A novel synthesis of benzofuran and related compounds. III. The vilsmeier reaction of phenoxyacetaldehyde diethyl acetals

A novel synthesis of 2-benzofurancarbaldehydes by the Vilsmeier reaction of phenoxyacetaldehyde diethyl acetals is described.     

A novel reaction of vilsmeier reagent with 2,1-benzisoxazoles

Vilsmeier reagent reacts with 2,1-benzisoxazoles affording N-formanilides in high yields.     

Formation of benzofuran and 2H-chromene structures in one reaction. A novel synthesis of 2H-chromene derivatives

Heating the morpholinal of nitrosalicylic aldehyde with methyl propiolate in acetonitrile in the presence of Cul affords an equimolar mixture of 2-methoxycarbonylmethyl-3-morpholino-5-nitrobenzofuran and 3-methoxycarbonyl-2-morpholino-6-nitro-2H-chromene, the structures of which were determined by X-ray analysis. Only the 2H-chromene mentioned above was obtained in the absence of Cul and solvent.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1222–1228, May, 1996.     

Organosilicon compounds I. A novel synthesis of organosilicon substituted furfurals

The use of the diethylacetal moiety of 2-furfuraldiethylacetal as a carbonyl blocking agent during n-butyllithium metalations is described. The synthesis of 5-silicon substituted furfurals is accomplished for the first time with NMR data being employed as a means of structure proof. Furthermore, the isolation of the uniquely stable organo-lithium salt, 5-lithio-2-furfuraldiethylacetal, is reported.     

Syntheses of salvilenone and related compounds: I. A total synthesis of salvilenone

The first total synthesis of a novel phenalenone diterpene salvilenone (1) isolated from a traditional Chinese medicine, Dan-Shen (Salvia miltiorrhiza. L.), has been achieved in thirteen steps started from resorcinol dimethyl ether (5).     

Research on heterocyclic compounds. XLII. The vilsmeier reaction in the synthesis of imidazo[1,2‐a]pyrimidine derivatives

The Vilsmeier reaction on imidazo[1,2‐a]pyrimidine ring is reported. The 3‐formyl derivative obtained is oxidized to yield the corresponding carboxylic acid.     

The reaction of carbohydrates with triphenyl phosphite methiodide and related compounds : A new synthesis of deoxysugars

Triphenyl phosphite methiodide and related compounds are proposed as reagents for replacing hydroxyls of protected carbohydrates by halogen atoms. The ease of the substitution reaction depends on steric accessibility of the hydroxyl to an S_N2 attack. Isopropylidene and benzylidene as well as ester protective groupings can migrate under the reaction conditions; possible mechanisms of these migrations are discussed. As a result, a new route to deoxysugars starting from partially methylated or tosylated monosaccharides has been developed.     

The synthesis of thiaolivacine and related compounds

1,5-Dimethylbenzothieno[2,3-g]isoquinoline (thiaolivacine) has been prepared from the nitro-vinyl derivative of 4-methyl-3-dibenzothiophenecarboxaldehyde. Using the same aldehyde, 4-des-methylisothiaolivacine was prepared by formation of the Schiff's base with aminoacetaldehyde diethyl acetal followed by cyclization. Similar methods yielded the pyrido-N-isomer, 1-des-methylthiaolivacine, from 4-methyl-2-dibenzothiophenecarboxaldehyde. The thiaolivacine parent unsubstituted ring system, benzothieno[2,3-g]isoquinoline, was prepared from 2-dibenzothio-pheneearboxaldehyde by the aminoacetaldehyde approach, as was the corresponding oxygen analog, benzofuro[2,3-g]isoquinoline, from 2-dibenzofurancarboxaldehyde. The 100 MHz spectra of these fused isoquinolines are recorded and correlated.     

A simple synthesis of tropones and related compounds

Cyclohexa-2,4- and 2,5-dienones bearing at position 2 or 4 α dihalomethyl group (halogen = chlorine or bromine) are smoothly reduced by tri-butyltin hydride to furnish appropriately substituted tropones. Modification of the substituents permits access to a tropolone and to less substituted tropones. The mechanism of this ring expansion process has been discussed.     

Stereospecific synthesis of mexiletine and related compounds: Mitsunobu versus Williamson reaction

Mexiletine [1-(2,6-dimethylphenoxy)-2-propanamine], a chiral, orally effective antiarrhythmic agent, and several analogues substituted on either the stereogenic centre or the xylyloxy moiety, were prepared in both, highly enriched, optically active forms. According to the ‘chiral pool’ approach, the appropriate amino alcohols, protected as the corresponding phthalimide derivatives, were condensed with the desired phenols under either Mitsunobu (method A) or Williamson (method B) conditions. Generally, method A provided the most efficient route, both in terms of yields and number of steps necessary. Only when an isopropyl group was present on the stereogenic centre, i.e. when 2-amino-3-methylbutanol was used as the starting alcohol, method B proved to be the only available route, method A giving no product other than the starting phthalimide derivative. Regardless of the method used, enantiomeric excesses ranged from 91 to 99%. Given the availability of both variously substituted phenols and optically active amino alcohols, the two methods described herein, taken together, may serve as a versatile approach, useful to meet the needs of new chiral, optically active mexiletine analogues, possibly endowed with higher potency in exerting a use-dependent block on sodium channels and/or more resistant to biotransformations.     

Studies on quinoline derivatives and related compounds. VI. A novel displacement reaction of 1-ethylquinolinium iodides with nucleophiles

The reaction of 4-amino- ( 3a ) and 4-anilino-3-carbethoxy-1-ethyl-6,7-methylenedioxy-quinolinium iodide ( 3b ) with nucleophilic reagents produced 7-substituted 4-amino-3-carboxy-1-ethyl-6-hydroxyquinolinium betaines ( 5b-d ) and 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-phenylimino-3-quinolinecarboxylic acid ( 6b-d ), respectively, which led to 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-oxo-3-quinolinecarboxylic acids ( 1b-d ) by alkaline hydrolysis. With a variety of 1-ethyl-1,4-dihydroquinoline carboxylates ( 16a-e ) these novel displacement reactions were attempted.     

Organotin compounds I. The synthesis of dibutyltin dihalides

The direct reaction between butyl iodide and tin to give dibutyltin diiodide was investigated. It was found that extremely active catalysts for this reaction are provided by combinations of metal halides and oxygenated solvents. Either component alone has little or no catalytic effect but combination gives high yields of dibutyltin diiodide. The metal halide can be added as such, or alternatively a metal or salt which can readily be converted to a halide under the conditions of reaction may be used. Of the metals investigated, lithium appears to be the most active. The results suggest that all oxygen-containing solvents are effective co-catalysts with the metal halides, and that the oxygen-containing co-catalysts may have greater activity if they contain more than one oxygen atom in the molecule.