A Novel Rearrangement Involving Indole Dimers

Wayland E Noland, Charles F. Hammer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The maleyl and fumaryl derivatives of indole: 2-methylindole dimer (Ib) and the maleyl derivatives of skatole: 2-methylindole dimer (cis-Id) and of indole: 2-phenylindole dimer (cis-Ic) rearrange under alkaline hydrolysis conditions to the corresponding (2-methyl-3-indole) succinic acid (IIb) in the first three cases, or (2-phenyl-3-indole) succinic acid (IIc) in the latter case. The 2-substituent labels the indole nucleus to which migration of the maleyl or fumaryl group has occurred. Besides by means of the rearrangement, (2-phenyl-3-indole) succinic acid (IIc) has been prepared from the reaction of 2-phenylindole with maleic acid. The corresponding anhydride, (2-phenyl-3-indole) succinic anhydride, has been prepared from the diacid by anhydride exchange with acetic anhydride. For rearrangement to occur, the necessity of a hydrogen on nitrogen of the indole nucleus has been demonstrated. This is shown by the fact that the maleyl and fumaryl derivatives of indole: 1,2-dimethylindole dimer (Ie) undergo simple alkaline hydrolysis, without rearrangement, to the dimer and fumaric acid. A mechanism for the rearrangement is proposed in which the maleyl or fumaryl group is transferred intramolecularly through a six-membered spiro ring intermediate from the 1-position of the indoline nucleus to the 3-position of the indole nucleus in the dimer with subsequent depolymerization. The isolation of an isomer of maleyl skatole: 2-methylindole dimer, for which the spiro ring structure of the intermediate has been proposed, lends further support to the proposed intermediate in the mechanism. This isomer rearranges under alkaline hydrolysis conditions to the same product (IIb) as maleyl skatole: 2-methylindole dimer. Some of the limits of the rearrangement are delineated by the facts that, like maleyl and fumaryldiskatole (VII), maleyl indole: 2,5-dimethylpyrrole dimer (VIII) and itaconyldiindole undergo simple amide hydrolysis without rearrangement. Some of the value of the rearrangement, besides in the synthesis of (3-indole) succinic acid (IIa),4 is illustrated by the fact that both the itaconyl (IX) and citraconyl (cis-X) derivatives of indole: 2-methylindole dimer rearrange to the same new diacid, for which the 2-methyl-2-(2-methyl-3-indole) succinic acid structure (XI) is proposed. This diacid is different from another new diacid (XII) derived from hydrolysis of the anhydride adduct of 2-methylindole and itaconic anhydride. Likewise, the anhydrides of the two diacids are different.

Original languageEnglish (US)
Pages (from-to)1536-1542
Number of pages7
JournalJournal of Organic Chemistry
Volume25
Issue number9
DOIs
StatePublished - Jan 1 1960

Fingerprint

Dimers
Anhydrides
Succinic Acid
Skatole
Hydrolysis
Derivatives
indole
Isomers
Depolymerization
Amides
2-methylindole
Labels
Hydrogen
Nitrogen

Cite this

A Novel Rearrangement Involving Indole Dimers. / Noland, Wayland E; Hammer, Charles F.

In: Journal of Organic Chemistry, Vol. 25, No. 9, 01.01.1960, p. 1536-1542.

