Conformation 1,2-diamines

Table 3 fists cycloaliphatic diamines. Specific registry numbers are assigned to the optical isomers of /n t-l,2-cyclohexanediamine the cis isomer is achiral at ambient temperatures because of rapid interconversion of ring conformers. Commercial products ate most often marketed as geometric isomer mixtures, though large differences in symmetry may lead to such wide variations in physical properties that separations by classical unit operations are practicable, as in Du Font s fractional crystallisation of /n t-l,4-cyclohexanediamine (mp 72°C) from the low melting (5°C) cis—trans mixture. 

In the case of 1,2-dibenzoylbenzene systems 3, however, it is possible to obtain the 1,4-diazocine derivatives 4 on reaction with benzene-1,2-diamines.13 - 18 The eight-membered ring exists in a tub conformation, which exhibits such a high inversion barrier that in the case of unsym-metrically substituted systems it is possible to isolate the corresponding enantiomers. 

These observations indicated that an intermolecular double condensation to give a bis N-(methylene-4-oxocoumarinyl)-l,4 aromatic diamine had occurred. Data from the elemental analysis indicated that the calculated and observed values were within the acceptable limits ( 0.4%) and in conformity with the assigned structure. In the addition of molar equivalents of 1,4-aromatic binucleophilic compounds to compound 72 we did not observe any heterocyclic compounds resulting from the further intermolecular nucleophilic attack on the single condensation product. Since the condensation of 3-(dimethylaminomethylene)-chromane-2,4-dione with aromatic binucleophilic compounds is the only route to the new coumarinic compounds, this represents a useful synthetic method. 

To round out this group of drugs in which the piperazine ring appears to serve primarily as a basic spacer unit, or a conformationally restricted ethylene-diamine unit, reaction of N-phenylpiperazine (135) with acrylonitrile produces nitrile 136. Conversion... 

The simplest case for complete enforcement of the convergent conformation was provided by meta xylidine diamine 10. Condensation of two triacids with this amine in the melt gave excellent yields of the dicarboxylic acid 11 (Eq. (2)). The architectural cliche is easily repeated in the naphthalene series to provide 12 and in the acridine series to provide 13. The latter is derived from the commercially available acridine yellow at very low cost. 

Along another line of work in our group (S,S)-l,4-bis(dimethylamino)-2,3-dimethoxy butane (DDB), which had been used as cosolvent in asymmetric synthesis [113], was tested as a core moiety for a dendritic amine catalyst. The conformationally flexible DDB-core, which has been synthesized in five steps from diethyl tartrate was coupled with different branches to give dendritically expanded diamines 90-92 (molecular weight 3800 Da) [114] (Fig. 32). 

The diamines and their mono- and di-protonated ions can exist in various conformations, in which the nitrogen lone pairs and the protons on nitrogen are directed in (i or i+) or directed out (o or o+) from the molecular cavity. Diprotonated l,10-diazabicyclo[8.8.8]hexacosane, for example, may exist in either of the three forms in equation (79). When the out-out isomer of l,10-diazabicyclo[8.8.8]hexacosane bis hydrochloride (o+ o+) is dissolved in aqueous acidic solution, isomerisation to the in-in isomer (i+ i+) occurs so... 

Medium-ring bicyclic diamines have now been prepared and their proton transfer behaviour has been investigated (Alder, 1983). The diamine 1,6-djflza-bicyclo[4.4.4]tetradecane [73] is reluctant to undergo outside-prptonation, presumably because outward pyramidalisation of the nitrogen atoms intro duces strain the diamine exists in the in-in conformation. The strain involved... 

The next linear diamine, 1,3-propanediamine (PDA), was also studied by the same force fields. Four conformational families were considered and defined by the two... 

Lone-pair (n/n) interactions have been studied exhaustively on various diamines98,104-106 including 1,3-diamines and imidazolidines. Since n/n interactions usually are conformation-dependent66,67, from the PE spectra some information about the conformational properties of such compounds may be obtained. A thorough data compilation has been published by Mayer and Martin107. 

Metal salen complexes can adopt non-planar conformations as a result of the conformations of the ethane-1,2-diyl bridge. The conformations may have Cs or C2 symmetry, but the mixtures are racemic. Replacement of the ethylenediamine linker by chiral 1,2-diamines leads to chiral distortions and a C2 chiral symmetry of the complex due to the half-chair conformation of the 5-membered ring of the chelate. Depending on substitution at the axial positions of the salen complex, the symmetry may be reduced to Q, but as we have seen before in diphosphine complexes of rhodium (Chapter 4) and bisindenyl complexes of Group 4 metals (Chapter 10) substitution at either side leads to the same chiral complex. Figure 14.10 sketches the view from above the complex and a front view. 

Perhaps the simplest two-site cooperative systems are small molecules having two binding sites for protons, such as dicarboxylic acids and diamines. Despite their molecular simplicity, most of these molecules do not conform with the modelistic assumptions made in this chapter. Therefore, their theoretical treatment is much more intricate. The main reasons for this are (1) there is, in general, a continuous range of macrostates (2) the direct and indirect correlations are both strong and intertwined, so that factorization of the correlation function is impossible. In addition, as with any real biochemical system, the solvent can have a major effect on the binding properties of these molecules. 

Five- and six-membered rings formed by coordination of diamines with a metal ion have the stereochemical characteristics of cyclopentane and cyclohexane. The ethylenediamine complexes have puckered rings and the trimethylenediamine complexes have chair conformations. The methylene protons are nonequivalent in these nonplanar conformations, taking on the character of equatorial and axial substituents. They are made equivalent as the result of rapid conformational inversion at room temperature, just as in the alicyclic compounds (Fig. 7.1). This has been observed in nmr studies of planar and octahedral complexes of ethylenediamine-type ligands with a number of metals. 

A number of substituted propane-l,3-diamine (64) compounds of the type [PtL2] and [PtX2L2] (X = Cl, Br, or NH3) have been described. Several of the latter species exhibited polymorphism which was attributed to either different H-bonded linkages or different chelate ring conformations in the two forms.In solution their n.m.r. spectra are consistent with a preference for a chair-type conformation with the Cl or OH axial.Similar n.m.r. spectral studies have also been reported for some related N-methyl substituted... 

A-Boc-A -isopropylimidazolidine (175) is deprotonated by the (—)-sparteine method and alkylated to form imidazolidines 176 (equation 41). The yields remain below 50%, since only a part of 175 exists in the shown conformation, which is required for the directed deprotonation. At low temperature, the interconversion between the s-trans- and i-c -conformation is too slow. Ring cleavage furnishes synthetically useful chiral 1,2-diamines 177. 

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