Skatole, 3-methylindole

Skatole (3-methylindole) readily forms a dimer hydrochloride with HCl in ether or with 15% aqueous HCl, as docs 1,3-dimethyl-indole. 3-n-Propylindole is also readily dimerized in dry ether/HCl/ ... 

Indole derivatives were studied by Philbrook et al. in 1965, showing the CL emission produced in the presence of oxygen and under strong alkaline conditions [97], following the reaction scheme depicted in Figure 10 for skatole (3-methylindole). 

A number of other indole derivatives have also been observed to yield CL subsequent to oxidation. Among these is skatole (3-methylindole), which emits light after oxidation by 02 under strongly alkaline conditions [9],... 

Tryptophan can be converted to indolepyruvic acid either by oxidative deamination or by transamination (e.g., 739, 912) and the indolepyruvic acid can give rise to indoleacetic acid. The fate of indoleacetic acid formed by the bacterial flora of the mammalian gut is discussed below. Bacterial indolelactic acid (e.g., 757) is presumably derived from indolepyruvic acid, but indolelactic acid excreted by mammals (e.g. 17) may be of true mammalian rather than bacterial origin. Indolepropionic acid can also be formed by bacteria (e.g., 412, 633), but further metabolism in mammals of any indolepropionic acid formed in the gut is still obscure (904). Skatole (3-methylindole) has long been known as a product of bacterial decomposition of protein and is formed from tryptophan not only by the bacterial flora of the gut but also in putrefying secretions, e.g., sputum (756). It may well arise by decarboxylation of indoleacetic acid. 

Indican was early considered to be a normal constituent of human urine (413), but this was disputed by later workers, probably owing to the inadequate sensitivity of the tests employed. Its normal occurrence is now established (87, 175). Indole produces nausea, headache, and other unpleasant symptoms (649), whereas indican is pharmacologically almost inactive (435). Indican formation is therefore a true detoxication, but in man only about 30% to 50% of ingested indole is converted to indican (87, 649). A good deal of the indole produced in the gut appears in the feces, indole and the related skatole (3-methylindole) being largely responsible for the typical fecal smell. 

Oral tryptophan causes marked pulmonary edema and emphysema. This appears to be due to the bacterial conversion of tryptophan to skatole (3-methylindole), which causes the same type of lung lesion.33... 

Indole and the simple alkyl-indoles are colourless crystalline solids with a range of odours from naphthalene-like, in the case of indole itself, to faecal, in the case of skatole (3-methylindole). Many simple indoles are available commercially and all of these are produced by synthesis indole, for example, is made by the high-temperature vapour-phase cyclising dehydrogenation of 2-ethylaniline. Most indoles are quite stable in air with the exception of those which carry a simple alkyl group at C-2 2-methylindole autoxidises easily, even in a dark brown bottle. 

Other well-known indoles that have various natural sources are skatole (3-methylindole) (2), serotonin (3), L-tryptophan (4), tryptamine (5), the plant growth hormones 3-indoleacetic acid (6) and 4-chloro-3-indoleacetic acid (7) [19], the mushroom hallucinogen psilocin (8), and the indole-derived ancient dyes indigo (9) [20] and Tyrian Purple (10) [19] (Scheme 1). 

Microorganisms (including intestinal bacteria) break down the side chains of tryptophan. In the process there may be formed indolepyruvate, indoleacetate, skatole (methylindole), and indole itself. Indoleacetate is a plant hormone auxin] Chapt. XX-15). 

Methylindole (skatole) [83-34-1] M 131.2, m 95 , pK -4.55 (C-3-protonation, aq H2SO4). Crystd from benzene. Purified by zone melting. 

Methylindole has also been prepared by lithium aluminum hydride reduction of 1-methylindoxyl. Compounds giving rise to NH absorption in the infrared (indole, skatole) can be completely removed by refluxing the crude 1-methylindole over sodium for 2 days and then distilling the unreacted 1-methylindole from the sodio derivatives and tarry decomposition products. 

Acetyl-3-methyIindoIe (117) was obtained when the. skatole Grignard reagent was treated with acetyl chloride at 100° in the absence of Solvent, but l-acetyl-3-methylindole (118) was obtained when the... 

Mingoia reported that 2-chloroacetyl-3-methylindole (139) was obtained by the action of chloroacetyl chloride on the skatole Grignard reagent. ... 

In 1912 Oddo reported the results of an investigation of the products obtained on carbonation of both the 2- and 3-methylindole Grignard reagents. In the former case the relatively unstable l-carboxy-2-methylindole (377) was the main product obtained when the reaction was carried out at temperatures up to 35° however, at 110° the isomeric 3-carboxy-2-methylindole (378) was the major product formed. According to Oddo l-carboxy-3-methylindole (379) is more stable than the corresponding 2-methyl compound (i.e., 377) and can be obtained by carbonation of the skatole Grignard reagent at 100°. ... 

Ingraffia studied the oxidation of the Grignard reagents derived from indole, skatole, and 2-methylindole with hydrogen peroxide and... 

Methylindole is, however, incorporated into mixed dimers and trimers. It thus reacts with indole and with skatole to form mixed dimers, and 2 moles react with 1 mole of indole for form a mixed trimcr. Likewise indole forms a dimer with 1,2-dimethylindole, 2-phenylindole, and even with 2,5-dimethylpyrrole, ... 

Again based on the failure of 2-methylindole to form a dimer, Schmitz-DuMont proposed structure (29) for skatole dimer. Structure (30) was, however, shown to be the correct one independently in three... 

The dimerization of skatole proceeds in an entirely analogous manner, cation (44) now being the electrophilic reagent. This is sufficiently reactive to effect substitution at the a-position of a neutral skatole molecule. Attack by the less hindered side of cation (44) will be favored, leading to the stereochemistry shown in structure (30). The failure of 2-methylindole to dimerize is paralleled by the failure of 2-methylpyrrole dimer to react with a further molecule of 2-methylpyrrole. The main reason is almost certainly again the reduction in the electrophilic character of the immonium carbon by... 

SYNS 3-METHYLINDOLE 3-METHYL-lH-INDOLE 3-MI SCATOLE SKATOL SKATOLE... 

Methylindole. Also known as scatol or skatole, it is a solid with a foul fecal odor. It is a skin and eye irritant (MSDS, 2005c). 

Other characteristic colors are produced by thymol and 3-methylindole (skatole). The red color formed with thymol, first mentioned by Baldeon, is read at 505 nm, and the purple color given by the skatole reagent is extracted with chloroform and measured at 510 nm. This is time-consuming, but it stops the reaction and permits readings to be made after any desired time-interval. 

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