Lead carboxylates synthesis

This imidazoline-carboxylate synthesis involves the coupling of four separate cont5)onents (two imines, an acid chloride and carbon monoxide), and the generation of at least five separate bonds, all via a one-pot, palladium catalyzed process. From an analysis of the structure of the imidazoline carboxylate, the individual constituents can be seen (Figure 3). This stmcture might be considered to arise from the dipolar cycloaddition of an imine with a mesoionic l,3-oxazolium-5-oxide (5) intermediate, which itself could be generated from imine, acid chloride and carbon monoxide. Consistent with this potential formulation, performing the catalytic reaction with CO leads to the incorporation of the carbon-13 label into the carboxylate position of 4. 

A further example is given below illustrating the use of a dibasic anhydride (succinic anhydride) the succinoylation reaction is a valuable one since it leads to aroyl carboxylic acids and ultimately to polynuclear hydrocarbons. This general scheme of synthesis of substituted hydrocarbons through the use of succinic anhydride is sometimes called the Haworth reaction. Thus a-tetralone (see below) may be reduced by the Clemmensen method to tetralin (tetrahydronaphthalene) and the latter converted into naphthalene either catal3d.ically or by means of sulphur or selenium (compare Section, VI,33). 

The N-to-C assembly of the peptide chain is unfavorable for the chemical synthesis of peptides on solid supports. This strategy can be dismissed already for the single reason that repeated activation of the carboxyl ends on the growing peptide chain would lead to a much higher percentage of racemization. Several other more practical disadvantages also tend to disfavor this approach, and acid activation on the polymer support is usually only used in one-step fragment condensations (p. 241). 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Resorcinol carboxylation with carbon dioxide leads to a mixture of 2,4-dihydroxyben2oic acid [89-86-1] (26) and 2,6-dihydroxyben2oic acid [303-07-1] (27) (116). The condensation of resorcinol with chloroform under basic conditions, in the presence of cyclodextrins, leads exclusively to 2,4-dihydroxyben2aldehyde [95-01-2] (28) (117). Finally, the synthesis of l,3-bis(2-hydroxyethoxy)ben2ene [102-40-9] (29) has been described with ethylene glycol carbonate in basic medium (118), in the presence of phosphines (119). Ethylene oxide, instead of ethyl glycol carbonate, can also be used (120). 

The reaction of 2-(a-pyridyl)alkylmalonic acid with J -piperideine leading to formation of 3-((x-pyridyl)quinolizidine-l-carboxylic acid on decarboxylation, has been used by Van Tamelen and Foltz (316) for the syntheis of the alkaloid lupanine (Scheme 20). A very elegant synthesis of matrine has been accomplished by Bohlmann et al. (317). 

In the endoplasmic reticulum of eukaryotic cells, the oxidation of the terminal carbon of a normal fatty acid—a process termed ch-oxidation—can lead to the synthesis of small amounts of dicarboxylic acids (Figure 24.27). Cytochrome P-450, a monooxygenase enzyme that requires NADPH as a coenzyme and uses O, as a substrate, places a hydroxyl group at the terminal carbon. Subsequent oxidation to a carboxyl group produces a dicarboxylic acid. Either end can form an ester linkage to CoA and be subjected to /3-oxidation, producing a... 

The structure of this compound is confirmed by the preparation of the 1-acetyl derivative, acid degradation to 4-methylquinoxalin-3-one-2-carboxylic acid (12), and alternative synthesis from the acid chloride of (12) and AW -dimethyluread A most unusual cyclization occurs when AW-dimethyl-o-phenylenediamine (15) is treated with alloxan in ethanolic solution this apparently involves an A-methyl group and leads to the formation of the spirobarbituric acid (16). The struc-... 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

Conversion of the carboxylic acid to the diethyl amide interestingly leads to an agent that exhibits the properties of a respiratory stimulant. One synthesis of this agent starts with the preparation of the mixed anhydride of nicotinic and benzene-sulfonic acid (4). An exchange reaction between the anhydride and diethyl benzenesulfonamide affords nikethemide (5). ... 

Carboxylic acid, 161, also serves as starting material for a substituted pyrazine that has proven to be an important diuretic agent. As the first step in the synthesis the acid is converted to the corresponding amide (165). Treatment with a single equivalent of hypobromous acid effects Hoffmann rearrangement of only one of the amide groups. Ethanolysis of the intermediate carbamate leads directly to the amino ester (166). Exposure of the... 

Spirapril (37) is a clinically active antihypertensive agent closely related structurally and mechanistically to enalapril. Various syntheses are reported with the synthesis of the substituted proline portion being the key to the methods. This is prepared fkim l-carbobenzyloxy-4-oxopro-line methyl ester (33) by reaction with ethanedithiol and catalytic tosic acid. The product (34) is deprotected with 20% HBr to methyl l,4-dithia-7-azospiro[4.4 nonane-8-carboxylate (35), Condensation of this with N-carbobenzyloxy-L-alanyl-N-hydroxysuccinate leads to the dipeptide ester which is deblocked to 36 by hydrolysis with NaOH and then treatment with 20% HBr. The conclusion of the synthesis of spirapril (37) follows with the standard reductive alkylation [11]. 

TheNef reaction of primary nitro compounds gives iildehydes or carboxylic acids, depending on the reaction conditions. Each transformation provides an important tool in organic synthesis. Primary nitro compotmds are converted into carboxylic acids vrith concentrated mineriil acids. Because such harsh conditions iilso lead to side reactions, a milder method is required inorganic synthesis. Basic phosphate-buffered KMnO rapidly converts primary nitroalkanes into carboxylic acids in 90-99% yield fEq. 6.13. "... 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

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