Methoprene hydrolysis

Methoprene is an insect growth regulator and it is also used as an insecticide for cockroaches. The enantioselective isomerization of 7-methoxygeranylamine in the presence of [Rh((+)-BINAP)2]+ followed by acid hydrolysis provides the intermediate, 7-methoxycitronellal, in high yield with high optical purity (97%, 98% ee, Scheme 6).9 Alternatively, methoxylation of ( -citronellalenamine (98% ee) with methanol in the presence of 97% sulfuric acid followed by hydrolysis gives 7-methoxycitronellal in 79% yield without racemiza-tion (Scheme 6).9... 

Hydrolysis. Aqueous solutions of methoprene (0.5 ppm) were found to be totally stable to hydrolysis for four weeks at pH 5,... 

A water soluble activated ester of methoprene (Figure 5, Structure 16) was also prepared from sodium l-hydroxy-2-nitro-4-benzene sulfonate (16). The amount of compund 16 in crude preparations which contained both compound 16 and the free dianion (Figure 5, Structure 17) was determined by spectrophotometry in aqueous solution. Upon hydrolysis compound 16 yielded the dianion (Structure 17) which absorbed visible light at 406 nm in the presence of nucleophiles (Figure 5). Two absorbance readings were required to determine the amount of compound 16 present in the crude material. 

The first reading (A406) measured the amount of free dianion in the mixture. Hydroxide was then added to completely hydrolyze compound 16 to its acid (Figure 5, Structure 13) and the dianion, and a second reading was taken (A.qa(NaOH)). This determined the amount of dianion liberated by the hydrolysis of this activated ester of methoprene. The percent total ester in the crude mixture was calculated using Equation 1. 

Figure 5. Hydrolysis reaction of HNSA-ester (Structure 16) with base gave methoprene-spacer acid (Structure 13) and the dianion (Structure 17). The spectrum shows the absorbance of the dianion before ( ) and after hydrolysis (o).

An interesting application of this assay revealed that although the insect growth regulator S-methoprene had relatively high values for 96-h LC50 and 96-h EC50, the values for metabolites produced by photolysis and hydrolysis were lower (La Clair et al. 1998) in particular those in which hydrolysis of the ester had occurred displayed serious eye deformations. 

The synthetic conqround methoprene possesses all of these desirable features. Its synthesis utilizes several reactions we have studied, including ox3mercuration-demCTcuration to give the tertiary methyl ether, ester hydrolysis (Section 8-5), and PCC oxidation of a primary alcohol to produce an aldehyde (Section 8-6). 

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