An Extension of the Diels-Reese Reaction¹

Abstract

The adduct from dimethyl acetylenedicarboxylate and 4,4'-dimethylhydrazobenzene yielded no indole derivative under the conditions of the Diels-Reese reaction but did give, by heating in a-picoline, 2-hydroxy-3-(p-toluino)-4-carbometh~x~-~-methylquinoline.The adduct from dimethyl acetylenedlcarboxylate and 4,4'-dichlorohydrazobenzene gave both dimethyl 5-chloroindole-2,3-dicarboxylate and Z-hydroxy-3-(P~h~orani~ino)-4-carbomethoxy-6-chloroquinoline under suitable conditions. The latter was degraded t o 2,3-dihydroxy-6-chloroquinoline. The adduct from dimethyl acetylenedicarboxylate and 4-acetoxyhydrazobenzene did not yield any indole derivative but did produce, by heating in a-picoline, 2-hydroxy-3-anilino-4-carbomethoxy-6-acetoxyqu~nol~ne. The latter was degraded t o the hitherto unknown 2,3,6-trihydroxyquinoline which was also prepared by an independent synthesis.The latter was degraded t o 2,3-dihydroxy-6-methylquinoline.Diels and Reese3 found that dimethyl acetylenedicarboxylate and hydrazobenzene react in warm methanol to form a 1: 1 adduct which could be transformed under suitable conditions to three types of heterocyclic compounds. In glacial acetic acid, the adduct yielded 1,2-diphenyl-3-carbomethoxy-5-pyrazolone (111), in xylene it gave dimethyl indole-2,3-dicarboxylate (IV, R = R1 = H) while in pyridine it afforded 2-hydroxy-3-anilino-4-carbomethoxyquinoline (V, R = R' = H). V (R = R' = H) was degraded4 to 2,3-dihydroquinoline (VII, R = R1 = H) by decarboxylation of the derived acid (VI, R = R1 = H) followed by hydrolysis of the anilino group.We have completely substantiated this remarkable series of reactions reported by Diels and Reese and have now extended the above reactions to three substituted hydrazobenzenes. The formation of the corresponding pyrazolones, however, has not been studied since they are readily prepared by simpler procedures. The hydrazobenzenes used were the 4,4'-dimethyl-, the 4,4'-dichloro-and the 4-acetoxy-. All formed adducts readily with dimethyl acetylenedicarboxylate in good yield.The adduct from 4,4'-dimethylhydrazobenzene when heated in a-picoline gave the expected 2-hydroxy -3 -( p -to1uino)-4 -carbomethoxy-6-methylquinoline (V, R = R1 = CH,) which on saponification gave the free acid (VI, R = R1 = CH3). VI (R = R' = CH3) on hydrolysis and decarboxylation produced 2,3-dihydroxy-6-methylquinoline (VII, R = CH3). This same adduct when heated in xylene did not give the corresponding indole, however, but only the quinoline derivative listed above V (R = R 1 = CH3).The adduct from 4,4'-dichlorohydrazobenzene gave the expected products. In a-picoline, it yielded 2-hydroxy-3-(p-chloroanilino) -4-carbomethoxy-6-chloroquinoline (V, R = R' = Cl) which was saponified to the free acid (VI, R = R' = Cl), which, in turn, was hydrolyzed and decarboxylated with hydriodic acid (neither hydrochloric nor hydrobromic acids were effective) to the corresponding 2,3-dihydroxy-6-chloroquinoline (VII, R = Cl). The adduct readily gave dimethyl 5-chloroindole-2,3-dicarboxylate (IV, R = C1) when heat...

Synthesis of the Indole Ring

“…The reactions H81 -> H83, H84 -> H85, and H86 -> H87 were reported some years ago by Huntress and co-workers (110)(111)(112). The mechanistic interpretation of these reactions is clouded by some uncertainty about the structures of some of the initial adducts which are formed in the reactions.…”

Synthesis of 5,7‐Dihydrodibenzo[b,f][1,7]naphthyridine‐6,12‐dione, an Unexpected Isolate from Isatis tintoria

“…Dimethyl acetylenedicarboxylate (¼ dimethyl but-2-ynedioate) was purchased from Sigma Aldrich. A limited number of 3-(arylamino)-1,2-dihydro-2-oxoquinoline-4-carboxylic acid methyl esters could be prepared according to a known procedure [15] with freshly prepared 1,2-diarylhydrazines. Shortly, the hydrazine and dimethyl (or diethyl) acetylenedicarboxylate were used in equimolar amounts and boiled in MeOH.…”

“…2875m, 1687s, 1658vs, 1565s, 1523s, 1472w, 1405w, 1368w, 1313w, 1258m, 1236w, 1187w, 945w, 898w, 859w, 809s, 774w, 684w, 3024m, 2924m, 1670vs, 1602vs, 1558s, 1537s, 1504s, 1453w, 1421m, 1386m, 1342w, 1322w, 1291m, 1259w, 1209w, 1195w, 1160w, 1039w, 993w, 903w, 874w, 822m, 770m, 710m, 670w 3341s, 2932m, 2833m, 1675s, 1660 (sh), 1615s, 1588m, 1555w, 1512vs, 1454w, 1411w, 1366m, 1321m, 1295s, 1245s, 1219s, 1190m, 1169m, 1129w, 1035m, 904w, 842m, 826w, 808w, 781w, 729w, 710w, 678w, 610m, 3-[(3,4-Dimethylphenyl)amino]-1,2-dihydro-6,7-dimethyl-2-oxoquinoline-4-carboxylic Acid (9e). Following the procedure reported in [15], a bright yellow powder was obtained in 78% yield, consisting of 3-[(3,4-dimethylphenyl)amino]-1,2-dihydro-6,7-dimethyl-2-oxoquinoline-4-carboxylic acid methyl ester and ca. 18% of 3-[(3,4-dimethylphenyl)amino]-2-hydroxy-5,6-dimethylquinoline-4-carboxylic acid methyl ester.…”

“…The use of POCl 3 also promoted cyclization but yielded the chloro derivatives 10a -10c (Scheme), as expected. Access to the 3-(arylamino)-2-hydroxyquinoline-4-carboxylic acids 9a -9d was easy; they are the products of a Fischer-type rearrangement of diesters 11, which are adducts of symmetric 1,2-diarylhydrazines with acetylenedicarboxylic acid dimethyl ester (¼ dimethyl but-2-ynedioate) [15]. With nonsymmetric 1,2-diarylhydrazines, this reaction gave mixtures whose purification was difficult.…”

Synthesis of the Indole Nucleus

“…243). If 2 equiv of oxidant are used, only 759 is obtained .583 K3Fe(CN), NatiC03 OH N I 759 8, 758 Harley-Mason's work on the oxidation of 3,4-dihydroxyphenylalanines and 2,5-dihydroxyphenylalanines has led to the suggestion of a possible route to the biogenesis of hydroxyindoles from tyrosine (682) 526. 5w4 This is shown in Scheme 73.…”