treatment of the dry silver salt of a carboxylic acid with bromine in carbon tetrachloride. Decarboxylation occurs, and the product isolated is the corresponding organic bromide 16). Since dry silver salts are tedious to prepare, a modification of the reaction discovered by Cristol and Firth (77) is now... 

This ester (70 g) and diethyl carbonate (250 mg) were stirred at 90°C to 100°C while a solution of sodium ethoxide [from sodium (7.8 g) and ethanol (1 54 ml)] was added over 1 hr. During addition, ethanol was allowed to distill and after addition distillation was continued until the column heat temperature reached 124°C. After cooling the solution to 90°C, dimethyl sulfate (33 ml) was followed by a further 85 ml of diethyl carbonate. This solution was stirred and refluxed for 1 hr and then, when Ice cool, was diluted with water and acetic acid (10 ml). The malonate was isolated in ether and fractionally distilled to yield a fraction boiling at 148°C to 153°C/0.075 mm, identified as the alpha-methyl malonate. This was hydrolyzed by refluxing for 1 hr at 2.5N sodium hydroxide (350 ml) and alcohol (175 ml), excess alcohol was distilled and the residual suspension of sodium salt was acidified with hydrochloric acid to give a precipitate of the alpha-methyl malonic acid. This was decarboxylated by heating at 180°C to 200°Cfor 30 minutes and recrystallized from petroleum ether (BP 80°C to 100°C) to give 2-(2-fluoro-4-biphenylyl)propionic acid, MP 110°C to 111°C. 

For preparative purposes fermenting baker s yeast (Saccharomyces cerevisiae) is commonly used instead of a purified enzyme preparation. However, isolated pyruvate decarboxylates can also be used30. In this context, the most important substrate is benzaldehyde31 which is converted by n-glucosc fermenting yeast to (7 )-l-hydroxy-l-phenyl-2-propanone. This conversion has gained considerable industrial importance because ( )-l-hydroxy-1-phenyl-2-propanonc is an important precursor for the synthesis of (-)-cphedrin. 

Attempts to isolate the postulated substituted p-coumaric acid by hydrolysis have been of no avail, probably partly because of the known proneness of coumaric acid to decarboxylation followed by polymerization (3). In addition, evidence is available that the couma-royl residue is firmly attached to the as yet unexplored moiety of M. 

The use of microwave irradiation for decarboxylation reactions is well appreciated [107-110]. Still, only one example of a decarboxylation performed on 2-pyridone starting materials has been reported (Fig. 10) [111]. Notably, this decarboxylation reaction is a selective and reagent-free method performed in N-methyl-2-pyrrohdin one (NMP) and microwave irradiation at 220 °C for 10 min. The products 65 were isolated in excellent yields (92-99%) by a simple aqueous work-up (Fig. 10). 

Despite its synthetic importance, the mechanism of the copper-quinoline method has been studied very little, but it has been shown that the actual catalyst is cuprous ion. In fact, the reaction proceeds much faster if the acid is heated in quinoline with cuprous oxide instead of copper, provided that atmospheric oxygen is rigorously excluded. A mechanism has been suggested in which it is the cuprous salt of the acid that actually undergoes the decarboxylation. It has been shown that cuprous salts of aromatic acids are easily decarboxylated by heating in quinoline and that arylcopper compounds are intermediates that can be isolated in some cases. Metallic silver has been used in place of copper, with higher yields. ... 

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