Hilbert-Johnson Products

The most reliable determination of the configuration of the Hilbert-Johnson products at the anomeric center consists in correlation with 

Baker trans rule or the Hudson isorotation rules have to be taken with care in view of some anomalies.11,38,39 Nuclear magnetic resonance spectra 38 and optical rotatory dispersion curves 38,40,41 have been recently applied to determine the configuration of pyrimidine nucleosides at the anomeric center. 

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The products of the mercuri process in most cases possess a C-V-C-2 -trans system in accordance to the Baker trans rule61-64 and are sterically more uniform than the Hilbert-Johnson products. On the other hand, certain anomers inaccessible by the mercuri process may be obtained under certain conditions (solvent) by the Hilbert-Johnson reaction as a mixture with the other anomer chromatographic methods have been worked out to separate these mixtures almost quantitatively into the individual anomers (cf. Section X). The Hilbert-Johnson reaction intermediates may be converted into nucleosides of both types, of the uridine type as well as of the cytidine type (cf. Section V), whereas conversion of the mercuri process of the uridine type into the cytidine type is somewhat tedious. On the whole, the Hilbert-Johnson reaction represents a suitable complementary method to the mercuri process. 

Both thermal and Hilbert-Johnson reactions occur quite readily in 2- and 4/6-alkoxyquinazolines. For example, distillation of 2,4-bis-/3-diethylaminoethoxyquinazoline in vacuo yields l,3-bis-/3-diethylaminoethylquinazolin-X4(l/J,3H )-dione (60JCS3546). A complicated example is furnished by heating a tetramethoxybipyrimidine with methyl iodide to give four separable products progressively (81AJC1157). 

Hetero Diels-Alder cycloaddition reactions, synthesis of natural heterocyclic products by, 42, 245 Heterodienophiles, new, heterocyclic synthesis using, 55, 1 Hilbert-Johnson reaction of 2,4-... 

The by-products which arose in the course of the Hilbert-Johnson reaction and were isolated either directly from the reaction mixture or after the usual work-up with alcoholic hydrogen chloride, hydrogen chloride in chloroform, or alcoholic ammonia might be divided into... 

Under conditions of the Hilbert-Johnson reaction, the 2,4-dialkoxypyrimidines (29) can furnish the following by-products uracil,13 1-alkyluracil,3-7 1,3-dialkyluracil,19 4-alkoxy-2(lIZ)-pyri-midinone,7 and l-alkyl-4-alkoxy-2(lH)-pyrimidinone.7,20 Thus, for example, 5-chloro-, 5-bromo-, and 5-iodouracil were isolated32- 33 as by-products in the Hilbert-Johnson reaction (in acetonitrile at 20°) of the corresponding 5-halo-2,4-dimethoxypyrimidines and 3,5-di-O-p-toluyl-2-deoxy-D-ribofuranosyl chloride. The formation of 1,3-dimethyluracil and 1,3,5-trimethyluracil as by-products has been observed quite recently19 when the reaction of 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride with 2,4-dimethoxypyrimidine and 5-methyl-2,4-dimethoxypyrimidine, respectively, was performed in toluene at 70°. 

The Anomeric Ratio op Products op the Hilbert-Johnson Reaction op Dimethoxyfyrimidines (54 and 55) with Halogenoses (56, 57, and 58) in Acetonitrile (Procedure A) and in Benzene (Procedure B)... 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

The example of a silyl—Hilbert—Johnson nucleosidation reaction in Section 25.3 is presumed to involve an intermediate ribosyl cation that is stabilized by intramolecular interactions involving the C2 benzoyl group. This intermediate blocks attack by the heterocyclic base from the a face of the ribose ring but allows attack on the j8 face, as required for formation of the desired product. Propose a structure for the ribosyl cation intermediate that explains the stereoselective bonding of the base. 

Chemical Properties.—Alkylation. Treatment of 3,5-diethoxy-l,2,4-thiadiazole (67) with benzyl bromide in boiling acetonitrile ( Hilbert-Johnson reaction ) slowly yields a monoalkylation product (68). Chloromethyl benzyl ether effects the alkylation rapidly in good yield. The use of ribosyl halides should make novel nucleosides accessible. ... 

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