7-Dicarboxylic acids

The axially chiral dicarboxylic acid 27b was also uniquely reactive in achieving the highly enantioselective addition of aldehyde N,N-diaIkylhydrazones, a readily 

The structures of some common dicarboxylic acids and their pA a values are listed in Table 16.3. 

Although the two carboxyl groups of a dicarboxylic acid are identical, the two pATg values are different because the protons are lost one at a time and therefore leave from different species—namely, the first proton is lost from a neutral molecule, then the second proton is lost from a negatively charged ion. 

A COOH group withdraws electrons (compared to an H) and therefore increases the acidity of the first COOH group (Section 2.7). The values of the dicarboxylic acids show that the acid-strengthening effect of the COOH group decreases as the separation between the two carboxyl groups increases. 

Dicarboxylic acids readily lose water when heated, if they can form a cyclic anhydride with a five- or a six-membered ring. 

Cyclic anhydrides are more easily prepared if the dicarboxylic acid is heated in the presence of acetyl chloride or acetic anhydride. 

A structurally rather dissimilar pTyr mimic was developed by the Boehringer Ingelheim group, namely a triazole-dicarboxylic acid derivative 31 [130], which was shown to yield highly active Lck SH2 domain antagonists. 

Separate ionization constants, designated and K2, respectively, characterize the two successive ionization steps of a dicarboxylic acid. 

Oxalic acid Malonic acid Heptanedioic acid 

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Oxalic acid is poisonous and occurs naturaiiy in a number of plants including sorrei and begonia. It is a good idea to keep houseplants out of the reach of small children, who might be tempted to eat the leaves or berries. 

The examples of oxalic and malonic acids are atypical and are considered separately. Other dicarboxylic acids react essentially as alkanes (p. 297). 

Early work of Dhar established that oxidation of oxalic acid by chromic acid occurs readily, but some of his kinetic data are unreliable as the substrate itself acted as the source of hydrogen ions. The reaction is first-order in oxidant and is subject to strong manganous ion catalysis (as opposed to the customary retardation), the catalysed reaction being zero-order in chromic acid. This observation is related to those found in the manganous-ion catalysed oxidations of several organic compounds discussed at the end of this section. 

Chandra et al and also Bakore and Jain determined the rate law for the uncatalysed reaction to be 

A third set of results, those of Durham , indicates two paths, viz. 

Of the various results, these appear to the reviewer to be the most meticulously obtained and they do not fit the other two rate laws suggested. At 25 °C n =. 0M perchlorate), = 5.10x10 l mole. sec and = 4.78x10 l .mole . sec . The corresponding reaction intermediates are a neutral chelate mono-oxalato complex and a (non-chelate) bis-oxalato complex of Cr(VI). 

Self-associative lateral interactions can only occur with the AB-type analytes, chromatographed in sufficiently mild chromatographic conditions. In planar chromatography, this type of lateral interaction was first demonstrated on monocarboxylic fatty acids and a,co-dicarboxylic acids, chromatographed on microcrystalhne cellulose with aid of decalin and 1,4-dioxane as monocomponent eluents, respectively [8,20,23]. 

FIGURE 2.6 Concentration profiles of (a) hexadecanoic acid, sample concentration C = 0.025 mol 1 , (b) dodecanoic acid, sample concentration C = 0.1 mol 1 , obtained on microcrystalline cellulose with decaline as mobile phase [20]. 

FIGURE 2.7 Schematic representation of the self-association of dicarboxylic acids as a result 

FIGURE 2.9 Mixed linear/cyclic dimers of phenyl-substituted monocarboxylic acids (coupled together through the carboxyl groups and the aromatic 7t-electrons). 

FIGURE 2.10 Concentration profiles of 3-phenylpropionic acid obtained on microcrystalline cellulose with decalin as mobile phase. Sample concentrations were (a) 0.2, (b) 0.3, (c) 0.4, and (d) 0.5 mol-L [25]. 

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V,32. CYCI.OBUTANE-1 1-DICARBOXYLIC ACID AND CYCLOBUTANECARBOXYLIC ACID... 

Trimethylene dibromide (1 mol) condenses with ethyl malonate (1 mol) in the presence of sodium ethoxide (2 mols) to form ethyl cydobutane-1 1-dksrboxylate (I). Upon hydrolysis of the latter with alcoholic potassium hydroxide, followed by acidification cyciobutane-1 1-dicarboxylic acid (II) is obtained. 

When cyciobutane 1 1 dicarboxylic acid is heated above its melting point until the evolution of carbon dioxide ceases, cycZobutanecarboxyllc acid (III) is formed in good yield ... 

The procedure (with ethylene dibromide replacing trimethyleiie dibromide) described for cycZobutanecarboxylic acid (previous Section) does not give satisfactory results when applied to the cyclopropane analogue the yield of the cyclopropane-1 1 dicarboxylic acid is considerably lower and, furthermore, the decarboxylation of the latter gives a considerable proportion (about 30 per cent.) of butyrolactone ... 

Section 19.17 1,1-Dicarboxylic acids (malonic acids) and p-keto acids undergo thennal decar boxylation by a mechanism in which a p-caibonyl group assists the departure of carbon dioxide. 

