Trans-l,2-diaminocyclohexane

Preparation of ligand 31 Originally, chiral ligand 31 was prepared from (1R,2R)-1,2-diaminocydohexane 33 based on the racemic synthesis reported by Barnes et al. in 1978 [15], where picolinic acid 34 was activated with P(OPh)3 and then coupled with trans-l,2-diaminocyclohexane. The reported isolated yield in the case of racemate was only 47%. We optimized the preparation as shown in Scheme 2.8 [16]. Picolinic acid 34 was activated with CDI in THF. After confirmation of activation, chiral diamine 33 was added to the solution. When complete, the reaction was quenched via the addition of a small amount of water (to quench excess CDI). The reaction solvent was then switched from THF to EtOH, when the desired ligand 31 directly crystallized out. Ligand 31 was isolated in 87% yield by simple filtration of the reaction mixture in high purity. With a 22 litter flask, 1.25 kg of 31 was prepared in a single batch. 

With the addition of both enantiomers of the chiral trans-l,2-diaminocyclohexane both enantiomers ofa chiral amino-monoadducts could be isolated (Figure 3.9). The circular dichroism spectra of the two enantiomers show a very intense chirospectroscopic response [91]. 

Thio)ureas Derived From Trans-l,2-Diaminocyclohexane and Related Chiral Primary Diamines... 

CDTA trans-l,2-diaminocyclohexane-N,N,N,N-tetraacetic acid CMP cytidine S -monophosphate... 

Few steps from ennantiomerically pure trans-l,2-diaminocyclohexane... 

Because of the weaker nature of the H-bonds between amines and alcohols, compared with more polar amidic H-bonds, supraminols are compatible with hydrophobic environments when crystallized, although this is not a requirement. The supraminol helical trans-l,2-diaminocyclohexane-C02 complex can be recrystallized from aqueous ethanol [51]. 

BBBAN = 2,7-bis-l,8-2-naphthyridine BEAN = 2,7-bis-(V,Ai -diethylaminomethyl)-l,8-naphthyridme BPMAN = 2,7-bis[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyri-dine BPMCN = AJ,AJ -bis(2-pyridylmethyl)-AJ,V -dimethyl-trans-l,2-diaminocyclohexane dxlC02H = 2,6-Bis[(2,6-dimethylphenyl)methyl]-4-tgrt-butylbenzoic acid ENDOR =... 

The X-ray analysis of the complexes (-)5g9-bis[(s,s-trans-l,2-diaminocyclohexane)]-(R,R)-trans-l,2-diaminocyclohexaneo)balt(ni) chloride pentahydrate, (—)s89-(.lel2,ob)-[Co(chxn)3]Cl3 5H20 and (-)5g9-bis[(lR,2R)-l,2-diaminocyclohexane](3,3 -dimethyl-2,2 -bipyTidyl)cobalt(in) bromide diperchlorate monohydrate, (-)58 -[Co(R,R-chxn)2(3,3 -dmbpy)]Br(C104)2 shows that in both cases the molecules... 

K. Hanabusa, M. Yamada, M. Kimura, H. Shirai, Prominent Gelation and Chiral Aggregation of Alkylamides Derived from trans-l,2-Diaminocyclohexane , Angew. Chem. Int. Ed., 35, 1949 (1996)... 

Unequivocal syntheses of cis- and frans-eff-decahydroquinoxalines have been achieved by lithium aluminum hydride reduction of the corresponding cis- and frans-decahydroquinoxalin-2-ones. The latter compounds were prepared by condensation of chloroacetic acid and cis- and trans-l,2-diaminocyclohexane, respectively. The resolution of trans-dZ-decahydroquinoxaline was effected by use of first di-benzoyl-d-tartaric acid and then of dibenzoyl-f-tartaric acid.100 (C/. p. 215.)... 

Gasparrini, F., Misiti, D.,Villani, C. Chromatographic optical resolution on trans-l,2-diaminocyclohexane derivatives Theory and applications. Chirality, 1992, 4, 447-458. 

J. H. Dahl, D. Espersen, and A. Jensen, Diffential Kinetic Analysis and Flow Injection Analysis. Part 1. The trans-l,2-Diaminocyclohexane-Tet-raacetate Complexes of Magnesium and Strontium. AnaL Chim. Acta, 105 (1979) 327. 

FIGURE 11. Electronic absorption (UV) and circular dichroism (CD) spectra in acetonitrile neutral (solid line) and protonated (dashed line) bis(Schiff) base (/ ,/ )-134 prepared by condensation of julolidinecarboxaldehyde (131) with (R)-trans-l,2-diaminocyclohexane [(/ ,/ )-133]. Reproduced from Reference 116 by permission of VCH Publishers... 

The enantiomer (+)-trans-l,2-diaminocyclohexane was kindly provided by Prof. 

Mioskowsld built up a chiral acylating reagent 41 [N-acetyl-l,2-bis (ttifluoromethanesulfonamide)j from trans-l,2-diaminocyclohexane [51]. This active amide that proved to be insensitive to hydrolysis could resolve various primary amines in either polar or apolar solvents, at or below room temperature. As a typical example, 1-phenylethylamine reacted in N,N -dimethylpropylene urea (DMPU) at —20 °C, to give, at fuU consumption of the reagent, after 24h reaction, 33% of recovered amine with 90% ee. 

Recently complexes such as 13 and 14 have been prepared. They are based on the coupling of the DACH-Pt [(R,R)-trans-l,2-diaminocyclohexane-platinum(II)] fragment, the active part of oxaliplatin which is used in the treatment of colorectal cancer [64, 65], to tamoxifen (Scheme 3.6) [66]. 

In recent years, many groups have employed the click reaction in the supramolecular environment of organogels and hydrogels. One such example is in the stabilization of low molecular weight organogelators 14 and 15 based on the undecynylamide of trans-l, 2-diaminocyclohexane... 

Maleic copolymers were proved to form chelates with platinum-containing anticancer drugs (cis-diamminedichloroplatinum(II), trans-l,2-diaminocyclohexane platinum) through a monocarboxylato and a 0->Pt coordination linkage. These complexes self-assembled into nanoparticles with an increased in-vivo tumors inhibition due to their internalization into the cancer cells. The release of the platinum-containing drug was pH dependent [211,212]. 

Cl 8Hi,8N90i 2Rh, ( + )-Tris-( (-)-trans-l, 2-diaminocyclohexane)rhodium-(III) nitrate trihydrate, 40B, 903 Cl8H52CI3C0N6O5, (-)589"Tris(+trans-1,2-diaminocyclohexane)cobalt-(III) chloride pentahydrate, 35B, 713 Cl8H52CI3C0N6O5, Bis((S,S)-trans-1,2-diaminocyclohexane)-(R,R)-trans-1,2-diaminocyclohexanecobaltdII) chloride pentahydrate, 43B, 1151... 

Gasparrini F, Misiti D, Villani C, La Torre F, Sinibaldi M (1988) High-performance liquid chromatography on chiral packed microbore columns with the 3,5-dinitrobenzoyl derivative of trans-l,2-diaminocyclohexane as selector. J Chromatogr A 457 235-245 Uray G, Lindner W (1990) (S,S)-diphenyl-ethanediamine (DPEDA) derivatives as chiral selectors Part I. Undecenoyl bound dinitrobenzoyl-DPEDA as a broadly applicable chiral stationary phase. Chromatographia 30 323-327... 

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