Research output: Contribution to journalArticle

Noland, Wayland E ; Hammer, Charles F. / A Novel Rearrangement Involving Indole Dimers. In: Journal of Organic Chemistry. 1960 ; Vol. 25, No. 9. pp. 1536-1542.
@article{fdb1970e579b4f60b28a457349ef9b22,
title = "A Novel Rearrangement Involving Indole Dimers",
abstract = "The maleyl and fumaryl derivatives of indole: 2-methylindole dimer (Ib) and the maleyl derivatives of skatole: 2-methylindole dimer (cis-Id) and of indole: 2-phenylindole dimer (cis-Ic) rearrange under alkaline hydrolysis conditions to the corresponding (2-methyl-3-indole) succinic acid (IIb) in the first three cases, or (2-phenyl-3-indole) succinic acid (IIc) in the latter case. The 2-substituent labels the indole nucleus to which migration of the maleyl or fumaryl group has occurred. Besides by means of the rearrangement, (2-phenyl-3-indole) succinic acid (IIc) has been prepared from the reaction of 2-phenylindole with maleic acid. The corresponding anhydride, (2-phenyl-3-indole) succinic anhydride, has been prepared from the diacid by anhydride exchange with acetic anhydride. For rearrangement to occur, the necessity of a hydrogen on nitrogen of the indole nucleus has been demonstrated. This is shown by the fact that the maleyl and fumaryl derivatives of indole: 1,2-dimethylindole dimer (Ie) undergo simple alkaline hydrolysis, without rearrangement, to the dimer and fumaric acid. A mechanism for the rearrangement is proposed in which the maleyl or fumaryl group is transferred intramolecularly through a six-membered spiro ring intermediate from the 1-position of the indoline nucleus to the 3-position of the indole nucleus in the dimer with subsequent depolymerization. The isolation of an isomer of maleyl skatole: 2-methylindole dimer, for which the spiro ring structure of the intermediate has been proposed, lends further support to the proposed intermediate in the mechanism. This isomer rearranges under alkaline hydrolysis conditions to the same product (IIb) as maleyl skatole: 2-methylindole dimer. Some of the limits of the rearrangement are delineated by the facts that, like maleyl and fumaryldiskatole (VII), maleyl indole: 2,5-dimethylpyrrole dimer (VIII) and itaconyldiindole undergo simple amide hydrolysis without rearrangement. Some of the value of the rearrangement, besides in the synthesis of (3-indole) succinic acid (IIa),4 is illustrated by the fact that both the itaconyl (IX) and citraconyl (cis-X) derivatives of indole: 2-methylindole dimer rearrange to the same new diacid, for which the 2-methyl-2-(2-methyl-3-indole) succinic acid structure (XI) is proposed. This diacid is different from another new diacid (XII) derived from hydrolysis of the anhydride adduct of 2-methylindole and itaconic anhydride. Likewise, the anhydrides of the two diacids are different.",
author = "Noland, {Wayland E} and Hammer, {Charles F.}",
year = "1960",
month = "1",
day = "1",
doi = "10.1021/jo01079a019",
language = "English (US)",
volume = "25",
pages = "1536--1542",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - A Novel Rearrangement Involving Indole Dimers

AU - Noland, Wayland E

AU - Hammer, Charles F.

PY - 1960/1/1

Y1 - 1960/1/1

N2 - The maleyl and fumaryl derivatives of indole: 2-methylindole dimer (Ib) and the maleyl derivatives of skatole: 2-methylindole dimer (cis-Id) and of indole: 2-phenylindole dimer (cis-Ic) rearrange under alkaline hydrolysis conditions to the corresponding (2-methyl-3-indole) succinic acid (IIb) in the first three cases, or (2-phenyl-3-indole) succinic acid (IIc) in the latter case. The 2-substituent labels the indole nucleus to which migration of the maleyl or fumaryl group has occurred. Besides by means of the rearrangement, (2-phenyl-3-indole) succinic acid (IIc) has been prepared from the reaction of 2-phenylindole with maleic acid. The corresponding anhydride, (2-phenyl-3-indole) succinic anhydride, has been prepared from the diacid by anhydride exchange with acetic anhydride. For rearrangement to occur, the necessity of a hydrogen on nitrogen of the indole nucleus has been demonstrated. This is shown by the fact that the maleyl and fumaryl derivatives of indole: 1,2-dimethylindole dimer (Ie) undergo simple alkaline hydrolysis, without rearrangement, to the dimer and fumaric acid. A mechanism for the rearrangement is proposed in which the maleyl or fumaryl group is transferred intramolecularly through a six-membered spiro ring intermediate from the 1-position of the indoline nucleus to the 3-position of the indole nucleus in the dimer with subsequent depolymerization. The isolation of an isomer of maleyl skatole: 2-methylindole dimer, for which the spiro ring structure of the intermediate has been proposed, lends further support to the proposed intermediate in the mechanism. This isomer rearranges under alkaline hydrolysis conditions to the same product (IIb) as maleyl skatole: 2-methylindole dimer. Some of the limits of the rearrangement are delineated by the facts that, like maleyl and fumaryldiskatole (VII), maleyl indole: 2,5-dimethylpyrrole dimer (VIII) and itaconyldiindole undergo simple amide hydrolysis without rearrangement. Some of the value of the rearrangement, besides in the synthesis of (3-indole) succinic acid (IIa),4 is illustrated by the fact that both the itaconyl (IX) and citraconyl (cis-X) derivatives of indole: 2-methylindole dimer rearrange to the same new diacid, for which the 2-methyl-2-(2-methyl-3-indole) succinic acid structure (XI) is proposed. This diacid is different from another new diacid (XII) derived from hydrolysis of the anhydride adduct of 2-methylindole and itaconic anhydride. Likewise, the anhydrides of the two diacids are different.