Place 30 g. of cyclobutane-1 1-dicarboxylic acid in a 100 ml. distilling flask, fitted with a thermometer, and connect the side arm to a 60 ml. Claisen flask supported in a funnel so that it can be cooled externally by running water. Heat the distilling flask in a metal bath at 160-170°... 

A number of examples involving the stereochemistry of five membered rings are met in furanose sugars. An interesting example is that of 2, 5 dimethylcyclopentane 1, 1 dicarboxylic acid. This acid can exist in two geometrically isomeric forms which can be distinguished by decarboxylation. The cis xxvii isomer forms two monocarboxylic acids which are meso because they possess a vertical plane of symmetry. The trans isomer xxviii forms only one monocarboxylic acid and since it possesses no elements of symmetry, therefore, exists in optically active forms and a meso variety. 

B. 3-Cyclopentene-1 -carboxylic acid. A 250-mL, one-necked, round-bottomed flask is charged with 35.8 g of 3-cyclopentene-1,1-dicarboxylic acid and then fitted with a reflux condenser capped with a rubber septum and connected to a Nujol-filled bubbler by means of a syringe needle. The contents of the flask are heated in an oil bath at 170-175°C until carbon dioxide evolution is complete (ca. 2 hr) and then allowed to cool to room temperature. The resulting oil is transferred to a 50-mL flask and vacuum distilled without fractionation to provide 23.0 g (89% or 82% overall from dimethyl malonate) of 3-cyclopentene-1-carboxylic acid as a clear, colorless oil, bp 88°C (2 mm) (Note 7). 

It is noteworthy that in the synthesis of 117, the smaller Ugi macrocycle 118 was also formed. The lack of sterically demanding isopropyl groups in comparison to 113 allows the formation of this somewhat strained macrocycle. Because of this intriguing result, the diacid component in this reaction was varied to cyclopropane-1,1-dicarboxylic acid (Scheme 24) and tereph-thalic acid (Scheme 25). 

Phase-transfer conditions are used in the synthesis of cyclobutane-1,1-dicarboxylic acid (13). The pivotal step in this procedure is the initial ring formation to give the intermediate diethyl cyclobutane-1,1-dicarboxylate, which then undergoes subsequent acidic saponification to afford 13. albeit in a meager 23% yield.23 24... 

Decarboxylation reactions of cyclobutanecarboxylic acids appear to pose no particular problems. Cyclobutane-1,1-dicarboxylic acids can usually be decarboxylated thermally at temperatures up to 200 C.1 5> n 340 For example, cyclobutane-1,1,3,3-tetracarboxylic acid was heated to 185 °C at reduced pressure to give a mixture of cis- and frani-cyclobutane-l,3-dicarboxylic acid (l).1 Noteworthy in this reaction is the stereocontrof obtained in the product due to the formation of the anhydride. Generally, decarboxylation will give a mixture of cis- and transacids. The decarboxylation has sometimes been performed in a distillation step.4,5... 

Mercury(II) oxide together with a halogen is an early development of the classic Hunsdiecker reaction (bromodecarboxylation of a carboxylic acid silver salt, see below) which is still in use.20 22 A double Hunsdiecker reaction of cyclobutane-1,1-dicarboxylic acid with red mer-cury(ll) oxide in the presence of bromine gave 1,1-dibromocyclobutane (2) in 46% yield.21 However, a similar reaction performed on spiro[3.3]heptane-2-carboxylic acid afforded 2-bro-mospiro[3.3]heptane (3) in only 16% yield.22... 

A magnetically stirred mixture of cyclobutane-1,1-dicarboxylic acid (1.6 g, 11.1 mmol), HgO (3.3 g, 15.7 mmol), and Br2 (1.14 mL, 3.55 g, 22.2 mmol) in CH2C12 (40 mL) was heated at reflux for 80 min, cooled in an ice bath, treated with pentane (15 mL), and suction filtered. Following rinsing of the filter cake with pentane, the filtrate was concentrated by simple distillation. Pentane was added, the solids were removed by filtration, and the filtrate was washed with 1 M NaOH and brine prior to drying. The pentane was distilled to leave a residue, which in turn was bulb-to-bulb distilled to give the product yield 1.1 g (46%) bp 80-120 "C (bath)/31 Torr. 

Carbonation and subsequent hydrolysis of either lithiated or sodiated metallocenes lead to the corresponding carboxylic acids. Ferrocenecarboxylic acid and ferrocene-1,1 -dicarboxylic acid are readily produced in this manner and can be conveniently separated by extraction of the former with ethyl ether or benzene. The reaction of metalated ferrocenes with various chlorosilanes has led to a variety of triaryl- or trialkvlsilylferrocenes (3, 28, 90). 

Cyclopentane-1,1-dicarboxylic acid [5802-65-3] M 158.1, m 184. Recrystd from water. 

Cyclopropane-1,1-dicarboxylic acid [598-10-7] M 130.1, m 140 . Recrystd from CHCI3. 

Reactions of alkane-1,1-dicarboxylic acids, e.g. la, alkane-1,4-dicarboxylic acids, e.g. lb, and their longer-chain homologs with sulfur tetrafluoride afford mixtures of bis(trifluoromethyl)-alkanes, bis(pentafluoroalkyl) ethers and small amounts of polyethers.118 Total yields, generally, decrease with increasing length of the carbon chain and in the presence of C = C bonds. 

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