Hydrazones, phosphorylation

The mass spectra of cyclic phosphonate esters (114) and new 3-methyl-2(3H)-benzoxazolone hydrazone phosphorylated compounds and substi-... 

In the search for biologically active compounds a method was proposed [143] for the synthesis of phosphorus-containing hydrazones of 3-formylindole 147. Here hydrazides of diphenylphosphorylcarboxylic acids, which possess high biological activity [144], were used as phosphorylating agents. 

The cyclization of the phosphorylated arylhydrazones, leading to compounds 168, presumably takes place through the initial formation of 3-phosphorylated indoles 69, which isomerize to compounds 168 in the course of the reaction. Such 3—>2 rearrangements are well-known [30, 180-182, 231]. The transposition of the phosphorus-containing substituent in indoles was first observed in [178, 179]. In the review [8] the data on the formation of 2-phosphorylindoles from the arylhydrazones of phosphorylpropionic aldehyde were considered proved, but the results on the cyclization of hydrazones of phosphorylacetaldehyde to the 2-isomers were placed under some doubt. 

The reaction of lactim ethers with hydrazine and its derivatives proceeds readily. The resulting compounds are highly reactive and can be used in different reactions involving the side chain and the cyclic nitrogen atom.5,54,76> 80-82 For example, the treatment of caprolactam hydrazone (40) with nitrous acid results in pentamethyl-enetetrazole (41),54,80,81 and the use of diiferent lactim ethers gives other tetrazoles.32,35 The synthesis of polymethylenetetrazoles from lactim ethers and HN3,83 and also84 from HN3 and O-acyl lactims (or imidochlorides of lactams), obtained from lactams and sulfochlorides or phosphoryl chloride, may be mentioned. 

Structure-Activity Correlations of Acaricidal Hydrazones—Uncouplers of Oxidative Phosphorylation... 

Figure 2) (8). These compounds are generally much less toxic to mammals and less phytotoxic than the related dicyanocarbonylphenylhydra-zones investigated by DuPont workers several years ago (9). Some of our hydrazones (Figure 2) show interesting insecticidal and acaricidal properties (not discussed in detail here). Many are potent uncouplers of oxidative phosphorylation in rat liver mitochondria. 

The versatility of this reaction is increased when a substituted hydrazine is used instead of the primary amine, providing ready access to 1-aminoimidazoles (11) (R = NHR) from the hydrazones [36]. Hydroxylamine converts the o -(acylamino)ketones into oximes. In the presence of phosphoryl chloride or the fluoride ion, imidazole A -oxides can be generated. Thus, 2-formyl-4-methyl-l-phenylimidazole 3-oxide has been made in around 50%... 

If one looks at a complex correlation such as eq 11 (9, 1 ) for uncoupling oxidative phosphorylation by a-cyano-a-acylcarbonyl phenyl hydrazones (1), one has an impossible task to try to discern what part of the electronic effects relates to distribution and what part, if any, to mechanism. 

Solvents are commonly dimethylformamide, a chloroalkane or chloroalkene (methylene chloride, chloroform, 1,2-dichloroethane, etc.) or phosphoryl chloride. Temperatures used are generally in the range CM00 C.la Substrates include activated aromatic or heteroaromatic compounds, alkenes (including enamines and enol derivatives), methyl or methylene ketones and "active methyl or methylene groups in general, and hydrazones, azines and aliphatic diazo compounds. 

In a reaction similar to the formation of theophyllines (32 - 33), uracil-6-yl hydrazones are transformed into triazolouracils by the action of N-nitro-sodimethylamine and phosphoryl chloride in refluxing benzene (Scheme 15).4 ... 

Hydrazone von / -Phosphono- und /i-Phosphinyl-ketonen reagieren mit Triethoxy-methan (0,01 mol Hydrazon/0,05 mol mit Triethoxy-methan/0,5 ml Essigsaure) zu 4-Phosphoryl-bzw. 4-Phosphinyl-lH-pyrazolen754-756. 

Preparative studies have been reported on the phosphorylation of a series of hydrazines and hydrazones and on the phosphorylation of vicinal diamines with diphenyl phosphorochloridate. The cyclic phosphoramidate esters (12) and (13) may be obtained by treatment of the appropriate acyclic... 

The field of acylphosphonates (a-ketophosphonates) has been reviewed previously This chapter will deal mostly with the advances made since the publication of the previous review however, results from the older literature will be included for completeness. This chapter includes functional derivatives of both the phosphoryl and the carbonyl groups. With regard to the phosphoryl group, this refers to acylphosphonic acids esterified to various degrees, and also to acylphosphonoamidates and to acylphosphonic mono-and dihalides. With respect to the carbonyl group, this refers mainly to enolates, enamines, oximes and hydrazones in which the closeness of the phosphoryl function has yielded a wealth of recent results. These are discussed separately in Sections II and IV. 

Phosphinic hydrazides react with ketones to produce hydrazones (7.220). Phosphoric hydrazides will phosphorylate phosphate anions to give pyrophosphates (7.221). 

Also interesting in the field of physiologically active substances are phosphorylated imidazoles 1640. These can be prepared from an isocyanide intermediate 1639 with primary amines, while reaction of the isocyanide with hydrazonic acid yields phosphorylated tetrazole 1641. The phosphorylated isocyanide 1639 is obtained by dehydration of the corresponding formamide 1637 with phosphorus pentachloride via an imine intermediate 1638 [1222]. 

Dehydration of the oximes of (all- )-retinaldehyde (2) with phosphoryl chloride (Henbest et aL, 1955), trifluoroacetic anhydride (Carotti and Campagna, 1979), or selenium dioxide (Sosnovsky et al., 1979) gave retinonitrile (156), and this compound was also obtained by the fragmentation of the quaternary hydrazone (605) (Dawson a/., 1980). 

DAB 155a-c and 2,3-DAN 235 on the terminal carbon of the heterodiene system of 1,2-diaza-l,3-butadienes 246 with the formation of the hydrazone 1,4-adduct (Michael type) 250. The subsequent nucleophilic attack of the second amino group at the hydrazone carbon with the loss of a hydrazine carboxylate residue results in 2-phosphorylated quinoxalines 251a-i. This strategy affords a very efficient entry to quinoxaline phosphine oxides 251a, c, e-h and phosphonates 251b,... 

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