Zur Kenntnis der Indolreaktion nach Fischer. II. Thermische und säurekatalysierte Indolisierung von 1′-Alkenyl-2′-methyl-2′-phenylacetohydraziden

✍ Scribed by Peter Schiess; Ebrahim Sendi

• Publisher: John Wiley and Sons
• Year: 1978
• Tongue: German
• Weight: 548 KB
• Volume: 61
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19780610419

✦ Synopsis

On the Fischer‐Indole Reaction. II. Thermal and Acid Catalysed Indolization of 1′‐Alkenyl‐2′‐methyl‐2′‐phenylacetohydrazides

Seven different 1′‐alkenyl‐2′‐methyl‐2′‐phenylacetohydrazides, 6a‐g, have been prepared by treatment of the methylphenylhydrazones 7 of appropriate ketones and aldehydes with acetyl chloride in pyridine. At 170° 6a‐g are transformed into the N‐methylindoles 3a‐g and acetamide in moderate yield. N‐Methylaniline is the other major reaction product indicating that homolytic cleavage of the weak N, N‐bond in 6 is a major primary reaction step. It is likely but not proven that the N‐methylindoles 3 are formed in a reaction sequence initiated by an uncatalysed concerted [3, 3]‐sigmatropic rearrangement.

Upon treatment of 6 with 0.5N dichloroacetic acid in anhydrous acetonitrile at room temperature a quantitative conversion to 3 is observed, interpreted as proceeding by a charge induced [3, 3]‐sigmatropic rearrangement of protonated 6 in the rate determining step. The ketone derivatives 6a‐e (R^1^ = alkyl) react 40‐1000 times faster with acid than the aldehyde derivatives 6f and 6g (R^1^ = H). This is rationalized as a consequence of the increased basicity of 6a‐e relative to 6f and 6g caused by a steric effect.