A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Page
GO
GO
?
^
Top
Org. Synth. 1942, 22, 98
DOI: 10.15227/orgsyn.022.0098
2-PHENYLINDOLE
[Indole, 2-phenyl-]
Submitted by R. L. Shriner, W. C. Ashley, and E. Welch.
Checked by Homer Adkins, Alan K. Roebuck, and Harry Coonradt.
1. Procedure
In a tall 1-l. beaker is placed an intimate mixture of 53 g. (0.25 mole) of freshly prepared acetophenone phenylhydrazone (Note 1) and 250 g. of powdered anhydrous zinc chloride (Note 2). The beaker is immersed in an oil bath at 170°, and the mixture is stirred vigorously by hand. The mass becomes liquid after 3–4 minutes, and evolution of white fumes begins. The beaker is removed from the bath, and the mixture is stirred for 5 minutes. In order to prevent solidification to a hard mass, 200 g. of clean sand is thoroughly stirred into the reaction mixture. The zinc chloride is dissolved by digesting the mixture overnight on the steam cone with 800 ml. of water and 25 ml. of concentrated hydrochloric acid (sp. gr. about 1.2). The sand and crude 2-phenylindole are removed by filtration, and the solids are boiled with 600 ml. of 95% ethanol. The hot mixture is decolorized with Norit and filtered through a hot 10-cm. Büchner funnel, and the sand and Norit are washed with 75 ml. of hot ethanol. After the combined filtrates are cooled to room temperature, the 2-phenylindole is collected on a 10-cm. Büchner funnel and washed three times with small amounts (15–20 ml.) of cold ethanol. The first crop is quite pure; after drying in a vacuum desiccator over calcium chloride it weighs 30–33 g. and melts at 188–189° (cor.) (Note 3) and (Note 4).
A little Norit is added to the combined filtrate and washings, which are then concentrated to a volume of 200 ml. and filtered. The filtrate, on cooling, deposits a second crop of 5–6 g. (Note 5) of impure product, which melts at 186–188°. The total yield of 2-phenylindole is 35–39 g. (72–80%).
2. Notes
1. Acetophenone phenylhydrazone is prepared 1 by warming a mixture of 40 g. (0.33 mole) of acetophenone and 36 g. (0.33 mole) of phenylhydrazine on the steam cone for 1 hour. The hot mixture is dissolved in 80 ml. of 95% ethanol, and crystallization is induced by agitation. The mixture is then cooled in an ice bath, and the product is removed and washed with 25 ml. of ethanol. There is obtained 54–57 g. of white product. A second crop of 4–10 g. is obtained by concentrating the combined filtrate and washings. The combined solids are dried under reduced pressure, over calcium chloride, for 30 minutes. The total yield of acetophenone phenylhydrazone, m.p. 105–106°, is 61–64 g. (87–91%).
2. It has been reported2 that such a large amount of zinc chloride is not necessary, but the submitters found that equal parts of acetophenone phenylhydrazone and zinc chloride gave lower yields.
3. Using 3.2 times the quantities specified above, except that no sand was added in separating the product, the checkers have obtained yields of 75–80% of 2-phenylindole.
4. While drying, the surface of the product becomes very light green.
5. The filtrate still contains some 2-phenylindole, but great difficulty is encountered in trying to purify the crude material.
3. Discussion
2-Phenylindole has been prepared by heating benzoyl-o-toluidine in an atmosphere of hydrogen,3 the reaction being improved by the use of sodium amyloxide as the condensing agent; by heating phenylacetaldehydephenylhydrazone with 5 parts of anhydrous zinc chloride;4 by warming phenacyl bromide5,6 or N-phenacylaniline with aniline,7 aniline hydrochloride, or zinc chloride;8 by elimination of water from o-aminodesoxybenzoin,9 prepared in turn from o-nitrodesoxybenzoin; by dehydration of benzal-o-toluidine;10 by the action of anhydrous zinc chloride11 or boron trifluoride12 upon the phenylhydrazone of acetophenone; by the action of potassium amide and potassium nitrate upon 2-phenyl-4-quinolinecarboxylic acid.13 N15-2-Phenylindole has been prepared from the α-N15-phenylhydrazone of acetophenone.14

References and Notes
  1. Reisenegger, Ber., 16, 662 (1883).
  2. Arbuzov and Tichvinshi, J. Russ. Phys. Chem. Soc., 45, 70 (1913); [C. A., 7, 2225, 3599 (1913)].
  3. Madelung, Ber., 45, 1131 (1912).
  4. Fischer and Schmitt, Ber., 21, 1072 (1888).
  5. Mohlau, Ber., 15, 2480 (1882).
  6. Bischler, Ber., 25, 2860 (1892).
  7. Mentzer, Molho, and Berguer, Bull. soc. chim. France, 1950, 555.
  8. Verkade and Janetsky, Rec. trav. chim., 62, 763 (1943).
  9. Pictet, Ber., 19, 1064 (1886).
  10. Etard, Compt. rend., 95, 730 (1882).
  11. Fischer, Ann., 236, 133 (1886).
  12. Snyder and Smith, J. Am. Chem. Soc., 65, 2452 (1943).
  13. White, Doctorate thesis, Stanford University, 1940; White and Bergstrom, J. Org. Chem., 7, 497 (1942).
  14. Allen and Wilson, J. Am. Chem. Soc., 65, 611 (1943).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

sodium amyloxide

o-aminodesoxybenzoin

o-nitrodesoxybenzoin

phenylhydrazone of acetophenone

N15-2-Phenylindole

α-N15-phenylhydrazone of acetophenone

ethanol (64-17-5)

calcium chloride (10043-52-4)

hydrochloric acid (7647-01-0)

aniline (62-53-3)

hydrogen (1333-74-0)

aniline hydrochloride (142-04-1)

Phenylhydrazine (100-63-0)

Acetophenone (98-86-2)

Norit (7782-42-5)

zinc chloride (7646-85-7)

potassium nitrate (7757-79-1)

boron trifluoride (7637-07-2)

Phenacyl bromide (70-11-1)

acetophenone phenylhydrazone

potassium amide

2-Phenylindole,
Indole, 2-phenyl- (948-65-2)

phenylacetaldehydephenylhydrazone

N-phenacylaniline

2-phenyl-4-quinolinecarboxylic acid (132-60-5)

benzoyl-o-toluidine

benzal-o-toluidine