Indol

• 🏭 Supplier — Givaudan

• 📂 CAS N° 120-72-9

• ⚖️ MW — 117.15 g/mol

• 📝 Odor Type — Narcotic (Taught as animal)

• 📈 Odor Strength — High

• 👃🏽 Odor Profile — Naphtha. Pungent, floral, slightly and mothball like with a fecal and animalic musty character.

• ⚗️ Uses — Used in floral composition, especially Jasmin and orange flower. Extremely diffusive and powerful odor, almost tarry-repulsive and choking when concentrated, but in concentrations lower than 0.10. or in compositions, it shows powerful floral notes and pleasant radiation. Good tenacity, in spite of the volatility at room temperature.

What is Indol?

Indole chemistry began to develop with the study of the dye indigo. Indigo can be converted to isatin and then to oxindole. Then, in 1866, Adolf von Baeyer reduced oxindole to indole using zinc dust.[4] In 1869, he proposed a formula for indole.[5]

Certain indole derivatives were important dyestuffs until the end of the 19th century. In the 1930s, interest in indole intensified when it became known that the indole substituent is present in many important alkaloids (e.g., tryptophan and auxins), and it remains an active area of research today.[6]

Indole is an aromatic heterocyclic organic compound with the formula C8H7N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence.[1] 
The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin.[2]

General

Indole is a solid at room temperature. It occurs naturally in human feces and has an intense fecal odor. At very low concentrations, however, it has a flowery smell,[3] and is a constituent of many flower scents (such as orange blossoms) and perfumes. It also occurs in coal tar.

The corresponding substituent is called indolyl.

The name indole is a portmanteau of the words indigo and oleum since indole was first isolated by treatment of the indigo dye with oleum.

Almost insoluble in water, soluble in alcohol, Propylene glycol, and oils. Slightly soluble in hot water. 
By its chemical Nature, lndole may cause some problems in perfumery when incorporated with aldehydes, etc. In some cases, a condensation process leads to a new product, a change in color and viscosity, in other cases the odor and color change is so perceptible that it may be undesirable. The sensitivity of Indole to daylight is well known to the perfumer, and the problems of incorporating lndole in a perfume intended for a white soap has been discussed for decades. Manufacturers of Indole and some perfumers seem to agree, that at least a great part of the problem is due to trace impurities in the Indole, not to lndole itself. It is also beyond doubt that today’s soap cake is far superior to the soap made 10 or 20 years ago, and the wrapping in multiple papers and foil layers was a great step towards safer soap perfuming - and an open door to the use of many materials previously avoided in soaps. 

The ability of indole to discolor aldehydes or to become discolored in their presence is sometimes quite impressive. And since lndole is often shipped in plastic-lined cardboard containers (Indole discolors in presence of Iron), it may permeate the container and its vapors may travel far to cause damage to other materials. Aldehydes and ketones, particularly the crystalline ones, may discolor even when stored at a considerable distance from lndole. Heliotropin and Hydroxyphenyl butanone are typical examples of such sensitive aldehydes and ketones. But with proper packing, and good handling, many of these problems can be overcome. The perfumer will know not to add solid Indole to Heliotropin in the dry state at the beginning of a formula make-up. It is wise to keep the Indole aside and add it when the composition is complete or nearly complete I.e. at the time of the highest dilution of the troublesome components. It is in such cases that a chemistry background comes in handy to the perfumer since many of his “aldehydes” do not even carry a name or a syllabus that indicates that they are aldehydes. 

In the perfume laboratory, it is common practice to have Indole only in the shape of a 10% solution in Diethyl phthalate or other innocuous solvents. The mere presence of Indole crystals even in the most meticulously closed and cleaned glass jar, is a hazard to the odor purity of the perfume laboratory. And the spilling of a few crystal leaflets of Indole may disturb the odor of a perfume laboratory for days or weeks unless they are quantitatively removed.[15]

Production

Indole and its derivatives can also be synthesized by a variety of methods.[7][8][9]

The main industrial routes start from aniline via vapor-phase reaction with ethylene glycol in the presence of catalysts:

In general, reactions are conducted between 200 and 500 °C. Yields can be as high as 60%. Other precursors to indole include formyltoluidine, 2-ethylaniline, and 2-(2-nitrophenyl)ethanol, all of which undergo cyclizations.[10]

Leimgruber–Batcho Indole Synthesis

The Leimgruber–Batcho indole synthesis is an efficient method of synthesizing indole and substituted indoles.[11] Originally disclosed in a patent in 1976, this method is high-yielding and can generate substituted indoles. This method is especially popular in the pharmaceutical industry, where many pharmaceutical drugs are made up of specifically substituted indoles.

