Diacylhydrazines

Diacylhydrazine insecticides are all derivatives of hydrazine (H2N-NH2). The following compounds are essentially nontoxic to mammals, their oral LD50 s in rats being 5000 mg/kg. 

Tebufenozide is effective against lepidopterous insects. Halofenozide is used for control of grubs and other soilborne turf pests. Methoxy fenozide is used for control of a broad range of lepidopterous larvae. Chromafenozide is used for control of lepidopterous larvae. 

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Diacylhydrazines (32) on heating with a primary amine undergo cyclization to the 1,2,4-triazole derivative (38). It is assumed that the amidrazone (37) is an intermediate in the reaction. Most practical syntheses of 1,2,4-triazoles now utilize an amidrazone or a derivative of this alicyclic intermediate containing three nitrogen atoms, and these variations are discussed in Chapter 4.12. 

Hydrazides (RCONHNH2) are highly useful starting materials and intermediates in the synthesis of heterocyclic molecules.2 They can be synthesized by hydrazinolysis of amides, esters and thioesters.3 The reaction of hydrazine with acyl chlorides or anhydrides is also well known,4 but it is complicated by the formation of 1,2-diacylhydrazines, and often requires the use of anhydrous hydrazine which presents a high thermal hazard. Diacylation products predominate when hydrazine reacts with low molecular weight aliphatic acyl chlorides, which makes the reaction impractical for preparatory purposes.5... 

In order to activate the 1,2-diacylhydrazines towards cychzation, they were reacted with tosyl chloride (Scheme 8). While the reaction with tosyl chloride alone did not afford any of the desired product, and the cychzation in the presence of strong bases, although successful, posed the same problems of removal, excellent results were obtained in the presence of both tosyl chloride and a supported strong base, with polymer-bound BEMP giving better results than polymer-supported l,3,4,6,7,8-hexahydro-l-methyl-2H-... 

N,N-Diacylhydrazines have been shown to yield 2,5-disubstituted-1,3,4-thiadiazoles and 5-phenyl-l,3,4-thiadiazole-2(3H)-thiones in the case of N-acetyl-N -ethoxycarbonylhydrazine, the... 

In the preparation of novel 1,3,4-oxadiazoles 56 from 1,2-diacylhydrazines 55, Brain and coworkers [29] used a highly efficient cydodehydration assisted by use of micro-waves, in THF as solvent, using polymer-supported Burgess reagent (Scheme 8.21). 

For convenience, the syntheses discussed in this section are divided into groups, depending on the structures of the starting materials, despite the fact that all of them contain C-N-N-C-O fragments. Therefore, 1,2-diacylhydrazines 109 are described as O-C-N-N-C-O components, acylhydrazones 110 as C-C-N-N-C-O components, while, for example, dithioates and similar compounds 111 are treated as S-C-N-N-C-O components. 

Table 5 Preparation of 1,3,4-thiadiazoles from diformyl- and diacylhydrazines and a sulfur source R1 R2 Conditions Yield 137 (%) Reference...

The pyrrolo[l,2-4][l,2,4]triazinone skeleton 76 was also accessible in quantitative yield through a triflic acid-catalyzed heterocyclization of trisilylated diacylhydrazines 75 derived from pyroglutamic acid (Equation 10) <1996JHC1073>. 

Diazomethane is also produced in the reaction of acylhydrazines with dichloro-carbene, but the process is less efficient, as only one equivalent of diazomethane is produced from two equivalents of the acylhydrazine. However, the procedure provides a useful route to symmetrical AUV -diacylhydrazines (Scheme 7.25) [11],... 

The dehydration of A,A -diacylhydrazines is a standard method for the formation of the 1,3,4-oxadiazole ring. 2,5-Dipicryl-l,3,4-oxadiazole (DPO) (19) is synthesized by treating 2,4,6-trinitrobenzoic acid (17) with phosphorous pentachloride, followed by treatment with hydrazine to give the A, A -diacylhydrazine (18) which undergoes dehydration on further reaction with phosphorous pentachloride in 1,2-dichloroethane. DPO exhibits high thermal stability but is very sensitive to impact and shock, making it useful in detonation transfer compositions. 

