Pyridines from furans

Ammonium acetate Pyridine from furan ring 3-Hydroxy-2-aryipyridines... 

While the synthesis of benzofuran derivatives from suitable furan derivatives has been comparatively little investigated, the synthesis of fused two-ring and three-ring compounds containing a pyridine nucleus from furan derivatives has been more successful furo[3,2-c]pyridines (345),752>753 2,3-dihydrofuro[2,3-a ]quinolines (from 4,5-dihydro-3-furoic acid),754 acrophyllin (346), and 7-hydroxydictamnine (347) (from ethyl 2-ethoxy-4-oxo-4,5-dihydrofuran-3-carboxylate),755 are examples of compounds in this class which have been prepared. 

Synthetic approaches to furopyridines start either from pyridines or from furans. 

Several routes are available for the preparation of furo[3,2-c]pyridine itself starting both from furan (Scheme 12) (71BSF1727, 71JHC57, 74BSF515) and from pyridine derivatives (Scheme 13) (71CR(C)(272)2197, 72BSF1442). The latter synthesis gives (8) in an overall yield of 12%. 

Oxazole, imidazole, and thiazole can be formally derived from furan, pyrrole, and thiophene respectively by replacement of a CH group by a nitrogen atom at the 3 position. The presence of this pyridine-like nitrogen deactivates the 1,3-azoles towards electrophilic attack and increases their susceptibility towards nucleophilic attack (see later). These 1,3-azoles can be viewed as hybrids between furan, pyrrole, or thiophene, and pyridine. 

Nevertheless, this collection of heterocycles does share certain characteristics. The trend we have seen of decreasing tendency towards electrophilic substitution on going from furan, pyrrole, and thiophene to the azoles is continued into these series. The presence of additional pyridine-like nitrogen atoms renders these systems particularly electron-deficient, and electrophilic substitution is of little importance. 

Finally, the formation of derivatives of pyridine from 5-hydroxymethylfurfural and related compounds on treatment with ammonia 0 may be considered in this section on the furan ring. 5-Hydroxymethyl-furfural itself gives 2-hydroxymethyl-5-hydroxypyridine (XLIV) with ammonia, which is presumably formed by opening of the ring in the intermediate aldehyde-ammonia compound followed by closure to give the 6-membered ring. 

It is, in a sense, impossible to summarize this section. The entire chapter is really a summary of a vast field of chemical endeavor. Compounds having a range of sizes from about nine atoms to five or six times that number have been prepared. Almost every permutation of O, S, and N has been incorporated in simple macrocycles and these heteroatoms have also been included as part(s) of small-ring heterocycles such as pyridine, thiophene, furan, etc. This chapter attempts to present a broad, if superficial, view of the possibilities and the precedents. An attempt has been made to indicate something about cation binding since this has been the driving force for much of the development in this area. 

The paper is divided into six parts, an abstract, and an appendix with mathematical details. Part 1 gives an introduction and outline of the problem, which shows that the physicist Erich Huckel had a pronounced knowledge about the chemical and physical properties of aromatic compounds. The chemical knowledge was certainly aquired from discussions with his brother Walter Huckel, who was a chemistry professor and textbook author [14]. Huckel discusses benzene, pyridine, pyrrol, furan, thiophene, isomeric forms of dihydrobenzene and chinone, cyclobutadiene, cyclooc-tatetraene, and cyclopentadiene. He points out that there is no satisfactory explanation for the observation why cyclobutadiene does not (at that time) exist, and why benzene and cyclooctatetraene are stable but chemically very different in their reactivity. Huckel emphasizes that the number 6 appears to play a particular role for aromatic compounds, which had been pointed out for the first time by Bamberger in 1890 [15]. 

Hantzsch s first important research was the synthesis of pyridine from acetoacetic ester and aldehyde ammonia, a general method of synthesis of pyridine derivatives. Coumarone, discovered by Fittig and Ebert (see p. 768), was (with some derivatives) synthesised by Hantzsch, who called it the fur-furane of the naphthalene series . He synthesised thiazole, and benzene, pyridine, and thiophen derivatives from derivatives of pentamethylene, and pyrrole, investigated tetrazoles, and perthiocyanic acid C2N2S3H2 (discovered by Wohler), giving it a cyclic structure." ... 

Analogous complexes with chloro and fluoro substituents on the aromatic group have been prepared 623-628." A methylplatinum complex with the CNN ligand formed from furan carboxyaldehyde has been prepared 629, while the imine of 3-pyridine carboxyaldehyde coordinates as an iV,A -bidentate chelate and does not undergo cyclometallation 630. ... 

It is well known that 2,6-diheteroaryl-containing pyridines display important biological properties such as antitumor and cyclin-dependent kinase inhibitory activities. Also, the introduction of ferf-butyl group into some heterocycles can greatly enhance their biological activity. Recently, Vang et al. [99] described a facile ultrasound-assisted synthesis of new 2,6-bis(5-fcrf-butyl-benzo[fc]furan-2-ylcarbonyl)pyridines from 2,6-bis(bromoacetyl)pyridine with f-butyl-substituted salicylaldehydes in acetonitrile in the presence of nontoxic and inexpensive catalyst as PEG-400. The new heterocyclic compounds were synthesized in short reaction times under mild reaction conditions with satisfactory yields. 

Chemical vapor deposition (CVD) of some organic compounds was examined to control the porosity and surface function of active carbon fiber (ACF). In this system, the deposition takes place only on the pore wall of the ACF, when the precursor organic compound and deposition temperature around 700 C were selected carefully. The surface of the ACF was modified by carbon derived from heterocyclic compounds (pyridine, pyrrole, furan and thiophene) through CVD. The moderately activated ACF modified by pyridine, pyrrole and thiophene showed molecular sieving activity, that modified by furan did not. Only fiiran was decomposed at this temperature. Thermal stability is a key factor to get molecular sieving performance after CVD. Pyridine produced amorphous carbon within the pore, which appears to maintain the pyridine ring structure, creates basic sites over the surface of the ACF. Thus catalytic oxidation of SOx over ACF of high surface area was accelerated. 

Pyridine pyrrole and thiophene like benzene are present m coal tar Furan is pre pared from a substance called furfural obtained from corncobs... 

Heterocychc compounds range from those, such as furan which is readily halogenated and tends to give polyhalogenated products, to pyridine which forms a complex with aluminum chloride that can only be brominated to 50% reaction (23). 

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