Pyridines 1,4-dihydro— from

While the synthesis of benzofuran derivatives from suitable furan derivatives has been comparatively little investigated, the synthesis of fused two-ring and three-ring compounds containing a pyridine nucleus from furan derivatives has been more successful furo[3,2-c]pyridines (345),752>753 2,3-dihydrofuro[2,3-a ]quinolines (from 4,5-dihydro-3-furoic acid),754 acrophyllin (346), and 7-hydroxydictamnine (347) (from ethyl 2-ethoxy-4-oxo-4,5-dihydrofuran-3-carboxylate),755 are examples of compounds in this class which have been prepared. 

Enzyme systems have been isolated from Escherichia coli and Aerobacter aerogenes which convert chorismic acid to 2,3-dihydroxybenzoic acid. The enzyme from Aerobacter aerogenes requires magnesium and NAD" for activity and is strongly repressed by low concentrations of iron or cobalt . Omission of the pyridine nucleotide from the enzymic reaction mixture allowed the conversion of chorismic acid to an intermediate (44), which itself was converted to 2,3-dihydroxybenzoic acid on the subsequent addition of The intermediate compoimd was isolated and identified as 5,6-dihydrocyclohexa-l,3-diene-1-carboxylic acid (44) for which the trivial name 2,3-dihydro-2,3-dihydroxybenzoic acid was suggested The structure of the intermediate was established... 

Pyridine, 4-(chloromethyl)-l,4-dihydro-4ff-azepines from, 7, 524 ring expansion, 7, 543-544 Pyridine, 2-chloro-6-trichloromethyl-as bactericide, 2, 514 Pyridine, 2-cyano-ions... 

While there are a number of related reactions that can assemble the pyridine nucleus, the oldest of these classical reactions is due to Arthur Hantzsch. In 1882 he reported the first synthesis of l,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates from a refluxing... 

Ring closure of 2-chloro-l-phenethylpyridinium ion (247) (prepared in situ) to l,2-dihydro-3,4-benzoquinolizium ion involves intramolecular nucleophilic displacement of the chloro group by the phenyl 77-electrons. A related intermolecular reaction involving a more activated pyridine ring and more nucleophilic 7r-electrons is the formation of 4-( -dimethylaminophenyl)pyridine (and benzaldehyde) from dimethylaniline and 1-benzoylpyridinium chloride (cf. Section III,B,4,c). 

Alternatively, the desethylcatharanthine can be obtained from the adduct 21 in the reaction of 2-(indol-2-yl)acrylate 20 and A-alkoxycarbonyl-1,2-dihydro-pyridine 8f(81CC37). 

E) Preparation of 2-( 1-Succinyloxyethyl)-3-Methyl-5-(2-Oxo-2,5-Dihydro-4-Furyl)Bemo[b] -Furan (409 CBj 8.65 grams of compound 3574 CB in 43 ml of pyridine are warmed for 30 minutes, on a water bath, with succinic anhydride. At the end of this, the pyridine is stripped off in vacuo. The mixture is treated with dilute sulfuric acid and with ether, the crystalline product filtered off, washed with water and with ether, and recrystallized from ethyl acetate (9.35 grams). MPq = 144°C (measured after drying at 90°C and 0.1 mm). Yield 77%. The product yields an equimolecular compound with morpholine. MPc= 136°C (from ethyl acetate). 

Curiously, 6-(chloromethyl)-4-methyl-2-methylene-3-phenyl-3-azabicyclo[4.1.0]hept-4-ene-l,5-dicarbonitrile (31), obtained from 4,4-bis(chloromethyl)-2,6-dimethyl-l-phenyl-1,4-dihydro-pyridine-3,5-dicarbonitrile, rearranges via 4-(chloromethyl)-7-methyl-2-methylene-l-phenyl-2, 5-dihydro-l//-azepine-3,6-dicarbonitrile (32) to yield the 4-(chloromethylene)-4,5-dihydro-1//-azepine 33 as the final product.127... 

A microwave-assisted variant of the Rosenmund von Braun reaction has also been developed (Scheme 73) [83]. DMF at 200 °C proved not very useful for the cyanodehalogenation of methyl (3R)-6-bromo-5-oxo-2,3-dihydro-5ff-[l,3]thiazolo[3,2-a]pyridine-3-carboxylates since only low yields of the corresponding nitrile were obtained, and there were substantial amoimts of unconverted starting material. Extending the reaction time from 10 to 20 min gave more desired reaction product but also significant amoimts of... 

More versatile seemed the synthesis of 2,3-dihydro-lH-pyridin-4-ones 176, that starts from the acrylic /3-ketoester 174 (Scheme 63). This product, pre-... 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

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