Publisher Summary Tetrazole itself exhibits no pharmacological activity; however, many of its derivatives possess interesting biological actions. The tetrazole function is metabolically stable and this feature and a close similarity between the acidic character of the tetrazole group and the carboxylic group have inspired syntheses of potential medicinal agents. This chapter discusses the literature on the medicinal chemistry of tetrazoles. The most successful drug among the CNS acting tetrazole derivatives has been leptazol. The tetrazole system is metabolically stable and it may be of interest to introduce this stable lump on biologically active moieties and examine the effect produced on the activity. There are several instances of introduction of tetrazole heterocycle in the synthesis of new medicinal agents. A particular mention has been made of the promising anti-bacterial cephalosporin derivatives cephazolin sodium, ceftezole, and cephamandole.

Medicinal chemistry of tetrazoles.

The present invention relates to substituted 2-[2-halogenalkyl-4-(phenoxy)-phenyl]-l-[1,2,4]triazol-1-yl-ethanol compounds of formula (I) as defined in the description, and the N-oxides, and salts thereof, their preparation and intermediates for preparing them. The invention also relates to the use of these compounds for combating harmful fungi and seed coated with at least one such compound and also to compositions comprising at least one such compound. Formula (I) wherein: R is C1-C2-halogenalkyl, the other variables are as defined in the claims.

Fungicidal substituted 2-[2-halogenalkyl-4-(phenoxy)-phenyl]-1-[1,2,4]triazol-1-yl-ethanol compounds

Alkyl and aryl phosphites and phosphines react with compounds having weak heteroatom–heteroatom bonds, such as SS, OO, etc., and with azo compounds to form reactive phosphonium salts. These phosphonium salts in turn promote “redox” condensation reactions with compounds having active hydrogens. The condensation reaction of alcohols using the redox couple of a triaryl- or trialkylphosphine and a dialkyl azodicarboxylate has become known as the Mitsunobu reaction, based on his pioneering work in the late 1960s. The overall reaction is summarized, wherein the alcohol (R1OH) and acidic compound (H–Nu) are condensed to form product (R1–Nu), while triphenylphosphine is oxidized to triphenylphosphine oxide and the azodicarboxylate is reduced to the hydrazine. Although the typical redox combination is diethyl azodicarboxylate (DEAD) and triphenylphosphine, many other combinations have found selected use. The reaction is generally limited to primary and secondary alcohols, although tertiary alcohols react in a few intramolecular and intermolecular reactions. For secondary alcohols the reaction usually proceeds with clean inversion of stereochemistry. The acidic component of the reaction generally has an aqueous pKa < 15, with intramolecular reactions providing the exceptions. Examples of H–Nu include oxygen nucleophiles such as carboxylic acids and phenols; nitrogen nucleophiles such as imides, hydroxamates, and heterocycles; sulfur nucleophiles such as thiols and thioamides; and carbon nucleophiles such as β-ketoesters.



Major reviews of the Mitsunobu reaction were published in 1981 by Mitsunobu and in 1983 by Castro. The former review concentrated on reactions using DEAD/triphenylphosphine, while the latter review focused on reactions in which halogens replaced the hydroxy group using reagents such as triphenylphosphine/carbon tetrachloride, triphenyl phosphite/iodomethane, and triphenylphosphine/N-halosuccinimide. Reactions involving the DEAD/triphenylphosphine redox system are the principal subject of this chapter, with emphasis on the literature between 1981 and 1988.


