CD EXCITON CHIRALITY METHOD : SCHIFF BASE AND CYANINE DYE-TYPE CHROMOPHORES FOR PRIMARY AMINO GROUPS

The C D exciton chirality method is a versatile and unambiguous method for the microscale determination of absolute configurations and conformations of organic molecules in solution. I t is particularly powerful when two different chromophores are involved since the coupled C D covers a wide spectral range and becomes a fingerprint for that compound. This paper describes the preparation, properties, and applications of threep-amino-substituted Schiff base chromophores to derivatize primary NH2 groups for the exciton chirality method; the Schiff bases are formed in high yield under mild conditions and yield chromophores which also couple with 0-acyl chromophores. Moreover, protonation of these Schiff bases yields cyanine-type chromophores exhibiting drastically red-shifted (ca. 100 nm) and 2-3-fold intensified C D couplets. The aldehydes p-(dimethylamino)benzaldehyde, julolidinecarbaldehyde, and p-(dimethy1amino)cinnamaldehyde form Schiff bases with aminocyclohexane to yield Chromophores-I, -11, and -111, respectively. These chromophores have the following A, , (e values) for the neutral and protonated species, respectively: Chrom-I, in MeCN 305 nm (24 300), in MeCN/TFA 395 nm (51 700); Chrom-11, in MeCN 331 nm (21 400), in MeCN/TFA 240 nm (48 300); Chrom-111, in MeOH 361 nm (37 000), in MeOH/TFA 460 nm (64 500). NH2 groups are converted into Schiff bases without protection of OH groups; in cases where N,O coupling was required, the OH was converted into the (4-methoxyphenyl)-2,4-pentadienoate (Chrom-IV), in MeOH 333 nm (40 000). All neutral Schiff bases and protonated Schiff bases of (1 R,2R)-tran~-cyclohexanediamine gave exciton-split C D curves with intense amplitudes. However, in the case of protonated Chrom-111, inversion of the CD sign occurred in 45 min a t room temperature in methanol and hence the CD should be measured soon after protonation; N M R and MM2 calculations show that the imminium bond in one of the protonated Schiff base chromophore undergoes an E 2 isomerization. Derivatives with Chrom-I and -11 do not isomerize, and amplitudes of the exciton couplet remain unchanged. Furthermore, the original substrate may be recovered quantitatively when derivatized with Chrom-I. Intense exciton coupling is still observed between chromophores with absorption maxima as far apart as 134 nm.