N- hydrazones

Imines and related compounds containing a carbon-nitrogen double bond C=N (hydrazones, acylhydrazones, oximes) present the very attractive feature of being double dynamic entities capable of undergoing both ... 

When ethyl acetoacetate is warmed with an equivalent quantity of phenyl-hydrazine, the compound (I), which is not a true hydrazone, is first formed this undergoes ring formation (II) with loss of ethyl alcohol upon further heating. The product (II) is N or l-phenyl-3-methyl-5-pyrazolone. 

Some examples of the use of a temporary additional site of coordination have been published. Burk and Feaster have transformed a series of ketones into hydrazones capable of chelating to a rhodium catalyst (Scheme 4.7). Upon coordination, enanti os elective hydrogenation of the hydrazone is feasible, yielding N-aroylhydrazines in up to 97% ee. Finally, the hydrazines were transformed into amines by treatment with Sml2. 

Agrochemical Products. Hydrazones of vanillin have been shown to have a herbicidal action similar to that of 2,4-D, and the zinc salts of dithiovanillic acid. Made by the reaction of vanillin and ammonium polysulfide in alcohoHc hydrochloric acid, dithiovanillic acid is a vulcanization inhibitor. 5-Hydroxymerciirivanillin, 5- a cetoxym erci iri va n ill in, and 5-ch1oromercurivani11in have been prepared and found to have disinfectant properties. 

Special reactions of hydrazides and azides are illustrated by the conversion of the hydrazide (205) into the azide (206) by nitrous acid (60JOC1950) and thence into the urethane (207) by ethanol (64FES(19)105Q) the conversion of the same azide (206) into the N-alkylamide (208) by ethylamine the formation of the hydrazone (209) from acetaldehyde and the hydrazide (205) and the IV-acylation of the hydrazide (205) to give, for example, the formylhydrazide (210) (65FES(20)259). It is evident that there is an isocyanate intermediate between (206) and (207) such compounds have been isolated sometimes, e.g. (211). Several of the above reactions are involved in some Curtius degradations. 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

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... 

Liquid paraffin d -3-ketosteroids (testosterone isonicotinic hydra-zone, testosterone dansyl hydrazone) > 10-fold dipping solution, 33% in n-hexane [232]... 

Liquid paraffin cortisol as dansyl hydrazone 10-fold dipping solution, 67% m n-hexane, serum investigations [248, 249]... 

According to a detailed mechanistic study, the first step is the abstraction of the relatively acidic hydrazone proton (93- 97). This is followed by hydride attack on the trigonal carbon of the C=N bond, mainly from the a-side at C-3, together with the concomitant loss of the tosylate anion (97 -> 98). Expulsion of nitrogen from the resulting intermediate (98) yields a fairly insoluble anion-metal complex (99) which upon decomposition with water provides the methylene derivative (100). 

A mechanism which is consistent with the various experimental results for olefin formation involves the initial abstraction of the hydrazone proton (103->106) In this case, however, expulsion of the tosylate anion is associated with the abstraction of a second hydrogen from C-16 instead of hydride attack on the C=N bond (compare 97 98 and 106 107). Ex-... 

Substituted aryl hydrazones can be converted to geminal difluondes in satis factory yields by molecular fluorine [H4, iodine fluoride [ 5], and N bromo-suc-cinimide-pyridinium polyhydrogen fluoride or A -bromosuccinimide-polyvi-nylpyridinium polyhvdrogen fluoride [5(5] (equation 21) (Table 6)... 

Iodine fluoride is a more versatile reagent than molecular fluorine in geminal fluorination of other hydrazones and related compounds under milder reaction conditions [55] Substrates fluorinated include hydrazones of simple cyclic or steroidal ketones (e g, 4 tert butylcyclohexanone, 70%, 3 cholestanone, 70%), W methyl and A/N dimethylhydrazones [R2C=NNH(CH3) 70%, R2C=NNC(CH3)2, 50%], semicarbazones (R2C=NNHCONH2, 25-50%), and 2,4-dinitrophenylhy-drazones [R2C==NNH-C6H3-2,4(N02)2, 25-50%]... 

The Hurd-Mori 1,2,3-thiadiazole synthesis is the reaction of thionyl chloride with the N-acylated or tosylated hydrazone derivatives 1 to provide the 1,2,3-thiadiazole 4 in one simple step. ... 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

To prepare fervenulin 4-oxides 12 or toxoflavine 4-oxides 146, it is convenient to use the reaction of l,3-dimethyl-2,4-dioxopyrimidin-6-yl hydrazone 147 or N-(3-methyl-2,4-dioxopyiimidin-6-yl) iV-methylhydrazone 148 with potassium nitrate in acetic acid [75CPB1885,76CPB338,76JCS(CC)658,82JHC1309,93CPB362]. Diethyl azodicarboxylate can be used instead of potassium nitrate [76JCS(P1 )713]. 

The phenylhydrazones of 2-[(2-alkenyl)amino]-3-formyl-4//-pyrido-[1,2-n]pyrimidin-4-ones 242 underwent a thermally induced intramolecular 1,3-dipolar cycloaddition leading to a mixture of tetracyclic compounds 243 and 244 at room temperature or to 244 under reflux (96T901). Derivatives 243 were not stable and converted to compounds 244 gradually on standing or on heating their ethanolic solutions in air. The ( )-hydrazones 245 could be isolated only in the case of... 

Analogously, the corresponding bcnzylidene hydrazones (2, R" — NH—N—CH—CcHg) could be prepared from the benzaldehyde selenosemicarbazone (cf. Table These react only as very... 

The free selenazole hydrazines are solids, sometimes well crystallized compounds. They show the typical properties of hydrazines. Thus they reduce Fehling s solution on warming and liberate silver, even in the cold, from ammoniacal silver nitrate solution. Further, they react with carbonyl compounds for example, benzylidene hydrazones are formed with benzaldehyde. These are identical with the hydrazones formed by direct condensation from benzaldehyde selenosemicarbazone and the corresponding a-halogenocarbonyl compound. 2-Hydrazino-4-phenylselenazole has also been reacted with acetophenone. The 2-a-methylbenzylidenehydrazone of 4-phenyl-selenazole (2, K = CJl, R" = H, R" = NH—N CMe-aH ) forms golden yellow plates mp 171°C. ... 

Alkylation of 737 with 738 gave 739 (81USP4252806). Reaction of 2-hydrazinoquinoline with the quaternary salts of N,N-substituted thioamides gave the hydrazones 735 whose cyclization in acetic acid gave triazoloquinolines 736 (80PJC661) (Scheme 127). 

Alternately, amifloxacin can be prepared via the ofloxacin/difloxacin route using an addition-elimination reaction with unsymmetiical N-methyl-N-formyl hydrazone to give 49 [14]. 

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