Camphor carboxylic acid

Further evidence for the formation of intermediate compounds in catalytic reactions is afforded by the observation (a) that optically active camphor is formed from optically inactive (racemic) camphor carboxylic acid in the presence of the d- or /-forms of quinine, quinidine or nicotine and (6) that optically active bases, e.g., quinidine, catalyze the synthesis of optically active mandelonitrile from benzaldehyde and hydrocyanic acid.10 These results hardly admit of any other interpretation than the intermittent production of a catalyst-reactant compound. 

Calcium D-galactonate, I, 70 Calcium D-gluconate, III, 141, 142, 149, 152, 155, 156, 161 IV, 331 Calcium hypochlorite, III, 165 Calcium 2-keto-D-gIuconate, III, 148, 155 Calcium 5-keto-D-gluconate, III, 156 Calcium lactobionate, calcium bromide double salt, III, 155 Calcium Ievulinate, IV, 311 Calcium maltobionate, III, 161 Calcium D-mannonate, III, 152 Calcium pectate, I, 334 Calcium D-rhamnonate, III, 144 Calcium salts, in preparation of aldonic acids with NaCN, I, 23 Calcium vicianobionate, III, 154 Calcium D-xylonate, III, 155 Camphor, optically active, formed from inactive (racemic) camphor carboxylic acid in the presence of quinine, quinidine or nicotine, V, 53 Camphor carboxylic acid. See Camphor. Camphor, 3-hydroxy-, IV, 89 Camphorquinone, phytochemical reduction of, IV, 89... 

Several syntheses of chiral camphor derivatives make use of the CH acidity of the methylene group attached in a-position to the carbonyl function (C-3). Thus, isoamyl nitrite converts camphor to 3-isonitrosocamphor which readily undergoes hydrolysis to the yellow camphorquinone. Bromination leads to 3-bromocamphor which is sulfonated to 3-bromocamphor-3-sulfonic acid with concentrated sulfuric acid. 3-Lithiated camphor obtained with phenyllithium is carboxylated to endo- and exo-isomers of camphor carboxylic acid. The Claisen condensation of camphor with esters of carboxylic acids provides enolized chiral 1,3-diketones, converting metal cations to chiral metal chelates. 

Supplement 1950 1505-1591a acid, 269. Hydroxy-carbonyl sulphonic acids Camphor-sulphonio acid, 345. Carboxylic-sulphonic acids, 368. Se and Te acids, 422. 

Certain pairs of enantiomers, such as 25°C solutions of camphor in aqueous ethanol (Fig. 26a), 2,2,5,5-tetramethyl-l-pyrrolidinoxy-3-carboxylic acid in chloroform (Fig. 26b), or carvoxime in hexane (Fig. 26c), cocrystallize throughout the entire range of mole fractions. The crystals that are in equilibrium with the saturated liquid solution are solid solutions (mixed crystals), since they constitute a single phase. The racemic solid solution is termed a pseudoracemate [141]. 

Dimethylbiphenyl-2,2 -dicarboxylic acid, l,l -binaphthyl-2,2 -diyl hydrogen phosphate, camphor-10-sulfonic acid, acenocoumarol, proglumide, Af-succinyl-1-phenylethylamine, 3,4-dihydro-4-(2-naphthyl)-1,3,6-trimethyl pyrimidine-2(lH)-one-5-carboxylic acid... 

X-Ray diffraction studies of ( )-carbocamphenilone," of (-)-camphene-8-carboxylic acid," and of a number of Money s brominated camphor derivatives (Vol. 6, p. 39 Vol. 7, p. 40) have been published they include 8-bromo-camphor," l,7-dibromo-3,3,4-trimethylnorbornan-2-one, l,7-dibromo-4-... 

A camphor-based 3-acyl-2-oxazolidinone has also been used for diastereoselective alkylations66. The A-acylated auxiliary 18 is prepared in three steps from 7,7-dimethyl-2-oxobicy-clo[2.2.1]heptane-l-carboxylic acid (ketopinic acid, 17)67. Deprotonation by lithium diiso-propylamide in tetrahydrofuran at — 78 °C and subsequent alkylation with activated halides [(bromo- or (iodomethyl)benzene, 3-bromo- or 3-iodopropene] furnished moderate to good yields of alkylation products in high diastereomeric ratios (>97 3 by H NMR). With added hexamethylphosphoric triamide the alkylation yields are increased and bromoalkanes also give satisfactory yields. The diastereomeric ratios are, however, much lower (d.r. 70 30 to 85 15)67. 

Formation of a six-membered ring by cyclization of a,y-carboxylic acid groups is also observed in the reaction of sulfur tetrafluoride with (1 / , S)-( + )-camphoric acid besides 1,2,2-trimethyl-3-(trifluoromethyl)cyclopentanecarbonyl fluoride (20) and camphoroyl difluoride (21). the bicyclic tetrafluoro ether, 2,2,4,4-tetrafluoro-l,8,8-trimethyl-3-oxabicyclo[3.2.1]octane (22). is formed. The ratio of products strongly depends on the reaction conditions.250... 

