Aldehyde hydrazones

A series of interesting pyrazolo[3,4-(f pyrimidine derivatives was obtained by a thermal denitrocyclization reaction of hydrazones, e.g. 164 or 166, easily formed from the corresponding aldehyde or ketone hydrazones with halo-nitrouracil derivatives, e.g. 163 (71CC1442, 72CC298). Intermediates 164 or 166 can be isolated and their cyclization in suitable solvents (methanol, DMF, DMSO) provided high yields of the products. Aldehyde hydrazones yielded the corresponding l,7-dihydropyrazolo[3,4-J]pyrimidines, e.g. 165, whereas ketone hydrazones gave l,5-dihydropyrazolo[3,4-pyrimidine derivatives, e.g. spirocyclic compound 167 (Scheme 26). 

No corresponding reactions have been reported with ImCSIm. Attempts to extend the reaction to other aldehyde hydrazones (e.g., acetaldehyde-A /V-dimethylhydrazone) failed.[10]... 

This work demonstrates that functionalization of the internal cavities of various dendrimers can be done via a post modification of the skeleton. Various functional groups can be selectively introduced aminophosphite, aldehyde, hydrazone, dichlorophosphane sulfide. Therefore all the chemistry reported on the surface of dendrimers can be now envisaged to be done into the cavities and it is demonstrated for the first time that a macromolecular chemistry can be performed into the internal voids of a dendrimer. 

Oxidative processes (route B) represent another common route to triazolopyridines (compounds described in Schemes 54 and 55). These preparations all start from aldehyde hydrazones and use different oxidative reagents for the cyclization (Table 2). Generally, those conditions are milder than condensation methods. Moreover, the oxidizing reagents are compatible with other moieties, even the sugar-derived polyol 209. In the case of compound 208, the hydrazone (major diastereomer) was obtained by tautomerization of the corresponding enhydrazine, the... 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

In 1981 we published the first paper [22] on the synthesis of s-triazolo[4,3-a]pyridinium salts, 4, by the anodic oxidation of hydrazones 3 in the presence of pyridine (Scheme 5). In our working mechanistic scheme we proposed nitrilimine as the possible intermediate and pointed out that this reaction opens the door to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydrazones through 1,3-dipolar cycloaddition reactions of the nitrilimine involved. 

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

The radical cations (47) produced by T oxidation of aryl aldehyde hydrazones acted as 1,3-dipoles in reaction with nitriles to form, after a second T oxidation, 1,2,4-triazoles (Scheme 4) (85TL5655). 

H-NMR spectroscopic features of SAMP/RAMP-hydrazones include a singlet for the methoxy group at 3.2 3.3 ppm and, in the case of aldehyde hydrazones, a triplet for the imine hydrogen at 6.4 6.5 ppm. 

In addition to the results described, enantioselective access to 2-phosphino alcohols could be accomplished, too [71]. Starting from a borane-protected a-phosphino aldehyde hydrazone 91 as the key intermediate and available by two different approaches, the enantioselective synthesis of the desired 2-phosphino alcohols 93 could be accomplished. Thus, the electrophilic phosphinylation of aldehyde hydrazones 90 (via route I with the chlorodiphenylphosphine-borane adduct or via route II with chlorophosphines and subsequent phosphorus-boron bond formation) and the alkylation of phosphino acetaldehyde-SAMP hydrazones 92 (route III) was carried out (Scheme 1.1.26). 

The reaction of aldehyde hydrazones is more complex and requires further study [103]. It is usually carried out with a 90% solution of lead tetraacetate in acetic acid with sufficient additional solvent to bring about homogeneous reaction conditions initially. 

In the latest development of his elegant work with hydrazone derivatives, Andrew Myers of Harvard reports (J. Am. Chem. Soc. 2004,126, 5436) that Sc(OTf), catalyzes the addition of l,2-bis(r-butyldimethylsilyl)hydrazine, to aldehydes and ketones to form the t-butyldimethylsilylhydrazones. Addition of tBuOH/tBuOK in DMSO to the crude hydrazone effects low temperature Wolff-Kishner reduction. Alternatively, halogenation of ketone hydrazones can lead to vinyl halides such as 11, or the 1,1-dihalo derivatives, depending on conditions. Halogenation of aldehyde hydrazones provides the 1,1-dihalo derivatives such as 13. 

The butanals form the conventional aldehyde hydrazone, semicarbazone, and dimedone-type derivatives. In the absence of other aldehydes and ketones, /2-butyraldehyde can be determined by addition of sodium bisulfite and the excess bisulfite determined with iodine or thiosulfate (34). 

