Substitution heterocycles

Recently the Bohlmann-Rahtz synthesis has received greater attention. Baldwin has employed this method for the construction of heterocyclic substituted a-amino acids. Exposure of alkynyl ketone 39 to 3-aminocrotoyl ester 40 resulted in the Michael product 41. Thermolysis then gave rise to the desired pyridyl-P-alanines 42. 

Novel heteroquaterphenoquinones were synthesized by a stepwise cross-coupling reaction or by a more convenient one-pot oxidative homocoupling reaction of the heterocycle-substituted phenols (Scheme 20, <96JOC4784 see also 95TL8055>). 

Phthalic anhydride condenses with the aniline derivative in the presence of zinc or aluminum chlorides to yield the intermediate benzoyl-benzoic acid, which subsequently reacts with l,3-bis-V,V-dimethylaniline in acetic anhydride to yield the phthalide. The above compound gives a violet-gray image when applied to a clay developer. Clearly this synthesis is also very flexible and variations in shades of color formers have been obtained by varying the aniline components and also by using phthalic anhydrides substituted, for example, by nitro groups or chlorine atoms. Such products have excellent properties as color formers and have been used commercially. Furthermore, this synthetic route is of great importance for the preparation of heterocyclic substituted phthalides, as will be seen later. 

Corrosion inhibition is primarily associated with acidizing. Buffered hydrofluoric acid compositions have been shown to be less corrosive (147). Corrosion inhibitors are designed to reduce the rate of reaction of fluid with metal surfaces, generally by forming films on the surfaces. Acetylenic alcohols and amines are frequently components of corrosion inhibitor blends. Other compounds that have been used include nitrogen heterocyclics, substituted thioureas, thiophenols, and alpha-aminoalkyl thioethers (148). 

Formation of this ring system was also reported in the reaction of a,/3-unsaturated ketones with substituted pyrrol-5-ones, giving the tricyclic products in 41—46% yield <2004PS(179)61>. 4-Thienyl and 4-furyl derivatives of a dihydropyrano[2,3- 5,6-c]dipyrazole were also obtained via the heterocycle-substituted acrylonitrile in 77% and 74% yield, respectively <2005RJ0742>. 

This approach involves intermolecular cyclization of two six-membered heterocycles substituted with appropriate functional groups. Synthesis of 83 by the reaction between 2-aminopyridines and 3-ethoxycarbonyM-pipcridonc hydrochloride 82 in polyphosphoric acid is provided as an example (Equation 5) <1996T7789>. 

Cyclocondensation processes of p-dicarbonyl derivatives or their analogues are still widely employed for the synthesis of new isoxazoles. Non-proteinogenic heterocyclic substituted ct-amino acids have been synthesised using the alkynyl ketone functionality as a versatile building block ynone 2, derived from protected L-aspartic acid 1, reacted with hydroxylamine hydrochloride affording the isoxazole 3 with enantiomeric purity greater than 98% ee <00 JCS(P 1 )2311 >. 

Among heterocyclic substituted 1-aminoanthraquinone derivatives, the 2 1 reaction product with 1-phenyl-2,4,6-triazine, also referred to as Pigment Yellow 147,60645, should be mentioned as an example [10]. It is a reddish yellow pigment with the chemical structure 87 ... 

E. E., Risen, L., Griffey, R. H. Design and synthesis of paromomycin-related heterocycle-substituted aminoglycoside mimetics based on a mass spectrometry RNA-binding assay. 

In summary, the sulfonylureas are new herbicides which exhibit activity at extremely low rates of application and show very low mammalian toxicity. Exceptionally high activity is shown by compounds containing a benzene ring substituted in the ortho position, an unsubstituted sulfonylurea bridge, and a pyrimidine or triazine heterocycle substituted with methyl or methoxy groups. 

Zhang W, Guo YP, Liu ZG, Jin XL, Yang L, Liu ZL (2005) Photochemically catalyzed Diels-Alder reaction of arylimines with N-vinylpyrrohdinone and N-vinylcarbazole by 2,4,6-triphenylpyrylium salt synthesis of 4-heterocycle-substituted tetrahydroquinoline derivatives. Tetrahedron 61 1325-1333... 

