Aldehydes heterocyclic

Imidazolines and isoxazolines. 1.3-Di and amides with N-tosylimines and aldehyde heterocycles. Interestingly, di-imidazolin m (runs-imidazolines are obtained on base[Pg.180]

Coldham, A. J. M. Burrell, L. Watson, N. Oram, N. G. Martin, Synthesis of fused tricyclic heterocycles by condensation, cyclization, dipolar cycloaddition cascade of a-benzenesulfonyl and a-phenylthio substituted aldehydes. Heterocycles 84 (2012) 597-613. 

Amidation. A number of other various amidation reactions have been conducted using BOP. Such preparations include A) O-dimethyl hydroxamates of amino acids and peptides (precursors of chiral peptidyl aldehydes), heterocyclic amide fragments in the synthesis of macrolide and porphyrin models, dan-sylglycine anhydride as a mixed sulfonic-carboxylic imide by dehydration-cyclization of dansylglycine, and selective monoacylation of heterocyclic diamine in carbohydrate series (eq 9). ... 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

Mills and Smith (504) were the first, in 1922, to develop a systematic study of the reactivity of methyl groups fixed on nitrogen-containing heterocycles. While in alkylpyridines the 2- (or 6) and 4-positions are activated, only the 2-position in thiazole corresponds to an enhanced reactivity of the methyl groups in condensation with aldehydes 4- and 5-methylthiazoles bear inert methyl groups. Quatemization of the thiazole nitrogen enhances still further the reactivity of the methyl in the 2-position (cf. Chapter IX), but it does not increase the reactivity of a methyl group in the 4-position (504). The authors invoke the possibility for 2- (and 6) methylpyridine and 2-methylthiazole to pass, to some extent, into the reactive enamine form (245), while 4-methylthiazole could adopt such a structure only with the participation of an unusual formula such as 247 (Scheme 112). 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

In most cases the frequencies of substituent groups attached to these heterocycles differ little from those observed for their benzenoid counterparts. The only notable exception is the spectral behaviour of carbonyl groups attached to position 2. These have attracted much attention as they frequently give rise to doublets, and occasionally multiplets. In the case of (34), (35) (76JCS(P2)l) and (36) (76JCS(P2)597) the doublets arise from the presence of two conformers (cf. Section 3.01.5.2), whereas for the aldehydes (37) the doublets are... 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

Aldehydes, ketones and cumulated double bonds react with oxiranes to form five-membered heterocycles (e.g. Schemes 31 and 32) (64HC(19-1)453). 

Michael addition of aromatic or heterocyclic aldehydes (via cyanohydrins) to o. unsaturated systems. Also addilion of aliphatic aldehydes catalyzed by thiazoFium yKds... 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

The study of structure and reactivity of tertiary heterocyclic enamines is associated with the problem of equilibrium of the cyclic enamine form (70) and the tautomeric hydration products 173,174) quaternary hydroxide (71), pseudo base (so-called carbinolamine) (72) and an opened form of amino aldehyde or amino ketone (73). 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

From the addition reaetions of acrolein- to aldehyde-derived enamines, aminotetrahydropyrans have been obtained. On heating, these products rearranged to enaminoaldehydes in examples where the initial enamine was disubstituted (320,321). The addition of acrolein to ketone derived enamines has been applied to syntheses of heterocyclic and bridged bieyclic compounds (301,321-323). 

Hydrazine and its derivatives find considerable use in the synthesis of biologically active materials, dyestuff intermediates and other organic derivatives. Reactions of aldehydes to form hydrazides (RCH=NNH2) and azines (RCH=NN=CHR) are well known in organic chemistry, as is the use of hydrazine and its derivatives in the synthesis of heterocyclic compounds. 

While mechanistically this reaction is related to the Robinson-Schopf reaction for the generation of the tropinone skeleton, it also has similarities to the Hantzsch reaction. Here the heterocyclic ring 75 is assembled by the condensation of an equivalent of acetonedicarboxylic ester 72 with 2 equivalents of aldehyde 73 in the presence of ammonia or primary amine 74. 

The Pictet-Spengler reaction is one of the key methods for construction of the isoquinoline skeleton, an important heterocyclic motif found in numerous bioactive natural products. This reaction involves the condensation of a P-arylethyl amine 1 with an aldehyde, ketone, or 1,2-dicarbonyl compound 2 to give the corresponding tetrahydroisoquinoline 3. These reactions are generally catalyzed by protic or Lewis acids, although numerous thermally-mediated examples are found in the literature. Aromatic compounds containing electron-donating substituents are the most reactive substrates for this reaction. 

Thiophenealdehydes have been condensed with aliphatic aldehydes, methyl ketones,cyclic ketones, " benzyl cyanides,and aliphatic nitro compounds to the corresponding vinylthiophenes. By the use of potassium methylate, 2-thiophenealdehyde has been condensed with the reactive methyl groups of iV-heterocyclic compounds. Thiophenealdehydes have... 

In the case of the bases derived from quaternary heterocyclic ammonium salts, the carbinolamines (5) can react as cyclic aldehyde-ammonias with many reagents with which the amino-aldehyde (7) could react. However, reactions of the carbinolamines which are not characteristic of amino-aldehydes are also known. Carbinolamines can easily be reconverted into the quaternary salts by the action of dilute acids, and they form alkyl ethers very easily with alcohols. If these last reactions do not occur, then this is convincing evidence for the base possessing the amino-aldehyde structure. However, if these reactions do occur this does not provide unambiguous confirmation of the carbinolamine structure. They are also given by the bi-molecular ethers (8), and, in the case of a tautomeric equilibrium... 

Recently, a one-pot method for preparation of 2-aryl-1,5-benzotelluroazepines 60 has been developed based on the reaction of sodium 2-aminophenyltellurolate [from di(o-aminophenyl) ditelluride) with arylpropargyl aldehydes (99MI1). Considering the high affinity of supemucleophilic aryltellurolate anions to a triple bond, one may assume that at the first stage of this reaction arylvinyl tellurides 61 are formed. Cyclization of 61 spontaneously or on silica gel in a chromatographic column forms the heterocycles 60. 

Synthesis of heterocyclic amines by hydrogenative amination of aldehydes and ketones 99MI29. 

Synthesis of 2-R-substituted thiazoles and transformation of a thiazole heterocycle into aldehyde group by successive N-methylation, reduction, and subsequent hydrolysis 98S1681. 

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