Polyaza rings suffer complete hydrolytic ring cleavage. Monocyclic 1,2,3-triazines are hydrolyzed by acid to yield 1,3-dicarbonyl compounds (Scheme 15). 1,2,3-Benzotriazines are easily converted into derivatives of 2-aminobenzaldehyde. 1,2,4,5-Tetrazines (180) are hydrolyzed with a base to give aldehyde hydrazones, RCH = NNHCOR. 

A variety of arylhydrazines have been reacted with isatins to give isatin-3-arylhydrazones (83).15,21,22,24,78,80,107,156,181,216,300-306 Similar reactions have also been carried out with isatins and alkylhydrazines,307 hydrazides,155 188,304 305,308-312 and hydrazine21,156,157,216,313-315 to give 84, 85, and 86, respectively. Aldehyde hydrazones also react with... 

Hydroxy-l-nitrohydrazones (809) react with primary amines and formaldehyde to give 2,3,4,5-tetrahydro-l,2,4-triazines (810) (64MI21901), and similar compounds (812) can be obtained from the reaction of aldehyde hydrazones (811) with primary amines and aldehydes (74KGS425, 75KGS1290, 74UKZ1220). 

Treatment of 3-phenyl-l,6-dihydro-l,2,4,5-tetrazin-6-one (94) with base led to the isolation of benzalazine (82) (69KGS566). Alkaline hydrolysis of hexahydro-1,2,4,5-tetrazines (74) gave an aldehyde hydrazone or an aldehyde and hydrazine as with the acidic hydrolysis <78HC(33)1075, p. 1213). 

Thermolysis of 3,6-diphenyl-l,4-di(phenylsulfonyl)-l,4-dihydro-l,2,4,5-tetrazine (127) in boiling toluene gives benzenesulfonic anhydride (128), phenyl benzenethiosulfonate (129), small amounts of diphenyl disulfide (130), 3,6-diphenyl-l,2,4,5-tetrazine (51) and a rearrangement product, 3,6-diphenyl-l,2-di(phenylsulfonyl)-l,2-dihydro-l,2,4,5-tetrazine (79) (79BCJ483). 3,6-Disubstituted hexahydro-1,2,4,5-tetrazines (132) afforded aldehyde hydrazones (133) when heated at their melting point (63AG1204). 

Furthermore, direct halogenation sometimes leads to substitution in the C-residue of the aldehyde hydrazone. For example, hydrazonoyl bromide 28c was obtained by direct bromination of hydrazone 58a or 58b (75CJC1484). Electron-withdrawing substituents in the N-aryl moiety of the arylhydrazone derivatives of heterocyclic aldehydes inhibit ring bromi-... 

The synthetic and spectral details to the P-dendrimers up through the third generation from a cyclotriphosphazene core (N3P3(OC6H4CHO)6) 116,1171 possessing six formyl moieties have also recently been reported. 118 The simple procedures lead to a spherical surface with electrophilic or nucleophilic reactive moieties, such as aldehydes, hydrazones, and aminophosphines. 

Variations to the radical acceptor component were also examined with a series of aldehyde hydrazones (Table 3, entries 7-15) [48]. Branching at a saturated a-carbon diminished the yields (entries 7-10), but the aromatic hydrazone 7 allowed successful radical addition (entries 11-14). The reactions were generally quite clean with the exception of 8a, which decomposed under these conditions (entry 15). It should be noted that low yields were accompanied by unreacted hydrazones 80-90% mass balance was generally observed. 

The addition of HMPA was found to be crucial for efficient cyclisation, as intermolecular pinacol coupling proved to be the major pathway when the aldehyde hydrazone was subjected to Sml2 alone. Skrydstrup proposed that a... 

Enders and coworicers have shown that deprotonation of chiral SAMP/RAMP hydrazones (or their substituted analogs) derived from ketones or aldehydes, followed by reaction with Davis oxaziridine reagent provides the a-hydroxy hydrazones in moderate yield but with high diastereoselectivity. Direct unmasking or protection followed by unmasking provides the corresponding a-hydroxy ketones or aldehydes respectively (Scheme 24). Both antipodes of the hydroxylated compounds are available by appropriate choice of (5)- or (R)-proline-deiived auxiliaries. The direction of induction is predictable, if not wholly uniform (R substitution alters the a-stereochemistry for aldehyde hydrazones). The process clearly provides a valuable approach to both systems. 

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