H. C. Van Der Plas

Novel ring transformations of pyrazines by intramolecular Diels-Alder reactions.

Abstract Pyrazines carrying the ω-alkyne side-chain -XCH2CH2C≡CH, (X = 0,N,S,SO,SO2, C(CN)2) undergo on heating an intramolecular Diels-Alder reaction. Pyrazines with the electron donating atom (0,N or S) in the side-chain afford [c]-fused pyridines as main products, whereas (3-buty-nylsulfinyl)pyrazine and (3-butynylsulfonyl)pyrazine are exclusively converted into [b]-fused pyridines. A [b]-fused pyridine is also the major product in the reaction of 2,5-bis(1,1-dicyano-4-pentynyl)pyrazine.

Ring-transformations of pyrimidines by intramolecular Diels-Alder reactions. Synthesis of annelated pyridines.

Abstract Pyrimidines carrying an ω-alkyne side-chain -XCH 2 CH 2 CCH (X=O,N,S,SO,SO 2 ) at the 2 or 5 position undergo intramolecular inverse electron demand Diels-Alder reactions across the C-2 and C-5 positions; elimination of hydrogen (or alkyl) cyanide from the intermediate adducts leads to condensed pyridines. The influence of the hetero atom (X) in the dienophilic side-chain and that of substituents in the pyrimidine ring on the reactivity is discussed.

Inverse electron demand Diels-Alder reactions of 5-nitropyrimidine with enamines: synthesis of 3-nitropyridine derivatives

Abstract The reaction of cyclic and non-cyclic enamines with 5-nitropyrimidine has been studied. Many enamines react in an inverse electron-demand Diels-Alder reaction, leading to the formation of 3-nitropyridines. N,S-ketene acetals were also found to react with 5-nitropyrimidine. The mechanism of the reaction will be discussed.

Intramolecular Diels-Alder reactions of pyrimidines: Synthesis of tricyclic annelated pyridines.

Abstract 2-(2-Trimethylsilylethynylphenyl-X)-pyrimidines (2, X= O, S, NAc, CH2, CO) easily undergo intramolecular Diels-Alder reaction with inverse electron demand, to give tricyclic annelated pyridines in excellent yields. The synthesis of 2 and the cycloaddition reaction to give the tricyclic annelated pyridines is described.

Reactions of Azines with Bifunctional Nucleophiles: Cyclizations and Ring Transformations

Publisher Summary Reactions of azines with bifunctional nucleophiles can give rise to several cycloadducts, the structure depending on the nature of reagents, the structure of the azine substrate, and the reaction conditions. Three types of cycloadducts are proposed to be formed in reactions of azines with such 1,3-N,C-dinucleophiles as acetamidines and acetimino esters. Ortho-cyclization products can usually be isolated, while meta- and para-bridged cycloadducts are unstable and are often transformed into other heterocyclic systems. Their presence as intermediates can, however, often is rationalized by spectroscopic methods or 15 N-labeling studies. Many of the reactions discussed provide a very convenient synthetic route to a great variety of azine derivatives. It seems to be a very interesting and promising area of heterocyclic chemistry and there is no doubt that further investigations into this field also allow new syntheses of useful compounds to be developed.

Reactivity of Naphthyridines toward Nitrogen Nucleophiles

Publisher Summary This chapter summarizes the reactions that naphthyridines can undergo with KNH 2 /NH 3 . Naphthyridines are heterocyclic systems consisting of two fused aromatic rings, each one containing one nitrogen atom. The addition occurring between naphthyridines or substituted naphthyridines and azanucleophiles occurs by covalent amination of the parent naphthyridines and substituted naphthyridines. The chapter focusses on nucleophilic substitutions using nitrogen nucleophiles such as amide ions and liquid ammonia. Ring transformations that the naphthyridines can undergo are also discussed. The complex behavior of the naphthyridines toward the reagent (ipso, tele, and cine substitutions, as well as ring transformations) is also provided in a tabular form.

Behavior of monocyclic 1,2,4-triazines in reactions with C-, N-, O-, and S-nucleophiles

Publisher Summary Among the six-membered nitrogen-containing heterocycles the 1,2,4-triazines have attracted the attention of chemists for a long time. This is due to the fact that many 1,2,4-triazine derivatives are biologically active and are used in medicine and agriculture. Moreover, 1,2,4-triazines are of chemical interest. They proved to be very susceptible to attack by all kinds of nucleophiles, leading to the addition, and subsequently either substitution or cyclization, and ring transformation. This continuing and lively interest in this area of heterocyclic chemistry has produced a great number of publications and patent applications. This chapter concentrates on the behavior of monocyclic 1,2,4-triazines in reactions with C-, N-, 0-, and S-nucleophiles, because the important features of general character established for simple 1,2,4-triazines can evidently be applied to other derivatives including condensed 1,2,4-triazines.

Intramolecular Diels-Alder reactions of 2-(alkynyl)pyrimidines and 2-(alkynyl)pyridines.

Abstract Pyrimidines 3, 7 and 13 carrying an ω-alkynyl side-chain -CR2(CH2)nCH2CCH (R = H, CN; n = 1, 2) at the 2-position undergo intramolecular inverse electron demand Diels-Alder reactions across the C-2 and C-5 positions. Loss of hydrogen cyanide, caused by a retro-Diels-Alder reaction, from the intermediate cycloadducts leads to annelated pyridines 5, 9 and 15, respectively. Similarly, from the nitropyridines 16 the 2,3-dihydronitro-1H-indenes 18 are obtained. The influence of electronic and steric effects on the rate of cycloaddition is discussed. Gem-disubstitution on the chain connecting the reaction centers leads to a considerable rate enhancement for compounds 3 vs 13. Compounds 7, having an extra methylene group in the tether between diene and dienophile, react much slower than compounds 3 due to decreased entropic assistance.

Reactivity of 3-alkynylthio-1-ethyl-1,2,4-triazinium salts in intramolecular Diels-Alder reactions

Abstract Quaternization of 3-(3-butynylthio) and 3-(4-pentynyltio) substituted 1,2,4-triazines with triethyloxonium tetrafluoroborate in CH2Cl2 at room temperature occurs exclusively at N-1 yielding 3-alkynylthio-1-ethyl-1,2,4-triazinium salts, as unequivocally shown by the 13C NMR and X-ray crystallographic data. 3-Alkynylthio-1-ethyl-5-phenyl-1,2,4-triazinium salts undergo the intramolecular Diels-Alder reaction into the corresponding thieno [2,3-b]- and thiopyrano [2,3-b]pyridines under considerably milder conditions than the corresponding neutral 1,2,4-triazines.

Intramolecular diels-alder reactions of pyrazines with alkynylphenyl moieties as side-chain dienophiles

Abstract Intramolecular Diels-Alder reactions of (2-alkynylphenyl-X)-pyrazines (X = O, NAc, S) under neutral and acidic conditions are described. The isomer distribution of the resulting tricyclic b - and c -annelated pyridines is discussed.