Preparation of quinolines from α-methylene-ketones

Gagan, J. M. F.; Lloyd, Douglas

doi:10.1039/j39700002488

Cited by 15 publications

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“…Several attempts to oxidize 1 directly to 12 were unsuccessful. One product isolated from these attempts was 3-methylpicolinic acid (13), also a possible metabolite of 1 resulting from /3-oxidation of preliminarily formed 12. 13 was more conveniently synthesized by oxidizing 2,3dimethylpyridine (14) with selenium dioxide, according to the method of Jerchel, Bauer, and Hippchen. 11 An alternative, successful route to 12, as well as to other interesting structures (15)(16)(17), is shown in Scheme I.…”

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confidence: 99%

Synthesis and hypoglycemic activity of pyridylalcohols

Blank¹,

DiTullio²,

Krog³

et al. 1979

J. Med. Chem.

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The potent hypoglycemic activity of 3-(3-methyl-2-pyridyl)propan-1-ol (1) prompted us to synthesize and study related structures. Some of the variables studied were the position of the methyl and alcohol side chains, the distance between the heterocyclic ring and the hydroxyl group, the effect of additional nuclear substitution, and the effects of branching and substitution on the alcohol side chain. The compounds were tested in 48-h fasted rats, usually at a dose of 150 mg/kg po. 1, the corresponding propionic acid 12, the acetate and methyl ether of 1 (22 and 23), and the 5-methyl analogue of 1 (29) were of comparable hypoglycemic potency. However, these compounds all caused a concomitant elevation of hepatic triglycerides and/or death in the test animals when observations were continued for 4--24 h.

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confidence: 99%

Synthesis and hypoglycemic activity of pyridylalcohols

Blank¹,

DiTullio²,

Krog³

et al. 1979

J. Med. Chem.

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“…Thus, 2,3-disubstituted quinolines have been obtained, when N-aryl-vinamidinium chlorides were heated in refluxing glacial acetic acid or alcohols with similar boiling points. [23] 2,4-Bis(dimethylamino)quinolines resulted from 1,3-dichloro-N,N,N',N'-tetramethyl-vinamidinium salts and aniline in the presence of triethylamine. [24] Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

A Convenient Synthesis of 4‐CF₃‐Quinolines from 1‐Trifluoromethyl‐prop‐2‐yne 1‐Iminium Salts and Arylamines

et al. 2021

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A convenient synthesis of 4-trifluoromethyl-quinolines from 1trifluoromethyl-prop-2-yne 1-iminium triflates and anilines in a one-pot two-step Michael addition/intramolecular cyclization sequence is reported. With ring-substituted anilines, a wide range of 4-CF 3 -quinolines bearing additional substituents and functional groups in the C-2, C-6, and C-8 positions were prepared, mostly in high yields. Even a 4-CF 3 -5-Me-quinoline could be obtained. From mono-Boc protected 1,4-and 1,3-phenylenediamine, 2-aryl-substituted 6-amino-4-CF 3 -quinoline and 7-amino-4-CF 3 -quinoline, respectively, were prepared. 4-CF 3 -benzo[h]quinolines were obtained from the mentioned acetylenic iminium salts and 1-naphthylamine. With N-monosubstituted aromatic amines such as N-methylaniline and 1,2,3,4-tetrahydroquinoline, N-substituted 4-CF 3 -quinolinium salts and pyrrolo[1,2-a:3,4-c']diquinoline derivatives bearing two CF 3 substituents could be prepared.

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“…9 Vinamidinium salts have also been used to synthesize quinolines via a modified Friedländer synthesis. 10 The preparation of more highly substituted quinolines from a-methylene ketones via a "vinamidinium" type mechanism 11 has also been reported.…”

Section: Methodsmentioning

confidence: 99%

An Efficient Synthesis of Substituted Quinolines

Tom¹,

Ruel²

2001

Synthesis

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The addition of substituted anilines to "vinamidinium" bis-tetrafluoroborate salt 1 [2-dimethylaminomethylene-1,3-bis(dimethylimmonio)propane bis-tetrafluoroborate], followed by cyclization of the resulting imino-eneamine salt and hydrolysis of the masked aldehydes 2, provide the corresponding 3-formyl quinolines 3. While the condensation of both 1 and its analogous bisperchlorate salt and amidines are known to provide pyrimidines, we believe this is the first example of a quinoline annulation sequence with "vinamidinium" bis-tetrafluoroborate salt 1 and anilines.The preparation of quinolines has been known since the late 1800s. The Friedländer quinoline synthesis 1 can be defined as a condensation followed by cyclodehydration of a substituted o-amino aromatic aldehyde or ketone with another carbonyl compound containing a reactive a-methylene group (Scheme 1). Although it does not require catalysis, the Friedländer synthesis can be acid-or basecatalyzed. The Pfitzinger reaction 2 (Scheme 2) and the Niemantowski reaction 3 (Scheme 3) are considered extensions of the Friedländer synthesis differing only in the starting materials. Some of the restrictions of these three methods involve the substitution pattern on the available starting materials and thus, limits the functional groups on the product quinoline, and high temperatures in some cases. Scheme 1 Scheme 2 Scheme 3The Combes 4 (Scheme 4), Skraup 5 (Scheme 5), and Doebner-Miller 6 (Scheme 6) quinoline syntheses were also reported in the late 1800s. The Combes method involves heating an aniline with acetylacetone. The Skraup and Doebner-Miller syntheses are very similar. The former involves heating an aniline with acrolein, generated in situ from glycerol and a strong acid, and the latter method is based on generating a substituted acrolein intermediate. Both reactions also require an oxidant. Although subsequent work on these methods has extended the scope of these reactions, the substitution patterns that can be obtained on the product quinolines is still limited. Other major limitations are the high temperatures (>250 °C) and highly acidic conditions that are required. Scheme 4Scheme 5 Scheme 6There has been a report of "vinamidinium" mono-perchlorate salts 7 and a report of a synthetic equivalent of "vinamidinium" type salts 8 undergoing condensation and intramolecular cyclization with anilines to provide 3-substituted quinolines. The substitution has been limited to X NH 2 O R O R 1 R 2 N R 2 R R 1 X + X NH 2 O CO 2 H O R R 1 N R 1 CO 2 H R X + X NH 2 O OH O R R 1 N R 1 OH R X + X NH 2 O Me N Me Me X O M e + X NH 2 N X CHO + X NH 2 N X R R R 1 R 2 O R 2 R 1 + Downloaded by: Collections and Technical Services Department. Copyrighted material.

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Preparation of quinolines from α-methylene-ketones

Cited by 15 publications

References 0 publications

Synthesis and hypoglycemic activity of pyridylalcohols

Synthesis and hypoglycemic activity of pyridylalcohols

A Convenient Synthesis of 4‐CF₃‐Quinolines from 1‐Trifluoromethyl‐prop‐2‐yne 1‐Iminium Salts and Arylamines

An Efficient Synthesis of Substituted Quinolines

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Preparation of quinolines from α-methylene-ketones

Cited by 15 publications

References 0 publications

Synthesis and hypoglycemic activity of pyridylalcohols

Synthesis and hypoglycemic activity of pyridylalcohols

A Convenient Synthesis of 4‐CF3‐Quinolines from 1‐Trifluoromethyl‐prop‐2‐yne 1‐Iminium Salts and Arylamines

An Efficient Synthesis of Substituted Quinolines

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A Convenient Synthesis of 4‐CF₃‐Quinolines from 1‐Trifluoromethyl‐prop‐2‐yne 1‐Iminium Salts and Arylamines