Pyridine derivatives, isomer separations

A novel synthesis of isoselenazoles (150), using bromoseleno-intermediates in the final cyclization stage, comprises the successive treatment, at -80 C, of selenoethers of type (148), e.g. cis-/3-methylseleno-2-propenal, with bromine and ammonia it generally affords the desired heterocycles in very good yield. The precursors (148) are ultimately derived from the appropriate ketones (146), which are first converted into the chloro-aldehydes (147) by the Vilsmeier-Haack reaction, and then treated with methaneselenol in pyridine-triethylamine. They arise as mixtures of cis- and trans-isomers, separable by spinning-band fractional distillation. The u.v. and n.m.r. spectra of the isoselenazoles were recorded and discussed. ... 

Reagents i, Bu OK Bu OH MeOCH Cl ii, NBS PhCO ) iii, MeCOSK-CH,Cl, iv, HCI-MeOH v, trithian derivative of p-MeOCsH CHO-BFj-CH, Clj vi, CK-aq. MeOH-R.T. vii, Mel-NaH xylene-heat viii, —78 °C Bu jAlH-EtjO ix, (COClij-EtjO x, nO C-GHjClj xi, I mol BuLi 110°C xii, cone. HC1-70°C xiii, separate isomers xiv, -78 "C-Bu jAlH-THF xv, AcjO-pyridine xvi, iodosobenzene diacetate-MeCN MejS xvii, aq. NaOH-MeOH-R.T. xviii, w-ClCgH COjH xix, BFj-EtjO-CHjCL-R.T. 

Bearing this in mind, we designed and synthesized a number of P-CD derivatives [27-34] which could i) bind copper(II) forming a multisite recognition system ii) show thermodynamic stereoselectivity in copper(II) ternary complexes iii) perform chiral separation of unmodified amino acid enantiomers. Among the monofunctionalized P-CD derivatives, only those functionalized in position 6 with diamines show chiral molecular recognition [29,32,35-37]. On the contrary, the P-CDs both functionalized in position 3 and those where a triamine was attached to the narrower rim of the toroid do not act as chiral receptors. 2-(aminomethyl)pyridine, histamine and NH3 molecules were used to obtain the three isomers of P-CDs (Figure 3), but only the A,BCD-NH2 molecule, coordinated to the copper(II) ion, is seen to have enatioselective effects on aromatic amino acids [38]. 

A large volume of work continues to be published in the area of thiazole chemistry. Physicochemical aspects continue to receive their share of attention, and interest in meso-ionic compounds has been sustained. Asinger and Offerman s versatile synthesis provides routes to reduced thiazoles (75, 212—217). Other notable methods employ thiirans (75, 218, 219), thiocarbonylamino-acid silyl esters (75, 220), and enamines (75, 221) as starting materials. Reduced thiazoles play an important role in peptide and protein studies (75, 234—239), and generate interest because of their occurrence as structural units in compounds of physiological interest, such as the antibiotics bacitracin A (75, 147 - 149) and thiostrepton. Benzothiazole derivatives have been employed to separate amidines for the first time into their syn- and fl/itZ-isomers (74, 49). The reaction of citric acid with penicillamine provides an interesting entry into the thiazolo-[3,2-fl]pyridine system (74, 152). 

Bruceolline F 18, an A/ -glucosyl-indole, has been isolated from root wood of Brucea mollis Stable, separable atropisomers of the -glucosyl-pyrrole derivative 19 were obtained by elaboration of 2,3,4,6-tetra-(7-pivaloyl-p-D-glucopyranosyIamine (i, PhCMXXOEt)=M(CO)s where M=Cr or W ii, Bu NC) the isomers result from restricted rotation about the glycosidic bond." N-Gluco- and galactosyl-pyridine-2(lH)-thione derivatives such as 20 have been synthesized by... 

The TLC of optical brighteners or bleaches, derived from 4,4 -diaminostilbene-2,2 -disulphonic acid, has been described by Theidel [86]. He was able to separate the cis and trans isomers on polyamide layers, using methanol-ammonium hydroxide-water (66 + 27 + 7) surprisingly the cis-compound migrated ahead of the trans-. The opposite order was found in TLC experiments of Latestak [50] on silica gel G, using the solvents n-propanol-5% sodium bicarbonate solution (66 + 33), n-butanol-pyridine-water (33 + 33 + 33) and amyl alcohol-p3n idine-25 % ammonium hydroxide (33 + 33 + 33). The substances were detected by observation in UV light. 

Not only chiral phases but also common stationary phases have been used for the separation of DL-pantolactone isomers. Takasu and Ohya (79) described the separation of MTPA derivatives (Fig. 27) of pantolactone isomers employing a packed column containing 2% OV-17 (Fig. 28). MTPA derivatives were prepared using a 5 5 2 (v/v/v) mixture of l,2-dichloroethane-(-)-a-methoxy-a-(trifiuoromethyl)-phenylacetyl chloride (MTPAC)-pyridine (at 80°C, for 30 min). AT-Trifiuoroacetyl-L-prolyl and some other derivatives were also tested but did not give adequate separation. 

Heating readily prepared l,4-di-0-benzoyl-D,L-myo-inositol in a pyridine-water mixture effects a migration of the benzoate groups giving rise to all nine possible isomeric diboizoate derivatives. The mixture could be separated by a combination of fractional crystallization and silica gel chromatography into each pure individual dibenzoate isomer which after subjecting to a phosphorylation-... 

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