[108-75-8]  · C8H11N  · 2,4,6-Collidine  · (MW 121.18)

(most useful in dehydrohalogenation reactions;1 used for basic properties as reaction solvent or additive)

Alternate Name: 2,4,6-trimethylpyridine.

Physical Data: bp 170 °C; mp -44.5 °C; d 0.913 g cm-3 at 20 °C. Isomers of the title reagent include 2,3,4-collidine ([2233-29-6]; bp 192-193 °C), 2,3,5-collidine ([695-98-7]; bp 182-183 °C/739 mmHg), 2,3,6-collidine ([1462-84-6]; bp 176-178 °C), 2,4,5-collidine ([1122-39-0]; bp 165-168 °C), and 3,4,5-collidine ([20579-43-5]; bp 205-207 °C).2-4

Solubility: sol 3.5 g/100 mL H2O (20 °C) and 20.8 g/100 mL H2O (6 °C); miscible with ether; sol methanol, ethanol, chloroform, benzene, toluene, dilute acids.3

Form Supplied in: liquid.

Analysis of Reagent Purity: GLC.

Purification: by distillation.

Handling, Storage, and Precautions: protect from light; moisture sensitive; incompatible with strong oxidizing agents.5

Dehydrohalogenation Reactions.

Numerous examples in the literature describe the utility of collidines to aid in dehydrohalogenation reactions. One example (eq 1) is the synthesis of 2-methyl-2-cyclohexenone (2) from 2-chloro-2-methylcyclohexanone (1).6 Another example involves the dehydrobromination of tetrahydrofuran (3) to diene (4) en route from linalool to karahanaenone (62%, overall, eq 2).7 Similarly, dehydrobromination of stigmasteryl acetate (5) affords 7-dehydrostigmasteryl acetate (6) in a refluxing mixture of collidine and mesitylene (eq 3).1

A key step in a synthesis of pyridocarbazoles used collidine in THF for a dehydrochlorination. A hindered base such as collidine was required to avoid cleavage of the lactone ring, the preferred reaction using a base such as N,N-dimethylaniline (eq 4).8

2,4,6-Collidine is used as solvent in the preparation of 2-benzylcyclopentanone (8) from 2-benzyl-2-methoxycarbonylcyclopentane (7) (eq 5).9

Cleavage of alkyl aryl ethers (72-76%) occurs in high yield with Lithium Iodide with 2,4,6-collidine as solvent.10 In the absence of a solvent, high reaction temperatures are required.

Collidine as a Base Catalyst.

Collidine is useful as a base in a variety of reactions. Sometimes it doubles as reaction base and solvent. A mixture of monobromo isomers is obtained in very high yield when 1-methylcyclopropyl-3-methyl-3-butenylcarbinol (9) is treated with Phosphorus(III) Bromide and collidine (eq 6).11 The bromo compounds shown underwent further reaction with Zinc Bromide to form trans-1-bromo-3,7-dimethylocta-3,7-diene in 85-90% yield.

Collidine is effective as a proton scavenger in the Koenigs-Knorr synthesis of disaccharide glycosides. Silver(I) Trifluoromethanesulfonate and collidine are paired as a useful promoter of glycosylation reactions of alcohols with glycosyl halides. For example, the reaction of hepta-O-acetyl-a-D-cellobiosyl bromide (10) with 8-ethoxycarbonyloctanol (11) in the presence of silver triflate and collidine afforded a 78% yield of the corresponding 1,2-orthoacetate derivative (12) (eq 7).12 When a similar reaction was carried out with N,N,N,N-tetramethylurea in place of collidine, a different reaction path was followed to give isomeric 1,2-trans-glycosides.

Collidine is also used as the base for glycosidation reactions promoted by Tin(II) Trifluoromethanesulfonate. Starting with glucose derivative (13) and protected sugar derivatives, 1,2-trans-b-D-disaccharides have been prepared by this method (eq 8)13

Collidine behaves as a nucleophilic catalyst in reactions such as the hydrolysis of picryl chloride. The reaction proceeds by formation of intermediate N-picryl-2,4,6-trimethylpyridinium ion (14) (eq 9).14

Collidine acts as a sterically hindered base in tritylation reactions of very weakly acidic compounds. The tritylation reaction proceeds in high yield for both acetone and acetonitrile, which serve as both reactant and solvent in the syntheses of 1,1,1-triphenyl-3-butanone (15) and 1,1,1-triphenylpropionitrile (16), respectively (eqs 10 and 11).15 This tritylation is a general reaction, applicable to more strongly acidic compounds such as diethyl malonate and nitromethane. In the nitromethane reaction, a low yield of the desired product is obtained due to side reactions.

1. Kircher, H. W.; Rosenstein, F. U. JOC 1973, 38, 2259.
2. Goe, G. L. In Kirk-Othmer Encyclopedia of Chemical Technology; Wiley: New York, 1982; Vol. 19, p 454.
3. The Merck Index, 11th ed.; Budavari, S., Ed.; Merck: Rahway, NJ, 1989; p 1529.
4. Dictionary of Organic Compounds, 5th ed.; Buckingham, J., Ed.; Chapman & Hall: London, 1982; p 5592.
5. The Sigma Aldrich Library of Regulatory & Safety Data; Aldrich: Milwaukee, WI, 1993; Vol. 2, p 2503.
6. Warnhoff, E. W.; Martin, D. G.; Johnson, W. S. OSC 1963, 4, 162.
7. Demole, E.; Enggist, P. HCA 1971, 54, 456.
8. Narasimhan, N. S.; Gokhale, S. M. CC 1985, 86.
9. Elsinger, F. OSC 1973, 5, 76.
10. Harrison, I. T. CC 1969, 616.
11. Brady, S. F.; Ilton, M. A.; Johnson, W. S. JACS 1968, 90, 2882.
12. Banoub, J.; Bundle, D. R. CJC 1979, 57, 2091.
13. Lubineau, A.; Malleron, A. TL 1985, 26, 1713.
14. de Rossi, R. H.; de Vargas, E. B. JOC 1979, 44, 4100.
15. Bidan, G.; Cauquis, G.; Genies, M. T 1979, 35, 177.

Angela R. Sherman

Reilly Industries, Indianapolis, IN, USA

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