Fischer Indole Synthesis

One of the oldest and most reliable methods for synthesizing substituted indoles is the Fischer indole synthesis, developed in 1883 by Emil Fischer. Although the synthesis of indole itself is problematic using the Fischer indole synthesis, it is often used to generate indoles substituted in the 2- and/or 3-positions. Indole can still be synthesized, however, using the Fischer indole synthesis by reacting phenylhydrazine with pyruvic acid followed by decarboxylation of the formed indole-2-carboxylic acid. This has also been accomplished in a one-pot synthesis using microwave irradiation.[12]

Sources:

1.  Lee, Jin-Hyung; Lee, Jintae (2010). "Indole as an intercellular signal in microbial communities". FEMS Microbiology Reviews. 34 (4): 426–44. doi:10.1111/j.1574-6976.2009.00204.x. ISSN 0168-6445. PMID 20070374.

2. Nelson, David L.; Cox, Michael M. (2005), Principles of Biochemistry (4th ed.), New York: W. H. Freeman, ISBN 0-7167-4339-6

3. http://www.leffingwell.com/

4. Baeyer, A. (1866). "Ueber die Reduction aromatischer Verbindungen mittelst Zinkstaub"[On the reduction of aromatic compounds by means of zinc dust]. Annalen der Chemie und Pharmacie. 140 (3): 295–296. doi:10.1002/jlac.18661400306.

5. Baeyer, A.; Emmerling, A. (1869). "Synthese des Indols" [Synthesis of indole]. Berichte der Deutschen Chemischen Gesellschaft. 2: 679–682. doi:10.1002/cber.186900201268.

6. Van Order, R. B.; Lindwall, H. G. (1942). "Indole". Chem. Rev. 30: 69–96. doi:10.1021/cr60095a004.

7. Gribble, G. W. (2000). "Recent developments in indole ring synthesis—methodology and applications". J. Chem. Soc. Perkin Trans. 1 (7): 1045. doi:10.1039/a909834h.

8. Cacchi, S.; Fabrizi, G. (2005). "Synthesis and Functionalization of Indoles Through Palladium-catalyzed Reactions". Chem. Rev. 105 (7): 2873–2920. doi:10.1021/cr040639b. PMID 16011327

9. Humphrey, G. R.; Kuethe, J. T. (2006). "Practical Methodologies for the Synthesis of Indoles". Chem. Rev. 106 (7): 2875–2911. doi:10.1021/cr0505270. PMID 16836303.

10. Collin, Gerd; Höke, Hartmut. "Indole". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a14_167.

11. Indol NSP

12. Bratulescu, George (2008). "A new and efficient one-pot synthesis of indoles". Tetrahedron Letters. 49 (6): 984. doi:10.1016/j.tetlet.2007.12.015.

13. Diels, Otto; Reese, Johannes (1934). "Synthesen in der hydroaromatischen Reihe. XX. Über die Anlagerung von Acetylen-dicarbonsäureester an Hydrazobenzol" [Syntheses in the hydroaromatic series. XX. The addition of acetylene dicarboxylic acid ester to hydrazobenzene]. Justus Liebig's Annalen der Chemie. 511: 168. doi:10.1002/jlac.19345110114.

14. Huntress, Ernest H.; Bornstein, Joseph; Hearon, William M. (1956). "An Extension of the Diels-Reese Reaction". J. Am. Chem. Soc. 78 (10): 2225. doi:10.1021/ja01591a055.

15. S. Arctander, Perfume, and flavor chemicals.

16. essential oils and artificial perfumes, Ernest j parry

17. The chemistry of fragrance

18. National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 798, Indole. Retrieved November 24, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Indole.