The malonate derivative (93) reacted with acylhydrazine (94) to give a mixture of diacylhydrazine monoenamine (95) and oxadiazole (88c), (Scheme 6) which was also formed from (95) on heating <88LA909). 

No important new general routes to 1,3,4-oxadiazoles have been reported since the mid-1980s. The major routes (as emphasized in both CHEC-I, and in the preceding two sections, 4.06.9.1 and 4.06.9.2) are (i) the formation of oxadiazoles by cyclodehydration of diacylhydrazines... 

An analogous meso-ionic l,3,4-oxadiazol-2-ene (168) in which the negative charge is associated with a fluorenyl residue has also been recently described. The A, iV -diacylhydrazine (166) and acetic... 

Primary, secondary and tertiary thioamides and thionreas are readily converted to their corresponding 0x0 analogs with Oxone in refinxing CH3CN . Thiono esters were converted to esters, while thioketones remained intact nnder these reaction conditions. Hydrazines can be selectively converted to esters and acids in high yields by nsing Oxone in an alcohol and a water, respectively . However, Mane and coworkers showed that hydrazides can be smoothly converted into the corresponding Af,Af -diacylhydrazines in excellent yields with Oxone in water (equation 67) . ... 

Reaction of 232 with 4-substituted l,3-oxazol-5(4/7)-one 247 led to diacylhydrazines 248 or to imidazole derivatives 249 depending on the reaction temperature (Scheme 24). l,2,4-Triazole-3-thione 250 was obtained by a two-step sequence from 232 with phenyl isothiocyanate and subsequent base-catalyzed cyclization of thiosemicarbazide 251. The effects of hydrazones 241-246 on inhibition of photosynthetic electron transport in spinach chloroplasts and chlorophyll content in the antialgal suspensions of Chlorella vulgaris were investigated <2005CEC622>. 

Azoalkanes have also been produced by oxidation with mercuric oxide. This reagent is considered the reagent of choice for azoalkanes [76, 87, 93], as well as for the preparation of cyclic azo compounds [94], and 1-pyrazolines [95a]. When used in the preparation of a-carbonyl azo compounds, evidently mercury complexes are formed with the diacylhydrazine starting materials. These complexes are then treated with halogens (iodine or chlorine) to produce the azo compounds [92]. 

Oxadiazoles have often attracted the attention of medicinal chemists as stable bioiso-steres of metabolically labile esters. 1,3,4-Oxadiazoles are generally prepared by cyclodehydration of 1,2-diacylhydrazines or their equivalents. Symmetrical 2,5-disubstituted examples were able to be rapidly prepared in a one-pot condensation-cyclodehydration of benzoic acids (2 equiv) with hydrazine dihydrochloride, in the presence of... 

In addition, thionation-cyclisation of 1,2-diacylhydrazines to 1,3,4-thiadiazoles has been achieved by the action of Lawesson s reagent under solvent-free microwave heating (Scheme 3.24)11. 

Brain, C.T., Paul, J.M., Loong, Y. and Oakley, P.J., Novel procedure for the synthesis of 1,3,4-oxadiazoles from 1,2-diacylhydrazines using polymer-supported Burgess reagent under microwave conditions, Tetrahedron Lett., 1999, 40, 3275. 

Acetamide derivatives of dibenzoxazepine 113 were prepared and amidated with different alkyl and aralkyl side chains in order to function as a potential surrogate for the diacylhydrazine group of SC-51089, a potent PGE2 antagonist (Figure 15) <1996JME609>. 

Reaction of a diacylhydrazine under nitrogen produced a gas pyrophoric at the vent to atmosphere. It is postulated that the hydrazine moiety reduced the phosphorus tribromide to a volatile phosphine. 

Sydnones 78 (R1 = Ph, Ar or 3-pyridyl, R3 = H or Me) are obtained from the nitrosoamino acids 77 and acetic anhydride under ultrasound (94MI153). Three examples of the formation of oxadiazoles by microwave irradiation are from O-acyl amide oximes 79 in the presence of aluminium oxide, from amide oximes 80 and isoprop-enyl acetate in the presence of KSF-clay and from N,N -diacylhydrazines 81 and thionyl chloride (95SC1451). 

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