1.2- diaminocyclohexane

Solubility soluble in aqueous acidic solution, alcohols, and most organic solvents. 

Form Supplied in colorless liquid both enantiomers are commercially available. 

Preparative Methods cheap and readily available racemic trans-1,2-diaminocyclohexane can be resolved with d-(—)-tartaric acid, giving (15, 25 )-diaminocyclohexane with 98% enantiomeric excess. Detailed procedures for the resolution have been published. Determination of enantiomeric excess is made by HPLC analysis of the A(Af -bis(m-toluyl) derivative on a Pirkle L-Leucine-DNB column. Direct separation of enantiomers by preparative HPLC on a chiral colunrn has also been described.  

Handling, Storage, and Precautions air- and C02-sensitive bottles should be stored under an inert gas atmosphere, preferably away from direct light. 1,2-Diaminocyclohexane is harmful by inhalation and contact with skin. May be fatal if swallowed. Incompatible with strong acids and strong oxidizing reagents. 

Chiral C2-symmetric vicinal diamines have emerged as powerful tools for the synthesis of enantiomerically pure compounds and are now commonly used as chiral auxiliaries or ligands for a wide array of asymmetric chemical transformations, with efficiencies comparable to those obtained with the closely related 

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Unequivocal syntheses of cis- and mns-(i -decahydroquinoxalincs have been achieved by lithium aluminum hydride reduction of the corresponding cis- and trans-decahydroquinoxaIin-2-ones. The latter compounds were prepared by condensation of chloroacetic acid and cis- and trans-1,2-diaminocyclohexane, respectively. The resolution of frans-dUdecahydroquinoxaline was effected by use of first dibenzoyl-cZ-tartaric acid and then of dibenzoyl- -tartaric acid. "" (C/. p. 215.)... 

Perez-Soler, R., Khokhar, A. R., Hacker, M. P., and Lopez-Berestein, G. (1986). Toxicity and antitumor activity of cis-bis-cyclopentenecarboxylato-1,2-diaminocyclohexane platinum(II) encapsulated in multilamellar vesicles. Cancer Res., 46. 6269-6273. 

By heating 2-benzyloxycyclohexanone 208 and (R)-l-phenylethylamine in refluxing toluene for 4 days in a Dean-Stark apparatus, the imine 209 was formed, then a rearrangement occurred to give first the a-aminocyclohexanone derivative 210 and finally the Q, o -disubstituted imine 211 with moderate diastereoselectivity. Reduction of this imine with sodium borohydride gave a mixture of two trans diamines (S,S)-212 and (R,R)-212, which were separated by chromatography. The enantiomers of 1-benzyl-1,2-diaminocyclohexanes 213 were then obtained by hydrogenolysis [99] (Scheme 31). 

The reductive amination of ketones can be carried out under hydrogen pressure in the presence of palladium catalysts. However, if enantiopure Q -aminoketones are used, partial racemization of the intermediate a-amino imine can occur, owing to the equilibration with the corresponding enam-ine [102]. Asymmetric hydrogenation of racemic 2-amidocyclohexanones 218 with Raney nickel in ethanol gave a mixture of cis and trans 1,2-diamino cyclohexane derivatives 219 in unequal amounts, presumably because the enamines are intermediates, but with excellent enantioselectivity. The two diastereomers were easily separated and converted to the mono-protected cis- and trans- 1,2-diaminocyclohexanes 220. The receptor 221 has been also synthesized by this route [103] (Scheme 33). 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Scheme 43 Synthesis of enantiopure ring-substituted 1,2-diaminocyclohexanes by transition metal catalyzed and promoted cyclization of 1,7-octadienes...

These different catalysts were first tested in the desymmetrization of the achiral triene 63 (Scheme 40). The best enantioselectivities (up to 39%) were obtained with complexes 60b and 61c-d bearing carbene ligands derived from 1,2-diphenyl-1,2-diaminoethane (R = Ph). ligands derived from 1,2-diaminocyclohexane gave poor enantioselectivities (< 9% ee). Replacement of the mesityl group in complex 60b by o-methyl- or o-isopropylphenyl groups (complexes 61c-d) slightly increases the enantioselectivity (from 13... 

Gawronski et al.21 have used NMR spectroscopy, especially NOE experiments in order to assign conformation of the chiral calixsalen-type macrocycles, products from the [3 + 3] cyclocondensation of the trans-1,2-diaminocyclohexane with hydroxydialdehydes. It was shown that the macrocycles had C3-symmetrical structure and s-syn conformation of imine C—H/cyclohexane axial C—H bond systems and s-trans conformation of the bis-imine unit. 

