4-Methylbenzoyl Chloride → 1-Methyl-5-(p-toluoyl)pyrrole-2-acetonitrile

HRID 1973679Notes

Reaction equation

HRID 1973679 reaction equation
ClC1C=CC(C([C:8]2[CH:9]=[C:10]([CH2:14][C:15]#[N:16])[N:11]([CH3:13])[CH:12]=2)=O)=CC=1.[C:19]1([CH3:28])[CH:24]=[CH:23][C:22]([C:25](Cl)=[O:26])=[CH:21][CH:20]=1.CN1C=CC=C1CC#N>>[C:19]1([CH3:28])[CH:24]=[CH:23][C:22]([C:25]([C:12]2[N:11]([CH3:13])[C:10]([CH2:14][C:15]#[N:16])=[CH:9][CH:8]=2)=[O:26])=[CH:21][CH:20]=1

Participants

4

Reactant 3

HCID 134054-Methylbenzoyl ChlorideHCID 905011H-Pyrrole-2-acetonitrile, 1-methyl-HCID 21490353HCID 21490353, compound

Product 1

HCID 111074051-Methyl-5-(p-toluoyl)pyrrole-2-acetonitrileYield 25%

Procedure

The uncatalyzed aroylation process of this invention surprisingly affords better yields of the product, 4-R1 -1-loweralkyl-5-aroylpyrrole-2-acetic acid ester or nitrile. Moreover, when R1 is hydrogen, the usual alpha to beta ratio of product in acylation reactions, that is, the distribution of α-aroylated and β-aroylated isomers, is very greatly shifted in favor of the α-substituted product. For example, in the AlCl3 catalyzed Friedel Crafts reaction of p-chlorobenzoyl chloride with 1-methylpyrrole-2-acetonitrile, a 21% yield of the α-product, 5-(p-chlorobenzoyl)-1-methylpyrrole-2-acetonitrile, is obtained and the ratio of this α-isomer to the corresponding β-isomer, 4-(p-chlorobenzoyl)-1-methylpyrrole-2-acetonitrile, is about 2.5:1; and in the similarly catalyzed reaction of p-toluoyl chloride with 1-methylpyrrole-2-acetonitrile, a 25% yield of the α-product, 5-(p-toluoyl)-1-methylpyrrole-2-acetonitrile, is obtained with an alpha to beta isomer ratio of 3.7:1 [see Carson et al., J. Med. Chem., 14, 646 (1971)]. In contrast, the uncatalyzed reaction of p-chlorobenzoyl chloride with 1-methylpyrrole-2-acetonitrile in refluxing xylene for about 24 hours affords 46% of the corresponding α-product with an α/β ratio of about 440:1; and the uncatalyzed reaction of p-toluoyl chloride with 1-methylpyrrole-2-acetonitrile in refluxing o-dichlorobenzene for about 4 hours affords 55% of the corresponding α-product with an α/β ratio of about 180:1.

Sources & evidence

ORD record
ord-4d32311b213a41a7adbf5912c5f0ac8e
Source dataset
uspto-grants-1976_12
Patent number
US03998844

Reaction notes

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