AB - The maleyl and fumaryl derivatives of indole: 2-methylindole dimer (Ib) and the maleyl derivatives of skatole: 2-methylindole dimer (cis-Id) and of indole: 2-phenylindole dimer (cis-Ic) rearrange under alkaline hydrolysis conditions to the corresponding (2-methyl-3-indole) succinic acid (IIb) in the first three cases, or (2-phenyl-3-indole) succinic acid (IIc) in the latter case. The 2-substituent labels the indole nucleus to which migration of the maleyl or fumaryl group has occurred. Besides by means of the rearrangement, (2-phenyl-3-indole) succinic acid (IIc) has been prepared from the reaction of 2-phenylindole with maleic acid. The corresponding anhydride, (2-phenyl-3-indole) succinic anhydride, has been prepared from the diacid by anhydride exchange with acetic anhydride. For rearrangement to occur, the necessity of a hydrogen on nitrogen of the indole nucleus has been demonstrated. This is shown by the fact that the maleyl and fumaryl derivatives of indole: 1,2-dimethylindole dimer (Ie) undergo simple alkaline hydrolysis, without rearrangement, to the dimer and fumaric acid. A mechanism for the rearrangement is proposed in which the maleyl or fumaryl group is transferred intramolecularly through a six-membered spiro ring intermediate from the 1-position of the indoline nucleus to the 3-position of the indole nucleus in the dimer with subsequent depolymerization. The isolation of an isomer of maleyl skatole: 2-methylindole dimer, for which the spiro ring structure of the intermediate has been proposed, lends further support to the proposed intermediate in the mechanism. This isomer rearranges under alkaline hydrolysis conditions to the same product (IIb) as maleyl skatole: 2-methylindole dimer. Some of the limits of the rearrangement are delineated by the facts that, like maleyl and fumaryldiskatole (VII), maleyl indole: 2,5-dimethylpyrrole dimer (VIII) and itaconyldiindole undergo simple amide hydrolysis without rearrangement. Some of the value of the rearrangement, besides in the synthesis of (3-indole) succinic acid (IIa),4 is illustrated by the fact that both the itaconyl (IX) and citraconyl (cis-X) derivatives of indole: 2-methylindole dimer rearrange to the same new diacid, for which the 2-methyl-2-(2-methyl-3-indole) succinic acid structure (XI) is proposed. This diacid is different from another new diacid (XII) derived from hydrolysis of the anhydride adduct of 2-methylindole and itaconic anhydride. Likewise, the anhydrides of the two diacids are different.

UR - http://www.scopus.com/inward/record.url?scp=0007962602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0007962602&partnerID=8YFLogxK

U2 - 10.1021/jo01079a019

DO - 10.1021/jo01079a019

M3 - Article

AN - SCOPUS:0007962602

VL - 25

SP - 1536

EP - 1542

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 9

ER -