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Encyclopedia of Reagents for Organic Synthesis || Quinoline
2
QUINOLINE 1 Quinoline N [91-22-5] C 8 H 7 N (MW 129.16) InChI = 1/C9H7N/c1-2-6-9-8(4-1)5-3-7-10-9/h1-7H InChIKey = SMWDFEZZVXVKRB-UHFFFAOYAU (useful as a base, solvent and/or catalyst, especially for decar- boxylation reactions 1 and the Rosenmund reaction 2,3 ) Physical Data: mp −15 ◦ C; bp 237.6 ◦ C; 4 steam volatile; d 1.0858 g cm −3 at 30 ◦ C; pK a 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 mois- ture; LD 50 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 be- cause of its basic properties. A wide variety of substrates, rang- ing 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 quino- line to give a mixture of products, 3-methyl-2-butanone (2) and 2-methyl-1-buten-3-one (3) (eq 1). 7 O Br O O quinoline + (1) (1) (2) 11% (3) 43% 210 °C Trans-3-penten-2-one (5) has been prepared from 4-chloropen- tan-2-one (4) using quinoline as the acid scavenger (eq 2). 8 (4) (5) 25–37% overall from propylene and acetyl chloride quinoline (2) O Cl O H H ∆ Dehydrochlorination of 2-oxa-7,7-dichloronorcarane (6) in quinoline gives an 83% yield of 2,3-dihydro-6-chlorooxepine (7) (eq 3). 9 (3) quinoline O Cl Cl O Cl (6) (7) 140–150 °C 83% 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 (4) quinoline Br Br (8) (9) 200 °C 66% Selective dehydrobromination of (α-bromovinyl)chlorosilanes can be carried out in quinoline, affording fair to good yields of the corresponding ethynylchlorosilanes (eq 5). 11 quinoline (5) Si Cl Si Cl Me Br Me Me Me 180–200 °C 77% Decarboxylation Reactions. Taking advantage of its basic properties, quinoline is generally useful as a solvent for decar- boxylation reactions. It is especially suitable because its rela- tively high boiling point facilitates the decarboxylation. Exam- ples 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 α-phenylcinnamic acid (14) to cis-stilbene (15) (eq 8). 13 Copper catalysts such as (Copper or Copper Chromite are used to effect the decarboxylations. (6) Cu 0 , quinoline (11) CO 2 H O O (10) 250 °C 83–89% Cu 0 , quinoline (12) (13) (7) CO 2 H NO 2 NO 2 185–195 °C 56–60% (15) CO 2 H (14) Cu chromite quinoline (8) 210–220 °C 62–65% Preparation of Isothiocyanates. Ethoxycarbonyl Isothio- cyanate (18), useful as a synthetic reagent for heterocyclic syn- theses, 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 prod- uct 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. Avoid Skin Contact with All Reagents
Transcript of Encyclopedia of Reagents for Organic Synthesis || Quinoline
QUINOLINE 1
Quinoline
N
[91-22-5] C8H7N (MW 129.16)InChI = 1/C9H7N/c1-2-6-9-8(4-1)5-3-7-10-9/h1-7HInChIKey = SMWDFEZZVXVKRB-UHFFFAOYAU
(useful as a base, solvent and/or catalyst, especially for decar-boxylation 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 dissolvessulfur, 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 mois-ture; LD50 rat (oral) 460 mg kg−1; incompatible with strongoxidizing agents and strong acids.5,6
Dehydrohalogenation Reactions. Quinoline is sometimesused as a base or solvent for dehydrohalogenation reactions be-cause of its basic properties. A wide variety of substrates, rang-ing from very simple to quite complex compounds, have beeneffectively dehydrohalogenated with quinoline. For example, 3-bromo-3-methyl-2-butanone (1) underwent reaction with quino-line to give a mixture of products, 3-methyl-2-butanone (2) and2-methyl-1-buten-3-one (3) (eq 1).7
O
Br
O Oquinoline
+ (1)
(1) (2) 11% (3) 43%
210 °C
Trans-3-penten-2-one (5) has been prepared from 4-chloropen-tan-2-one (4) using quinoline as the acid scavenger (eq 2).8
(4) (5) 25–37% overall frompropylene and acetyl chloride
quinoline(2)
O ClO
H
H∆
Dehydrochlorination of 2-oxa-7,7-dichloronorcarane (6) inquinoline gives an 83% yield of 2,3-dihydro-6-chlorooxepine (7)(eq 3).9
(3)quinoline
O Cl
Cl
O
Cl
(6) (7)
140–150 °C83%
Similarly, when 7,7-dibromonorcarane (8) is treated withquinoline, by manipulation of reaction conditions thebromocyclohepta-1,3-diene derivatives can be isolated ortotal dehydrobromination to 1,3,5-Cycloheptatriene (9) can beeffected (eq 4).10
(4)quinoline
Br
Br
(8) (9)
200 °C66%
Selective dehydrobromination of (α-bromovinyl)chlorosilanescan be carried out in quinoline, affording fair to good yields of thecorresponding ethynylchlorosilanes (eq 5).11
quinoline(5)Si
Cl
Si
ClMe
BrMe
Me
Me180–200 °C
77%
Decarboxylation Reactions. Taking advantage of its basicproperties, quinoline is generally useful as a solvent for decar-boxylation reactions. It is especially suitable because its rela-tively high boiling point facilitates the decarboxylation. Exam-ples include the decarboxylation of 3-methyl-2-furoic acid (10)to 3-methylfuran (11) (eq 6),12 m-nitrocinnamic acid (12) tom-nitrostyrene (13) (eq 7),1 and α-phenylcinnamic acid (14) tocis-stilbene (15) (eq 8).13 Copper catalysts such as (Copper orCopper Chromite are used to effect the decarboxylations.
