[91-22-5]  · C8H7N  · Quinoline  · (MW 129.16)

(useful as a base, solvent and/or catalyst, especially for decarboxylation reactions1 and the Rosenmund reaction2,3)

Physical Data: mp -15 °C; bp 237.6 °C;4 steam volatile; d 1.0858 g cm-3 at 30 °C; pKa 9.5.5

Solubility: sol ethanol, ethyl ether, acetone, carbon disulfide; more readily sol hot water than cold water; quinoline dissolves sulfur, phosphorus, and arsenic trioxide.

Form Supplied in: colorless liquid.

Analysis of Reagent Purity: GLC.

Purification: distillation.

Handling, Storage, and Precautions: very hygroscopic; darkens on storage in light; package with protection from light and moisture; LD50 rat (oral) 460 mg kg-1; incompatible with strong oxidizing agents and strong acids.5,6

Dehydrohalogenation Reactions.

Quinoline is sometimes used as a base or solvent for dehydrohalogenation reactions because of its basic properties. A wide variety of substrates, ranging from very simple to quite complex compounds, have been effectively dehydrohalogenated with quinoline. For example, 3-bromo-3-methyl-2-butanone (1) underwent reaction with quinoline to give a mixture of products, 3-methyl-2-butanone (2) and 2-methyl-1-buten-3-one (3) (eq 1).7

Trans-3-penten-2-one (5) has been prepared from 4-chloropentan-2-one (4) using quinoline as the acid scavenger (eq 2).8

Dehydrochlorination of 2-oxa-7,7-dichloronorcarane (6) in quinoline gives an 83% yield of 2,3-dihydro-6-chlorooxepine (7) (eq 3).9

Similarly, when 7,7-dibromonorcarane (8) is treated with quinoline, by manipulation of reaction conditions the bromocyclohepta-1,3-diene derivatives can be isolated or total dehydrobromination to 1,3,5-Cycloheptatriene (9) can be effected (eq 4).10

Selective dehydrobromination of (a-bromovinyl)chlorosilanes can be carried out in quinoline, affording fair to good yields of the corresponding ethynylchlorosilanes (eq 5).11

Decarboxylation Reactions.

Taking advantage of its basic properties, quinoline is generally useful as a solvent for decarboxylation reactions. It is especially suitable because its relatively high boiling point facilitates the decarboxylation. Examples include the decarboxylation of 3-methyl-2-furoic acid (10) to 3-methylfuran (11) (eq 6),12 m-nitrocinnamic acid (12) to m-nitrostyrene (13) (eq 7),1 and a-phenylcinnamic acid (14) to cis-stilbene (15) (eq 8).13 Copper catalysts such as Copper or Copper Chromite are used to effect the decarboxylations.

Preparation of Isothiocyanates.

Ethoxycarbonyl Isothiocyanate (18), useful as a synthetic reagent for heterocyclic syntheses,14 can be prepared in excellent yield from the reaction of Ethyl Chloroformate (16) with Sodium Thiocyanate (17) using quinoline as a base catalyst (eq 9).15 Only trace amounts of the isomeric thiocyanates are formed in the reaction. In the absence of the base catalyst, only a moderate (65%) yield of the desired product is obtained, along with significant (10%) contamination by the isomeric ethoxycarbonyl thiocyanate. Pyridine can also be used as the catalyst here; however, it reacts faster, which sometimes leads to undesired byproduct formation.

Quinoline as a Solvent.

When quinoline is used as a solvent for the reaction of Phenylcopper with iodoarenes, metal-halogen exchange and unsymmetrical coupling reactions occur as shown in eq 10.16 The products suggest that basic solvents such as quinoline solvate the phenylcopper, leading to a complex mixture of products. Similar activity is observed in pyridine solvent.

Acylation Reactions.

Many basic catalysts have been used to carry out acylation reactions. The stereoselectivity of the reaction of diacetoxy or dibenzoyloxysuccinic anhydrides with racemic alcohols is affected by the choice of base catalyst. Quinoline is one of the most effective base catalysts for enhancing the stereoselectivity of the reaction of (2R,3R)-2,3-diacetoxysuccinic anhydride with 1-phenylethanol in comparison with catalysts such as pyridine, 3- and 4-methylpyridines, and isoquinoline. Other effective basic catalysts are pyridine derivatives substituted in the 2-position of the ring such as 2-methylpyridine and 2,6-dimethylpyridine.17

Formation of Allenes.

Quinoline can be used as an acid scrubber in the preparation of allenes via vinyl triflate intermediates. The elimination of Trifluoromethanesulfonic Acid in quinoline proceeds in good yield (eqs 11 and 12).18

Rosenmund Reaction.

A catalyst poison prepared from quinoline and Sulfur is useful for controlling the reaction of b-naphthoyl chloride (19) with hydrogen gas and Palladium on Barium Sulfate catalyst.2 If control of the reaction is not maintained by catalyst poisoning to reduce activity, further reduction beyond the desired b-naphthaldehyde product (20) is often observed (eq 13).3

Elimination Reactions.

Quinoline in DMSO facilitates the elimination of dimethyl sulfide from sulfonium salt (21), affording the very reactive cyclobutenone derivative (22) (eq 14).19

Related Reagents.

Chromium(VI) Oxide-Quinoline; Copper Chromite-Quinoline.

1. Wiley, R. H.; Smith, N. R. OSC 1963, 4, 731.
2. Rosenmund, K. W.; Zetzsche, F. CB 1921, 54, 425.
3. Hershberg, E. B.; Cason, J. OSC 1955, 3, 627.
4. Holter, S. N. In Kirk-Othmer Encyclopedia of Chemical Technology; Wiley: New York, 1982; Vol. 19, p 532.
5. The Merck Index, 11th edn.; Budavari, S., Ed.; Merck: Rahway, NJ, 1989; p 1285.
6. The Sigma-Aldrich Library of Regulatory & Safety Data; Sigma-Aldrich: Milwaukee, WI, 1993; Vol. 2, p 2611.
7. Griesbaum, K.; Kibar, R. CB 1973, 106, 1041.
8. Odom, H. C.; Pinder, A. R. OSC 1988, 6, 883.
9. Schweizer, E. E.; Parham, W. E. JACS 1960, 82, 4085.
10. Lindsay, D. G.; Reese, C. B. T 1965, 21, 1673.
11. Matsumoto, H.; Kato, T.; Matsubara, I.; Hoshino, Y.; Nagai, Y. CL 1979, 1287.
12. Burness, D. M. OSC 1963, 4, 628.
13. Buckles, R. E.; Wheeler, N. G. OSC 1963, 4, 857.
14. George, B.; Papadopoulos, E. P. JHC 1983, 20, 1127.
15. Lewellyn, M. E.; Wang, S. S.; Strydom, P. J. JOC 1990, 55, 5230.
16. Nilsson, M.; Wennerstrom, O. TL 1968, 3307.
17. Bell, K. H. AJC 1981, 34, 671.
18. Stang, P. J.; Hargrove, R. J. JOC 1975, 40, 657.
19. Kelly, T. R.; McNutt, R. W. TL 1975, 285.

Angela R. Sherman

Reilly Industries, Indianapolis, IN, USA

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