Racemic piperazine-2-carboxylic acid (4-azapipecolic acid, 22) is obtained by hydrogenation of pyrazine carboxylic acid salts/236 For its enantiomeric resolution several methods have been described, e.g. fractional crystallization of its S-camphor-10-sulfonic add salt/236,237 fractional crystallization of l,4-dibenzylpiperazine-2-carboxylic add menthyl ester/238 or selective digestion of racemic piperazine-2-carboxylic add amide by leucine aminopeptidase/239 ... 

Other methods to form carboxylic acids Cyanotrimethylsilane, 87 a-Substituted carboxylic acids (see also Amino acids, Halo carbonyl compounds, Hydroxy acids) Camphor-10-sulfonic acid, 62 Chiral compounds Alcohols... 

Although a large number of chiral dienophiles have been developed (Table 26.2), their ability to provide high asymmetric induction appears to be limited to specific dienes. However, there are some dienophiles that tolerate a wider variety of dienes including menthol derivatives,117 118 camphor derivatives,6 39 40 105 107-113 181 182 and oxazolidinones.120 165 183 184 It should be noted that even these auxiliaries would require an efficient recycle protocol for economic scale up. One exception is the use of sacrificial chiral oxazolidinones, which are relatively inexpensive. This approach has been used in the large-scale preparation of the base cyclohexane unit of Ceralure Bj.168 A procedure has been developed for the preparation of (75,25)-5-norbomene-2-carboxylic acid where the D-panta-lactone auxiliary can be recycled efficiently.185186... 

It has also been found that certain aldehydes, ketones and carboxylic acids esters form well defined products with nitric acid (Reddelien [5]). For example, bemzaldehyde with 60% nitric acid gives a colourless, unstable oil, and cinnamic aldehyde forms fairly stable white crystals, melting at 60-61°C, with 65% nitric acid. Acetophenone, benzophenone, fluorenone, phenanthrenoquinone and camphor give similar addition products. 

An alternative method to the Baeyer-Villiger reaction is that of oxidation with formaldehyde oxide. The latter can be generated by treatment of vinyl acetate with ozone, which gives, beside the wanted products, the mixed anhydride of acetic and formic acid. If a ketone is added to the ozonide mixture, formaldehyde oxide can be trapped to yield the corresponding ozonide, which on thermal decomposition forms the lactone and (or) the corresponding olefinic carboxylic acid. The transformation of camphor (11/202) to the lactone 11/203 by this method has been achieved in 63% yield [131]. 

Asymmetric Hydrogenation of Camphor-Derived Sul-tamides. The sultamide of CSA can be used as a chiral auxiliary for synthesis of 3-substituted carboxylic acids (eq 20). ... 

Fig. 9.33. Chromatograms illustrating the spectrum of applicability of chiral anion exchangers derived from cinchonan derivatives (reprinted with permission from Ref. 1388]) (mobile phase McOH-O.l M ammonium acetate (80 20) pHj = 6.0 T = 25°C flow rate. I ml/min UV detection) (unless otherwise stated), (a) r7.v-3-Aminocyclopentanc carboxylic acid as DNZ derivative on CSP 1. (b) Heptelidic acid on CSP Vll T = I0°C. (c) 2-(rm-Butylsulphonylmethyl) 3-phcnyl propionic acid on CSP IX. (d) Camphor-10-sulphonic acid on CSP II. (e) 3-(3-Carboxy-pipcrazin-I-yl)propyIphosphonic acid as DNP-dcrivative mobile phase MeOH-0.5 M ammonium acetate (90 10) pH., = 6.0. (f) Omcpra/ole on CSP IX mobile phase. ACN-O. I M ammonium acetate (65 35) pH., = 5.0 T = 0"C. (g) 3,4-Dihydro-2H-pyran-2-carboxylic acid (reprinted with permis.sion from Ref. [73]) (for structure of CSPs see Fig. 9.32).

In this reaction the bond between the carbonyl-C-atom and the C-atom of the tertiary alcohol is cleaved oxidatively to yield the original starting material for this synthesis, camphor, and carboxylic acid 28. 

In order to determine the structure of the photochemical rearrangement product of carvone camphor in methanol, and to prove its structure, the research team of T. Gibson subjected the bicyclic carboxylic acid product to a degradation sequence, which commenced with the HVZ reaction, followed by dehydrohalogenation, dihydroxylation and glycol cleavage. 

Many organosulfur compounds can be resolved into optically active forms (enantiomers) owing to the presence of a chiral (asymmetric) sulfur atom 5 important examples include sulfoxides and sulfonium salts. Chiral sulfoxides containing amino or carboxylic acid groups have been resolved by formation of the diastereoisomeric salts with d-camphor-10-sulfonic acid or d-brucine. The salts can then be separated by fractional crystallisation and the free optically isomeric sulfoxides liberated by acid hydrolysis. However, a more convenient synthetic procedure for the preparation of chiral sulfoxides of high optical purity is Andersen s method (see p. 30). 

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