(6)Cu0, quinoline
(11)
CO2H OO(10)
250 °C83–89%
Cu0, quinoline
(12) (13)
(7)
CO2H
NO2 NO2
185–195 °C56–60%
(15)
CO2H
(14)
Cu chromitequinoline
(8)210–220 °C
62–65%
Preparation of Isothiocyanates. Ethoxycarbonyl Isothio-cyanate (18), useful as a synthetic reagent for heterocyclic syn-theses,14 can be prepared in excellent yield from the reaction ofEthyl Chloroformate (16) with Sodium Thiocyanate (17) usingquinoline as a base catalyst (eq 9).15 Only trace amounts of theisomeric thiocyanates are formed in the reaction. In the absence ofthe base catalyst, only a moderate (65%) yield of the desired prod-uct is obtained, along with significant (10%) contamination by theisomeric ethoxycarbonyl thiocyanate. Pyridine can also be usedas the catalyst here; however, it reacts faster, which sometimesleads to undesired byproduct formation.
Avoid Skin Contact with All Reagents
2 QUINOLINE
O
EtO Cl
O
EtO NCS+ NaSCN (9)
quinoline
(16) (17) (18)80%
Quinoline as a Solvent. When quinoline is used as a solventfor the reaction of Phenylcopper with iodoarenes, metal–halogenexchange and unsymmetrical coupling reactions occur as shown ineq 10.16 The products suggest that basic solvents such as quino-line solvate the phenylcopper, leading to a complex mixture ofproducts. Similar activity is observed in pyridine solvent.
Cu
OMe
I
OMeOMe OMe
(10)
+quinoline
+ +
4:3:1
50 °C, 25 h
Acylation Reactions. Many basic catalysts have been used tocarry out acylation reactions. The stereoselectivity of the reactionof diacetoxy or dibenzoyloxysuccinic anhydrides with racemicalcohols is affected by the choice of base catalyst. Quinoline isone of the most effective base catalysts for enhancing the stere-oselectivity of the reaction of (2R,3R)-2,3-diacetoxysuccinic an-hydride with 1-phenylethanol in comparison with catalysts suchas pyridine, 3- and 4-methylpyridines, and isoquinoline. Other ef-fective basic catalysts are pyridine derivatives substituted in the2-position of the ring such as 2-methylpyridine and 2,6-dimethyl-pyridine.17
Formation of Allenes. Quinoline can be used as an acid scrub-ber in the preparation of allenes via vinyl triflate intermediates.The elimination of Trifluoromethanesulfonic Acid in quinolineproceeds in good yield (eqs 11 and 12).18
OTf(11)
quinoline
100 °C79%
•
Et OTf Et(12)
quinoline
100 °C85%
•
Rosenmund Reaction. A catalyst poison prepared fromquinoline and Sulfur is useful for controlling the reaction of β-naphthoyl chloride (19) with hydrogen gas and Palladium on
Barium Sulfate catalyst.2 If control of the reaction is not main-tained by catalyst poisoning to reduce activity, further reduc-tion beyond the desired β-naphthaldehyde product (20) is oftenobserved (eq 13).3
(13)Pd, BaSO4, H2
O
HCl
O
(19) (20)
quinoline, S74–81%
Elimination Reactions. Quinoline in DMSO facilitates theelimination of dimethyl sulfide from sulfonium salt (21), affordingthe very reactive cyclobutenone derivative (22) (eq 14).19
O
Me2S
O
(14)
FSO3–
+
quinoline
(21) (22)
DMSO
Related Reagents. Chromium(VI) Oxide–Quinoline; CopperChromite–Quinoline.
1. Wiley, R. H.; Smith, N. R., Org. Synth., Coll. Vol. 1963, 4, 731.
2. Rosenmund, K. W.; Zetzsche, F., Chem. Ber. 1921, 54, 425.
3. Hershberg, E. B.; Cason, J., Org. Synth., Coll. Vol. 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., Chem. Ber. 1973, 106, 1041.
8. Odom, H. C.; Pinder, A. R., Org. Synth., Coll. Vol. 1988, 6, 883.
9. Schweizer, E. E.; Parham, W. E., J. Am. Chem. Soc. 1960, 82, 4085.
10. Lindsay, D. G.; Reese, C. B., Tetrahedron 1965, 21, 1673.
11. Matsumoto, H.; Kato, T.; Matsubara, I.; Hoshino, Y.; Nagai, Y., Chem.Lett. 1979, 1287.
12. Burness, D. M., Org. Synth., Coll. Vol. 1963, 4, 628.
13. Buckles, R. E.; Wheeler, N. G., Org. Synth., Coll. Vol. 1963, 4, 857.
14. George, B.; Papadopoulos, E. P., J. Heterocycl. Chem. 1983, 20, 1127.
15. Lewellyn, M. E.; Wang, S. S.; Strydom, P. J., J. Org. Chem. 1990, 55,5230.
16. Nilsson, M.; Wennerstrom, O., Tetrahedron Lett. 1968, 3307.
17. Bell, K. H., Aust. J. Chem. 1981, 34, 671.
18. Stang, P. J.; Hargrove, R. J., J. Org. Chem. 1975, 40, 657.
19. Kelly, T. R.; McNutt, R. W., Tetrahedron Lett. 1975, 285.
Angela R. ShermanReilly Industries, Indianapolis, IN, USA
A list of General Abbreviations appears on the front Endpapers
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