Keywords:

Mitsunobu reaction;
adduct formation;
alcohol activation;
SN2 reaction;
mechanisms;
carbon–oxygen bond;
carbon–nitrogen bond;
carbon–sulfur bond;
carbon–halogen bond;
carbon–carbon bond;
ambident nucleophiles;
dehydration;
alkenes;
method comparison;
ester formation;
lactone formation;
akyl aryl ether;
epoxides;
dialkyl ethers;
enol ethers;
dialkyl ethers;
imides;
azides;
experimental procedures;
scope;
limitations

The Mitsunobu Reaction

The present invention relates to N-thioanthranilamide compounds of formula (I), and the stereoisomers, N-oxides and agriculturally or veterinarily acceptable salts thereof, wherein the substituents are as defined in the description. The present invention further relates to a method for combating or controlling invertebrate pests, to a method for protecting plant propagation material and/or the plants which grow therefrom, to plant propagation material comprising at least one compound according to the present invention, to a method for treating or protecting an animal from infestation or infection by parasites, to a process for the preparation of a composition for treating infested or infected animals and/or for protecting animals against infestation or infection by parasites, and to a compound according to the invention for use as a medicament.

N-thio-anthranilamide compounds and their use as pesticides

Malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. We previously reported identification of a new class of triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. Active compounds from the series contained a triazolopyrimidine ring attached to an aromatic group through a bridging nitrogen atom. Herein, we describe systematic efforts to optimize the aromatic functionality with the goal of improving potency and in vivo properties of compounds from the series. These studies led to the identification of two new substituted aniline moieties (4-SF5-Ph and 3,5-Di-F-4-CF3-Ph), which, when coupled to the triazolopyrimidine ring, showed good plasma exposure and better efficacy in the Plasmodium berghei mouse ...

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Lead-optimization of aryl and aralkyl amine based triazolopyrimidine inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice

Novel 1-substituted -2-imidazolyl (or 1,2,3-triazolyl)cyclohexanols or cycloheptanols having anti-fungal activity against wide range of agricultural fungi with vapor effect

Azolyl cycloalkanol derivatives and agricultural fungicides

A series of 4-aminomethyl-2, 3, 4, 9-tetrahydrothiopyrano [2, 3-b] indole derivatives was synthesized and evaluated for analgesic activity. Preliminary structure-activity relationship analysis showed that substitution on the benzene portion of the indole ring reduced the analgesic activity, whereas a short-chain Nb-alkyl substituent enhanced the potency, as exemplified by an Nb-methyl substituted analogue. This compound was equipotent to morphine in the acetic acid writhing assay using mice.

Studies on fused indoles. II. Structural modifications and analgesic activity of 4-aminomethyltetrahydrothiopyrano[2,3-b]indoles.

Two novel and simple methods for preparing 4-aminomethyl-2, 3, 4, 9-tetrahydrothiopyrano [2, 3-b] indoles are described. Both involve thio-Claisen rearrangements of indol-2-yl propargyl sulfides as a key step which affords thiopyrano [2, 3-b] indoles in good yields. Elaboration of these compounds led to fused tryptamine analogues which were found to have strong analgesic activity. The mechanism of this novel rearrangement is discussed.

Studies on Fused Indoles. I. Novel Synthesis of 4-Aminomethyltetrahydrothiopyrano [2, 3-b] indoles through a Thio-Claisen Rearrangement

Condensation of 1, 3-dicarbonyl compounds with 5-aminopyrazole (III) and its 3-carboxylic ester (X) was examined and several kinds of 5, 7-disubstituted pyrazolo [1, 5-a]-pyrimidines were obtained. It was observed by the infrared spectrum that the hydroxyl group at 5- and 7-positions of pyrazolo [1, 5-a] pyrimidine ring shows the lactam form in the neutral medium

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Yasuo Makisumi

Papers

Azolyl cycloalkanol derivatives and agricultural fungicides

Studies on fused indoles. II. Structural modifications and analgesic activity of 4-aminomethyltetrahydrothiopyrano[2,3-b]indoles.

Studies on Fused Indoles. I. Novel Synthesis of 4-Aminomethyltetrahydrothiopyrano [2, 3-b] indoles through a Thio-Claisen Rearrangement

Studies on the Azaindolizine Compounds. X. Synthesis of 5, 7-Disubstituted Pyrazolo [1, 5- a ] pyrimidines

Synthesis of Potential Anticancer Agents. IV. 5, 7-Disubstituted s-Triazolo [2, 3-a] pyrimidines.