4-Aminocyclohexane-carboxylic acid

Ferber and Bruckner reduced />-aminobenzoic acid using Adams catalyst (Pt02) at atmospheric pressure, and Schneider and Dillman reduced p-aminobenzoic acid using 10% rhodium on carbon at 140 atm. and 70°. 3-Isoquinuclidone has been prepared, by the previously mentioned investigators, by heating the dry 4-aminocyclohexane carboxylic acid at elevated temperatures. 

The described method of preparation of 3-isoquinuclidone has the following advantages The isolation of the cis form of 4-aminocyclohexane carboxylic acid is not required in order to obtain a good yield the amount of 3-isoquinuclidone that can be prepared at a time is limited only by the size of available equipment the yield is excellent and the workup is easy and straightforward. 

Table 3 Isomerization of ds-4-aminocyclohexane carboxylic acid on Raney nickel catalyst (Metalyst). Effect of the amount of catalyst, temperature and H2 pressure...

In addition cts-isomer of 4-aminocyclohexane carboxylic acid isolated by fractional ciystallization from the reaction mixture obtained in the Parr reactor was also reacted over Raney nickel catalyst to prepare the desired trans-isomer with high yield. It is... 

The H-NMR spectrum of pure as-4-aminocyclohexane carboxylic acid ethyl ester is seen in Figure 1. Signals with chemical shift at 5=1.2-1.3 ppm can be assigned to the protons of the methyl group, whereas the signals of the -CH2- protons... 

Figure 1 NMR spectrum of as-4-aminocyclohexane carboxylic acid ethyl ester.

The H-NMR spectrum of lra/3s-4-aminocyclohexane carboxylic acid ethyl ester is enriched in a mixture containing ca. 10 % of the cis isomer is seen in Figure 3. The signals belonging to the protons next to the ester and amino groups in the trans isomer appeared at chemical shifts of 5=2.20 ppm and 5=2.65 ppm, respectively. The intensity of signals in the NMR spectra allows estimating the ratio of stereoisomers. 

In conclusion, 4-Amino-benzoicacid can be hydrogenated to 4-aminocyclohexane carboxylic acid on 5wt.% Ru- and Rh/A Os catalysts with 100% yield in 2 wt. % Na0H-H20 at 80-100 °C, 10 MPa H2, for 5h. However, the ratio of trans/cis stereoisomers of the product does not exceed a value of 1/1. Raw reaction mixture... 

In a detailed H NMR study (employing also Pr(N03)3 and Eu(fod)3 as shift reagents), Palaima et al. (97MI74) estimated the stereoconfigurations and conformational equilibria of the cis/trans isomers of 3- and 4-aminocyclohexane carboxylic acid the cis/trans ratios of the isomeric mixtures were determined. 

C. Intramolecular Cyclization of 4-Aminocyclohexane-carboxylic acid Derivatives... 

Larsson, O. M., Johnston, G. A. R., and Schousboe, A. (1983) Differences in uptake kinetics of cis-3-aminocyclohexane carboxylic acid into neurons and astrocytes in primary cultures. 

Aminocyclohexane carboxylic acid Model Cyclic /1-chain Amorin et al. (2003)... 

Perhaps the most common synthetic route to aminocyclohexane carboxylic acids is reduction of nitro- and amino-substituted benzoic acid derivatives. Reduction of (9rt/io-substituted acids give 7.706 reduction of meM-substituted acids give 7.104-, and reduction of pzira-substituted acids give 7.57102... 

Derivatives of mono- and dicarboxylic acids are another important source of ortho- and mefa-aminocyclohexane carboxylic acids, but not the para-derivatives. Anhydride 7.181 was converted to the amide, then to 7.777 (c/s-2-aminocyclohex-ane-1-carboxylic acid) via a Hofmann reaction,12 and finally to cis- ethyl 2-amino-... 

The 1,3-dipolar cycloaddition reaction of nitrones has been used in a short synthesis of 4-hydroxyproline, and in an asymmetric synthesis of the proline analogue (190) from a protected mannose oxime. Baldwin and his co-workers have reported a total synthesis of another heterocyclic amino-acid, the antitumour agent AT-125 (191). Syntheses of pipecolic acid and its analogues (192), aminopiperidinecarboxylic acids related to nipecotic acid (193), and c/5-3-aminocyclohexane carboxylic acid (194) have also been published. 

The effect of C ,C -disubstituted amino acids (aaAAs) on peptide secondary structure has been studied in recent years.2a d While longer side-chain C ,C -di-n-alkyl amino acids promote extended peptide conformation,23 alicyclic aaAAs, in which the Ca carbon forms a cyclic bridge with itself, such a 1-aminocyclopentane-l-carboxylic acid (Ac5c) and 1-aminocyclohexane-l-carboxylic acid (Ac6c), have helix-forming characteristics similar to those of 1 -aminoisobutyric acid (Aib).2ax... 

A-Phthaloyl-ctx-l-aminocyclohexane-4-carboxylic acid tert-butyl perester (LUGCUL) 1.459 132.0 172... 

The interaction of l-phenyl-4-aminocyclohexane 1-carboxylic acid (14) with PC15 is accompanied by cyclization and formation of the imidochloride (15). Alcoholysis of the latter resulted in the lactim ether (16).44... 

To 1-aminocyclohexane-l-carboxylic acid (350 mmol) dissolved in 1.25 L of methyl alcohol in a glass reactor was added 51 ml thionyl chloride in portions at —5°C. The mixture was stirred 5 hours then stood overnight. Thereafter, the mixture was concentrated, the residue mixed with water, the solution pH adjusted to 9 using Na2C03, and extracted twice with CH2CI2. The organic phase was dried, re-concentrated, and the product isolated in 66% yield. 

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