In Sn(II) complexes, the tin atom was located above the di-Schiff base coordination plane, while in Sn(IV) complexes, it was coplanar with the imine coordination framework. The position of the metal was supported by X-ray data. For the compounds studied, the 119Sn chemical shift values varied from 501.4 to —1015.9 ppm. Increase in the coordination number from Sn(II) to Sn(IV) led to an increase in the tin shielding. The differences of up to 3.0 ppm between 5119Sn values for the complexes, being derivatives of R,R and S,S 1,2-diaminocyclohexane, were observed. 

The disulfonamide library was tested in the TifO PrC-mcdiatcd addition of Et2Zn to aldehydes, a known process using the bis-trifluoromethylsulfonamide of 1,2-diaminocyclohexane.106 The tests were run in 30 different reaction vessels in parallel format. In order to increase throughput, each vessel was charged with four different aldehydes, and the enantioselectivities of the four reaction products were determined by conventional GC analysis of the crude mixtures. The idea of using a given catalyst to screen combinatorially the reactions of different substrates had previously been proposed but in a different context.45 In the present case each mixture required about one hour to be screened, which means that about 96 ee-determinations of products (52) (Scheme 11) could be performed per day.105 A total of 120 results were collected, the best ees being >90%. 

Moeller, T. and Hseu, T. M. (1962). Observations on the rare earths— LXXVI. The stabilities of the trans-1,2, diaminocyclohexane-N,N tetraa-cetic acid chelates of the tripositive ions, J. Inorg. Nucl. Chem. 24, 1635. 

Another platinum(IV) ammine complex studied as a possible anti-tumour compound is shown in Figure 3.101 [171] cis-( 1,2-diaminocyclohexane)tetra-chloroplatinum has undergone clinical trials but was found to be too neurotoxic. 

Other N6-cages also prepared include symmetrical derivatives of type (161), the unsymmetrically capped species (162) and (163) (Boucher et al., 1983 Bond, Lawrance, Lay Sargeson, 1983 Hammershpi Sargeson, 1983) and a number of related cages derived from 1,2-diaminocyclohexane rather than 1,2-diaminoethane (Geue, McCarthy Sargeson, 1984). 

FIGURE 1.1 Structures of organic compounds referred to in the text (a) sucrose (also known as saccharose), (b) dimethyl sulfoxide (DMSO), (c) dimethylformamide (DMF), (d) sorbitol, (e) mannitol, (f) nitrilotriacetic acid (NTA), (g) citric acid, (h) N,N,N, N -fran,s-1,2-diaminocyclohexane-tetraacetic acid (CyTA), (i) saccharic acid, (j) glutamic acid. 

Diaminocyclohexane, c354 1,10-Diaminodecane, d9 2,2 -Diaminodiethylamine, d362 1,12-Diaminododecane, d804... 

The second criteria, a different activity spectrum, is met by oxaliplatin (Figure 1.9A), the l isomer of [oxalatol f ra/rv-1,2-diaminocyclohexane)platinum (II)], oxaliplatin, [Pt(II)(oxalato)(DACH)]. This platinum agent is used for secondary treatment of metastatic colorectal cancer.77 Oxaliplatin, like carboplatin, has a kinetically slower leaving group, and is also less nephrotoxic than cisDDP. The limiting toxicity of oxaliplatin is peripheral sensory neuropathy, also seen with cisDDP. The neuropathy affects the extremities and increases in incidence and... 

Derivatization and enantiomeric excess determination of 1,2-diaminocyclohexane A 13 x 100-mm test tube is charged with 25 mg of the... 

The aqueous filtrates may be combined and saved for isolation of (S,S)-1,2-diaminocyclohexane as the bis-(+)-tartrate salt using an alternate procedure.2 The methanol washes can be discarded. 

The product of this preparation is the most enantioselective catalyst developed to date for asymmetric epoxidation of a broad range of unfunctionalized olefins.6 The procedure includes a highly efficient resolution of trans-1,2-diaminocyclohexane as well as a convenient analytical method for the determination of its enantiomeric purity. This method is general for the analysis of chiral 1,2-diamines. The Duff formylation described in Step B is a highly effective method for the preparation of 3,5-di-tert-... 

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