Alkylation aromatic hydrazone

Hydrazinopyridazines are easily formylated with formic acid or ethyl formate and acety-lated with acetic anhydride. A-Pyridazinylthiosemicarbazides are obtained from thiocyanates or alkyl- and aryl-isothiocyanates. Hydrazinopyridazines condense with aliphatic and aromatic aldehydes and ketones to give hydrazones. 

Benzothiazoline, N-methyl-2-methylene-structure, 6, 238 Benzothiazolines aromatization, 6, 270 oxidation, 6, 272 structure, 6, 238 synthesis, 6, 323, 325 Benzothiazoline-2-thione, 3-methyl-in organic synthesis, 6, 329 Benzothiazoline-2(3 f/)-thiones tautomerism, 6, 248 Benzothiazolin-2-one alkylation, 6, 286 Benzothiazolin-2-one, 3-methyl-hydrazone... 

An example of the reaction of hydrazones with enynes is reported in a German patent (91GEP4001600). The alkynylpyrazoles were prepared by treating of RNHN=CR C02R2 with CH2=CR 0R" (R =C1, Br R = alkyl) followed by aromatization with acid (Scheme 26). 

Unsubstituted hydrazones of aromatic ketones and aldehydes have been converted in high yield to alkyl chlorides under Swern oxidation conditions, although the substrate actually undergoes a net reduction.93 When the hydrazone is dideuterated, a deuterium ends up on the carbon, supporting the proposed intermediacy of cation (34), which tautomerizes and loses N2, to give a carbocation which combines with the chloride. 

The unsubstituted hydrazones derived from aromatic ketones and aldehydes are converted to the corresponding alkyl chlorides, in high yield, under Swern oxidation conditions. In this unusual oxidation/reduction sequence, the substrate undergoes a net reduction. Unsubstituted hydrazones derived from cyclohexyl ketones yielded elimination products. The mechanism in Scheme 7 has been postulated.111... 

Treatment of aromatic carboxaldehyde (diaminomethylene)hydrazones (105) with hot acetic anhydride or benzoyl chloride affords l,4-diacyl-3-acylamino-5-ary 1-4,5-dihydro- 1H-1,2,4-traizoles (106) in 75-95% yields. In contrast, when the 4-pyridine analog of 105 was employed, the unusual hemianimal triazole derivative (107) was obtained. The structures of the novel compounds were determined by spectral methods and in several cases by x-ray structural analysis. Mechanistic considerations are discussed [95M733]. The oxazole-1,2,4-triazole (108) was prepared by cyclization of the corresponding oxazolecarbonyl-thiosemicarbazide with bicarbonate, alkylation at the sulfur and oxidation to the sulfoxide with MCPBA [95JHC1235]. 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

Furthermore, iminyl radicals, which are supposed to be intermediates in the annulations discussed above (see 32), have been directly generated from the corresponding oximes [56] or hydrazones [57] and applied in the intramolecular homolytic aromatic substitution. The intramolecular radical alkylation of arenes [58] and heteroarenes [59-62] was investigated by various research groups. As for the aryl radicals, the alkyl radicals used in these reactions are generally generated from the... 

As base. Numerous reactions that are initiated by deprotonation have been conducted with KF-AI2O3. These include the synthesis of diaryl ethers, amines, and sulfides by nucleophilic aromatic substitutions, AJ-alkylation of 2,4-dinitrophenyl-hydrazones, condensation of 3-phenylisoxazol-5-one with aldehydes, and ring closure of /V-(w-chloroalkyl) carboxamides to afford 1,3-oxazolines and 1,3-oxazines. ... 

Mercapto pyrimidines 82 were synthesized from acetoacetanilide, dihydroxybenzaldehyde, and thiourea, which were readily alkylated with benzyl chloride to afford 2-benzylthio derivatives 83 (Scheme 32). 83 when reacted with different amines in acetic acid furnished 2-amino derivatives 84 (R = Ar), whereas upon reaction with hydrazine hydrate 83 afforded 2-hydrazinyl derivative 84 (R = NH2), which with different aldehydes gave hydrazones 85 (R = 2-furyl, 2-thienyl). Arylidene thiazolidinone 86 was obtained from 84 with carbon disulfide, monochloroacetic acid, and aryl aldehydes, while 84 with ethyl acetoacetate and different aromatic aldehydes provided pyrazoles 87 (Scheme 32) (10MI9). Such tetrasubstituted pyrimidines act as cyclin-dependent kinase (CDK2) inhibitors. 

Mechanosynthesis was also used by Lamaty et al. to prepare a set of Boc-, Bz-, Fmoc-, and tosyl-hydrazones 68 from aldehydes by employment of Retsch MM200 mill (5mL stainless steel jar, 2x5mm balls). Aromatic, heteroaromatic, and alkyl aldehydes readily reacted under solvent-free conditions with stoichiometric amounts of hydrazines obtaining products quantitatively (selected results are given in Scheme 3.17) [15]. When the reaction was complete, the product was recovered as a solid directly in the jar and dried. The mechanochemical activation was shown to be essential to obtain a... 

Allenic hydrazones undergo a gold(I)-catalyzed cycloisomerization to substituted pyrroles, which are obtained with excellent yield (Scheme 4-60). This transformation requires heating of the allene with PhaPAuNTf-toluene complex in dichloromethane to 100 °C for 20 min. A 1,2-alkyl or aryl shift is key to the formation of the aromatic heterocycle. 

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