More complex examples exist where the 2-substituent on the furan is a polyhydroxyalkyl or glycosyl moiety <89CAR(l9l)209>. In these cases, the rearrangement products provide useful intermediates for the preparation of heterocycle-substituted sugar derivatives. Sometimes Baeyer-Vil-liger-type products are observed, such as 3-keto enoic esters instead of 3-keto enol esters <81TL1443>. 

For 64-70 reversible potentials RED 7SEM can be obtained at -55 °C only in DMF from which protic impurities have been removed One should keep in mind that here the levels RED (and SEM) exist as heterocyclic substituted cumulenes which may rapidly polymerize. 

The carbon dioxide/DBU procedure has been used synthetically for the synthesis of 5-heterocyclic substituted 2,4-quinazolinediones 820, although in this case it was necessary to operate at a much higher pressures than for the standard method <2006H(67)489>. 

Carreira and co-workers (138) successfully applied the Mg(II) ion-mediated nitrile oxide cycloaddition method to the total synthesis of epothilones A and B (Scheme 11.36). The key step in the synthesis was a hydroxyl-directed syn-selective nitrile oxide cycloaddition using a phosphorus-functionalized aliphatic nitrile oxide. This cycloaddition step served not only to introduce a heterocycle-substituted appendage into the skeleton of the epothilones, but also to assemble two... 

Functionalization of triazolopyridines was discussed in <1996CHEC-II(7)363> and it was concluded that there is no predominant factor which determines the site of N-functionalization. A recent example of this can be found in the report by Ding et al. of their synthesis of paromomycin-related heterocycle-substituted aminoglycoside mimics (Equation 1) <2003AGE3409>. 

Chlorinated Heterocyclics. Substitution in pyridine is more difficult than in benzene hut Cl will enter die ft position slowly. Chlorine will not add to furan to give stable addition products but substitution occurs to give 2-chloro- or 3-chlorofuran. 2.5-dichlorofuran. and 2.3.5-lriehlorofuran. 

The preparation of heterocyclic-substituted ethylene derivatives by direct condensation of aldehydes with activated methyl groups, as, for example, in the formation of 2-styrylbenzoxazole (1) has long been known.1 However, the analogous reaction of aldehydes with those... 

The previously available methods for the preparation of such compounds were somewhat limited in their application. First, the oxidative coupling of 2 molecules of a heterocyclic-substituted toluene derivative in lie presence of sulfur results in the formation of symmetrical stil-benes,4,5 as shown by the synthesis of 4,4 -bis(benzimidazol-2-yl)stilbene (2). The disadvantages of this method are the high reaction temperatures necessary and the difficulties often involved in product workup. 

The cycloaddition of diazomethane to SchifT bases from heterocyclic aldehydes and anilines provides a useful route to heterocyclic substituted triazolines. Unlike olefins bearing heterocyclic substituents, the heterocyclic imines can be obtained readily by reaction of the appropriate aldehyde and amine thus the diazomethane-imine addition has greater scope than the olefin-azide reaction. NMR spectroscopic studies of the orientation of addition are in accord with previously reported mechanistic considerations (see, e.g., Scheme 93).329 In addition to the influence of the N-aryl group, the electron-withdrawing power of the heterocyclic substituent on the Schiff-base carbon also has a substantial effect on imine reactivity, in the order 2-quinolyl 2-, 3-, or 4-pyridyl > phenyl > 2-thienyl as 2-furyl.329... 

Fluorinated triazolines (Scheme 29) are particularly stable and require high temperatures for thermolysis when aziridines are obtained.145 Thermolysis of aryl-substituted triazolines is not well investigated144,175 the l-p-nitrophenyl-5-phenyl compound yields exclusively aziridine, whereas the 1,4-isomer gives the imine as the major product.175 1-Heterocyclic-substituted 5-vinyltri-azolines (Scheme 31) give S-vinylaziridines, which undergo thermal isomerization to azepine derivatives (e.g., 89).183... 

Heterocyclic-substituted vinyl azides lead to pyrrole derivatives (Scheme 170).486... 

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