Diamino cyclohexanes

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). 

Diamine chelate complexes are more stable than the monodentate amine heterocycles and, therefore, can be studied under physiological conditions. The imidazole complexes are unstable in aqueous solution and decompose rapidly to technetium oxide hydrate. Six-membered ring chelates are significantly less stable than five-membered ones. Lesser flexibility of the ligand, such as 1.2-diamino-cyclohexane, parallels somewhat lower stability of the complex [53] ... 

Ke and Regier [71] have described a direct potentiometric determination of fluoride in seawater after extraction with 8-hydroxyquinoline. This procedure was applied to samples of seawater, fluoridated tap-water, well-water, and effluent from a phosphate reduction plant. Interfering metals, e.g., calcium, magnesium, iron, and aluminium were removed by extraction into a solution of 8-hydroxyquinoline in 2-butoxyethanol-chloroform after addition of glycine-sodium hydroxide buffer solution (pH 10.5 to 10.8). A buffer solution (sodium nitrate-l,2-diamino-cyclohexane-N,N,N. AT-tetra-acetic acid-acetic acid pH 5.5) was then added to adjust the total ionic strength and the fluoride ions were determined by means of a solid membrane fluoride-selective electrode (Orion, model 94-09). Results were in close agreement with and more reproducible than those obtained after distillation [72]. Omission of the extraction led to lower results. Four determinations can be made in one hour. 

Figure 58 Partial 13C NMR spectra for (R,R)-trans-1,2- diaminocyclohexane-( )-irani-l, 2-cyclopentanediol and (R)-l,l -bi-2-naphthol adducts. Left (a) (R,R)-trans-1, 2-diaminocy-clohexane (b) inms-( )cyclopentanediol (c) 1 1 adduct between (R,R)-trans-1, 2-diamino-cyclohexane and tranx-( )-cyclopentanediol (d) 0.5 1 adduct between (R,R)-trans-1, 2-diaminocyclohexane and Znms-(+/-)-cyclopentanediol. Right (a) (R,R)-trans-1, 2-diami-nocyclohexane (b) 1 1 adduct between (i )-l,l -bi-2-naphthol and trans-( )-1, 2-diaminocyclohexane (c) 1 1 adduct between R,R)-trans-1, 2-diaminocyclohexane and (2 )-1,1 -bi-2-naphthol (e.e. 35%) showing molecular recognition and chiral discrimination of the diastereomeric supraminols (d) 1 1 adduct between (R)-l,l -bi-2-naphthol and (R,R)-trans-1, 2-diaminocyclohexane [60],...

Others CPSs have been prepared in a similar way and characterized at different steps by physicochemical methods. For example, the structure of the chiral selector iV-[2 -(5)-hydroxypropyl]-Ar, /V -bis(3,5- dichlorobenzoyl)-(f ,f )-tra i- 1,2-diamino-cyclohexane was solved by X-ray analysis and its absolute configuration confirmed unambiguously [73]. These CPS phases were used to resolve a large number of racemic mixtures belonging to different classes of organic compounds, such as a-aryloxyacetic acids, alcohols, sulfoxides, selenoxides, phosphinates, amino acids, amino alcohols, etc. 

As we have seen in Chapter 1, it is very difficult to introduce chirality in the inamedi-ate vicinity of the carbene centre [23,24,46], An elegant way to circumnavigate this is to introduce a functional group on the carbene that can act as the carrier of chirality in the metal complex (see Figure 2.6). Excellent examples are a Cp scaffold for planar chiraUty [47 9] or the binaphthyl group for axial chirahty [50-52], The tether itself can be used as the chiral backbone as is the case in functionalised carbenes derived from 1,2-diamino cyclohexane [53,54],... 

Although the hemilabile behaviour of the imino functional group together with an apparent isomerisation process on palladium may make it difficult to achieve high chiral resolution (ee) in asymmetric catalysis. Bonnet and Douthwaite developed an imino functionalised carbene ligand system based on the diamino cyclohexane framework that has achieved ees of up to 92% in palladium catalysed allylic alkylatiou reactions using ( )-l,3-diphenylprop-... 

Figure 3.47 Synthesis of a chiral imino functionalised NHC ligand from a 1,2-diamino cyclohexane scaffold.

The 2-chloro-imidazolium salt is accessible from the corresponding thione that can be synthesised by Kuhn s method [260] from the diamine. Using a chiral 1,2-diamino-cyclohexane scaffold produces a chiral samrated carbene. 

Another interesting approach to an NHC ligand with a chiral, bridging wingtip group was introduced by Perry et al. [45] and uses enantiomerically pure 1,2-diamino-cyclohexane as the scaffold. Reaction with chloroacetic acid chloride and subsequently with DIPP-imidazole yields the imidazolium salt that can be reacted with silver(I) oxide [46] to the respective silver(I) NHC complex. Subsequent carbene transfer to palladium(II) renders the chiral palladium(II) carbene transfer that can be used in catalysis (see Figure 5.9). 

Finally, the Mannich reaction may be applied to the. synthesis of reactive amines used as crosslinking agents of epoxy resins. The process requires the availability of molecules possessing more than two NH groups, which are obtained by reaction of polyfunctional substrates with polyfunctional primary amines (oligomeric polyalkyle-ncamines, diamino cyclohexane, etc.) - (see also 422, Chap. Ill, C). 

Boron was removed from distilled water by using a column of Dowex-1 (OH -form). For the photometric determination as a boron-curcumin complex, interfering ions were removed on small columns of Dowex-1 (formiate) and Dowex-50 (Na ) For the evaporation and ashing step, calcium hydroxide was used (recovery of one ng ca. 80%). By complexation of bivalent ions with 1,2-diamino-cyclohexane-NJ, N, N -tetra-acetic acid, water samples at pH 5.5 passed through a colunm of Dowex 50 W-X 8 (NH4) for the determination of barium Elution followed with 4 M nitric acid. Particular references for the separation of barium from sodium, calcium and sulfate are given. 

We noted in Chapter 10 two rather symmetrical arrangements of 7 nearest neighbours found in oxy- and fluoro-compounds of transition metals, namely, pentagonal bipyramidal (ZrF "), and monocapped trigonal prism (NbF ). The ions formed from ethylenediamine tetracetic acid and the closely related diamino cyclohexane acid are potentially sexadentate ligands, for there are 4 0 atoms and... 

Fig. 6.15 P reparative separation of the enantiomers of (a) a chiral c/s-diamino-cyclohexane derivative on Chiralpak AD (column 50 x 500 mm, injection 500 mg, flow rate 150 mL min ), and of (b) 0,0-dimethyl-2-benzyloxy-carbonyl-N-ethylamino-phosphate on Chiralcel OJ (column 100 x 500 mm, mobile phase heptane/ethanol 40/60, injection 4 g, flow rate 140 mL min ).

The complex prepared using (/ ,/ )-diaminocyclohexane (76) was four times less active and produced 1-phenylethanol in only 60% ee (S). The use of ethylenediamine (75) was even less active and decomposed after 40% conversion, possibly due to P-hydride elimination from a metal amide intermediate (Section 1.1.4). The diamino-cyclohexane moiety is quite flat and the ethylenediamine backbone is small, both leading to less steric interaction with the incoming ketone substrate. The rates for catalysts 77 and 78 with diethylphosphino substituents are lower than those with dia-rylphosphino substituents. These may form less active catalysts with less acidic NH groups (cf. Scheme 6). The active forms of complexes 67 and 74 appear to have optimum hydridicity and NH acidity resulting in high ATH activity. 

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