DZ-Tartaric acid

In principle, separation of resonances of diastereomeric compounds (such as dl and meso isomers) may be increased simply through use of an appropriate achiral solvent. Chiral solvents may in some cases be especially effective in producing a separation, particularly if the diastereomers differ in configuration about a center that is amenable to analysis by the CSA method. Kaehler and Rehse (89) give a detailed account of conditions necessary for measurement of the ratio of meso- and dZ-tartaric acid employing A,N-dimethyl PEA. Bomyl acetate used as solvent for l,2-difluoro-l,2-dichloroethane (90) allows measurement of the diastereomeric composition. Paquette and co-workers (91,92), using TFAE, were able to determine the diastereomeric purity of the recrystallized adducts 47 of... 

By a modified Bischler-Napieralsky reaction, 6 -nitrophenylaceto-jS-3 4-methylenedioxyphenylethylamide, resulting from the condensation of -3 4-methylenedioxyphenylethylamine with 2-nitrophenylacetyl chloride, was converted into 6 nitro-l-benzyl-6 7-methylenedioxy-3 4-dihydroisoquinoline. The methiodide of the latter was reduced with zinc and hydrochloric acid to 6 -amino-l-benzyl-2-methyl-6 7-methylenedioxy-1 2 3 4-tetrahydro/soquinoline dihydrochloride, which by the Pschorr ring-closure reaction, produced dZ-roemerine (IV, p. 317), m.p. 85-7°. By treatment in succession with d- and Z-tartaric acids, the dZ-base was resolved into Z- and tZ-forms. Synthetic Z-roemerine is dimorphic, m.p. 85-7° and 102°, and has [aju — 79-9° (EtOH), these constants being in good agreement with those of the natural base. 

In an analogous manner 3-hydroxy-N-methylmorphinane [nxxm] was prepared from [lxxii], and when [lxxiv] was heated with hydrochloric acid at 120° C. cyclization and partial demethylation occurred, the product being dl-tetrahydrodesoxycodeine [lxxv], identical with the racemate prepared from the separate d and l isomers obtained from sinomenine and codeine respectively. The racemate was resolved by d-tartaric acid [24], Complete demethylation occurred when the cyclization was effected with hydrobromic acid, the product being dZ-tetrahydrodesoxymorphine [24],... 

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.)... 

Structure and Synthesis. In addition to the proof of the structure of tetrahydropalmatine by virtue of its preparation from palmatine and the reverse oxidation, the resolution of the dZ-base was accomplished by means of d- and Z-tartaric acids in succession, the d-base d-tartrate and the Z-base Z-tartrate being the forms of least solubility (225). The d- and Z-bases had [a]n +291° (ethanol) and —294° (ethanol), respectively, the natural d-base having [a] +292.5° (58). Spath and Mosettig (226) have also related tetrahydropalmatine directly to tetrahydroberberine, that is to canadine. The d-, Z-, and dZ-forms of canadine were demethylenated by means of phloroglucinol and sulfuric acid yielding the base XXX in its three possible forms, the d-form having +307° (ethanol). These when... 

Structure and Synthesis. When Buck and Perkin (228) attempted to apply the Pictet and Gams synthesis (220) of berberine to epiberberine they obtained an isomer, tetrahydro- -epiberberine (XXXIII). Subsequently, Haworth and Perkin achieved a total synthesis which is detailed in connection with the synthesis of cryptopine. Oxidation of sinactine with iodine in boiling alcohol yields epiberberinium iodide, from which the chloride was prepared by treatment with silver chloride, and this was identical with epiberberinium chloride prepared from cryptopine (235). Finaly, Spath and Mosettig (236) resolved the dZ-tetrahydroepiberberine (m.p. 170°) (XLIII) from cryptopine by means of d- and Z-tartaric acids in succession and showed that the Z-form, [a] —302° (chloroform), was identical with the natural alkaloid. The cZ-form had the same numerical value for its optical rotation and melted at 178-179°. 

It was possible to racemize bulbocapnine 0-methyl ether and 0-benzoyl-bulbocapnine by first oxidizing with iodine and subsequently reducing with zinc in dilute acid. The dZ-O-methyl ether melted at 136° and was resolvable into the I- and d-derivatives ([a] d 247° in chloroform) by means of d- and Z-tartaric acid, respectively. Hydrolysis of the dZ-O-benzoylbulbo-capnine (m.p. 201-202°) with sodium methylate yielded dZ-bulbocapnine (m.p. 209-210°). As in other aporphines, it was possible to effect scission of the nitrogen ring in bulbocapnine by treatment with benzoyl chloride at its boiling point. 

The synthesis of laureline (92) from 3,4-methylenedioxyphenethylamine and 2-nitro-4-methoxyphenylacetic acid offered no unusual features, and the purification of it was facilitated by the very sparing solubility of its hydrochloride. Resolution of the synthetic base was easily achieved by means of d- and J-tartaric acids. The tartrates crystallized readily from ethanol and the Z-base cZ-tartrate and the d-base Z-tartrate were the sparingly soluble ones (m.p. 210-211°, [ ]d +24°). The former was identical with natural Z-laureline d-tartrate, and the base (m.p. 114°) regenerated therefrom was identical with Z-laureline. A Hofmann degradation on synthetic dZ-laureline yielded products which were identical with those obtained from the natural alkaloid, and therefore it has structure XXXIV. 

Marion and Grassie (103), evidently unaware of this synthesis, repeated it using the same precursors as those already used. They did however resolve the dZ-base with d- and with Z-tartaric acids and obtained the natural Z-roemerine, [a] d —79.9°, as well as d-roemerine, [a] - -80.2°. Roemerine exhibits dimorphism a low-melting (87°) form was at first obtained, but later when the form melting at 102° was obtained only that form could be crystallized. 

The Z-base-d-acid salt no longer can be obtained pure when the solution contains about equal proportions of the salts of d- and Z-amines. For this reason, also, an initial resolution of the dZ-amine with d-tartaric acid is not feasible. 

The present method is adapted from that of Loven.1 The resolution has been carried out with d-a-bromocamphor-ir-sulfonic acid (Z-form) 2 3 with Z-and dZ-malic acids (d- and Z-forms) 4 with Z-quinic acid and d-tartaric acid (d- and Z-forms),5 and with d- and Z-6,6 -dinitrodiphenic acids (d- and Z-forms).6 Methods employing d-benzylmethylacetyl chloride,7 d-oxymeth-ylenecamphor,8 Z-quinic acid, and d-camphoric anhydride 10 are of theoretical interest only. The dZ-amine is not resolved by the active camphor-io-sulfonic acids 11 or mandelic acids.12... 

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