Mosquito repellency data on acylpiperidines derived from the U.S. Department of Agriculture archives were modeled by using molecular descriptors calculated by CODESSA PRO software. An artificial neural network model was developed for the correlation of these archival results and used to predict the repellent activity of novel compounds of similar structures. A series of 34 promising N-acylpiperidine mosquito repellent candidates (4a-4q) were synthesized by reactions of acylbenzotriazoles 2a-2p with piperidines 3a-3f. Compounds (4a-4q) were screened as topically applied mosquito repellents by measuring the duration of repellency after application to cloth patches worn on the arms of human volunteers. Some compounds that were evaluated repelled mosquitoes as much as three times longer than N,N-diethyl-m-toluamide (DEET), the most widely used repellent throughout the world. The newly measured durations of repellency were used to obtain a superior correlation equation relating mosquito repellency to molecular structure.N-acylpiperidine ͉ quantitative structure-activity relationship ͉ CODESSA PRO ͉ artificial neural network ͉ Aedes aegypti

A c y l b e n z o t r i a z o l e s a s A d v a n t a g e o u s N -, C -, S -, a n d O -A c y l a t i n g A g e n t s Abstract: N-Acylbenzotriazoles are useful acylating agents, especially where the corresponding acid chlorides are unstable, difficult to prepare, or unknown. Reactions with N-acylbenzotriazoles offer efficient transformations under mild conditions, and provide an alternative convenient procedure for N-, C-, S-, and O-acylation. In this account, our work mainly carried out from 2000 to early 2005 is discussed.

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(Benzotriazol-1-yl)-1-phenoxyalkanes 10, prepared by two-step transformations of the corresponding aldehydes, are readily deprotonated at the methine group by BuLi. Subsequent reactions with alkyl halides, aldehydes, ketones, and imines yield the corresponding substituted derivatives that undergo hydrolysis under acidic conditions to afford the expected functionalized ketones 13, 15,17, 19, 21, 24, and25. Two successive lithiations of (benzotriazolyl)phenoxymethane, each followed by reaction with a trialkylsilyl chloride, alkyl halide, aldehyde, or ketone, generate similar intermediates 27, 29, 31,33, and 36. Subsequent hydrolyses of 27, 29, 31, 33, and 36 yield the functionalized ketones 28, 30, and 32 and the alkanoylsilanes 34 and 37 in good yields.

Acyl-, aroyl-, and heteroaroyl-acetic esters 6a-f and 8a-l are prepared by reactions of 1-acylbenzotriazoles 1a-k with acetoacetic esters 5 or 7a,b in the presence of sodium hydride followed by regioselective deacetylation. Similar C-acylation/deacetylation of acetylacetone and benzoylacetone affords beta-diketones 10a-d and 13a-c, respectively.

Novel and facile routes to alkenyl, alkynyl, and aryl 1,2-diketones utilize treatment of benzotriazole derivatives 1, 7a,b, and 15a − d with butyllithium and subsequent reaction with esters or acid chlorides to yield the substituted intermediates 2a − d, 8a,b, and 16a − g. Reactions of the deprotonated 1 and 7 with α,β-unsaturated aldehydes followed by oxidation also produces similar intermediates 5 and 11a,b. Subsequent hydrolyses of the intermediates of type 2, 5, 8, 11, and 16 afford diverse 1,2-diketones in good yields.

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.

Reactions of oximes 9, 17, and 19 with electrophiles 15a-f and 24 in the presence of anhydrous potassium carbonate or triethylamine give 2-substituted condensed ring oxazoles 10, 16a-c, 18a-d, 20a-c, and 25 in a new general route to these compounds.