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Org. Synth. 1950, 30, 41
DOI: 10.15227/orgsyn.030.0041
5-ETHYL-2-METHYLPYRIDINE
[2-Picoline, 5-ethyl-]
Submitted by Robert L. Frank, Frederick J. Pilgrim, and Edward F. Riener1,2.
Checked by R. S. Schreiber and T. L. Alderson.
1. Procedure
Two hundred and sixty-seven grams (296 ml., 4.38 moles) of 28% aqueous ammonium hydroxide, 207.5 g. (209 ml., 1.57 moles) of paraldehyde, and 5.0 g. (0.065 mole) of ammonium acetate are heated to 230° with continuous agitation in a 2-l. steel reaction vessel (Note 1), and the temperature is maintained at 230° for 1 hour (Note 2). The autoclave is then allowed to cool, and the two layers of the reaction mixture are separated (Note 3). To the non-aqueous layer is added 60 ml. of chloroform, causing separation of water which is combined with the aqueous layer. The aqueous layer is extracted with three 50-ml. portions of chloroform, and the extracts are combined with the main portion of the chloroform solution. After removal of the chloroform by distillation at atmospheric pressure, fractional distillation under reduced pressure through a 30-cm. Fenske-type column3 gives a fore-run of water, paraldehyde, and α-picoline, b.p. 40–60°/17 mm., followed by 72–76 g. (50–53%) of 5-ethyl-2-methylpyridine, b.p. 65–66°/17 mm.; nD20 1.4971 (Note 4).
2. Notes
1. A steel reaction vessel of the type used for high-pressure catalytic hydrogenations is satisfactory. The pressure of the reaction mixture ranges from 800 to 3000 lb. A larger volume of reactants should not be used in a 2-l. reaction vessel.
2. The reaction is exothermic and in some reaction vessels may cause the temperature to rise above 230° for a short period. This has no apparent effect on the yield of product. The temperature measured is that of a thermocouple inserted in a well in the cover of the autoclave and corresponds to about 250° if the thermocouple is in the wall of the autoclave.
3. The mixture contains a small amount of solid material, apparently due to slight corrosion of the steel reaction vessel. If the solid causes the formation of an emulsion, it can be removed by filtration.
4. The yield may be increased to 60–70% by use of an 8:1 molar ratio of ammonium hydroxide to paraldehyde, but this is generally inconvenient because of the greatly increased volume of the reaction mixture.
3. Discussion
5-Ethyl-2-methylpyridine (also known as "aldehyde-collidine") has been prepared by heating aldehyde-ammonia;4 aldehyde-ammonia and acetaldehyde5,6,7 or paraldehyde;7,8,9 aldol-ammonia and ammonia;10 paraldehyde and ammonia;11,12,13 acetamide,14 or acetamide and phosphorus pentoxide15 ethylene glycol and ammonium chloride;16 ethylidene chloride17,18 or bromide19 and amonia; ethylidene chloride and acetamide, ethylamine, or n-amylamine;16 crotonic acid and a calcium chloride-ammonia complex;20 and by passage of acetylene21 or acetaldehyde22 and ammonia over alumina and other catalysts.
A study has been made of catalysts for the present reaction,23 and a mechanism for the synthesis of pyridine and its derivatives by the Beyer-Chichibabin method has been published.24

References and Notes
  1. University of Illinois, Urbana, Illinois.
  2. Work done under contract with the Office of Rubber Reserve.
  3. Fenske, Tongberg, and Quiggle, Ind. Eng. Chem., 26, 1169 (1934).
  4. Ador and Baeyer, Ann., 155, 297 (1870).
  5. Dürkopf and Schlaugk, Ber., 21, 294 (1888).
  6. Dürkopf, Ber., 20, 444 (1887).
  7. Tschitschibabin and Oparina, J. prakt. Chem., [2] 107, 138 (1924).
  8. Plath, Ber., 21, 3086 (1888).
  9. Ladenburg, Ann., 247, 42 (1888).
  10. Wurtz, Ber., 8, 1196 (1875).
  11. Farbwerke vorm. Meister, Lucius and Brüning, Brit. pat. 146,869 [C. A., 14, 3675 (1920)]; Austrian pat. 81,299 [Chem. Zentr., 92 II, 35 (1921)]; French pat. 521,891 [Chem. Zentr., 92 IV, 805 (1921)].
  12. Graf and Langer, J. prakt. Chem., 150, 153 (1938); Frank and Seven, J. Am. Chem. Soc., 71, 2629 (1949).
  13. Mahan (to Phillips Petroleum Co.), U. S. pat. 2,877,228 [C. A., 53, 13182 (1959)]; Farberov, Ustavshchikov, Kut'in, Vernova, and Yarosh, Izvest. Vysshykh Ucheb. Zavedenii, Khim. i Khim. Tekhnol., 1958, No. 5, 92 [C. A., 53, 11364 (1959)]; Kudo, Repts. Statist. Appl. Research, Union Japan. Scientists and Engrs., 6, No. 1, 13 (1959) [C. A., 53, 21934 (1959)]; Frank, Blegen, Dearborn, Myers, and Woodward, J. Am. Chem. Soc., 68, 1368 (1946).
  14. Pictet and Stehelin, Compt. rend., 162, 877 (1916).
  15. Hesekiel, Ber., 18, 3095 (1885).
  16. Hofmann, Ber., 17, 1905 (1884).
  17. Kraemer, Ber., 3, 262 (1870).
  18. Dürkopf, Ber., 18, 920 (1885).
  19. Tawildarow, Ann., 176, 15 (1875).
  20. Fichter and Labhardt, Ber., 42, 4714 (1909).
  21. Tschitschibabin and Moschkin, J. Russ. Phys. Chem. Soc., 54, 611 (1922–1923); J. prakt. Chem., [2] 107, 109 (1924); Murahashi and Otuka, Mem. Inst. Sci. Ind. Research, Osaka Univ., 7, 121 (1950) [C. A., 45, 9052 (1951)].
  22. Tschitschibabin, Moschkin, and Tjaschelowa, J. prakt. Chem., [2] 107, 132 (1924).
  23. Arai, Osuka, Tanabe, Teramoto, and Ichikizaki, J. Chem. Soc. Japan, Ind. Chem. Sect., 57, 495 (1954) [C. A., 49, 15892 (1955)].
  24. Herzenberg and Boccato, Chim. & ind. (Paris), 80, 248 (1958).

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

alumina

aldehyde-ammonia

aldol-ammonia

amonia

calcium chloride-ammonia complex

acetaldehyde (75-07-0)

acetylene (74-86-2)

Acetamide (60-35-5)

ammonia (7664-41-7)

ammonium acetate (631-61-8)

ammonium chloride (12125-02-9)

chloroform (67-66-3)

pyridine (110-86-1)

ethylene glycol (107-21-1)

ammonium hydroxide (1336-21-6)

crotonic acid (3724-65-0)

α-picoline (109-06-8)

ethylamine (75-04-7)

5-Ethyl-2-methylpyridine,
2-Picoline, 5-ethyl- (104-90-5)

ethylidene chloride (75-34-3)

phosphorus pentoxide (1314-56-3)

n-amylamine (110-58-7)

paraldehyde (123-53-7)