Proneonicotinoid

Abstract

Since the discovery of imidacloprid in 1986, various structural modifications have been attempted to devise molecules with favorable biological properties different from those of the first product. [1][2][3][4][5][6][7][8][9][10] A prodrug is a substance that has to be transformed in order to show or enhance activity or to lessen unfavorable properties of the original ingredient. 11) Drabek and Neumann 12) introduced the term proinsecticide for an insecticide by referring to the pharmaceutical term. This article addresses nine prodrug types of the neonicotinoid, using the term proneonicotinoid in this context. Oxadiazine and Related Cyclic AzinesAcetal, thioacetal and aminal have been frequently used as a protective group for aldehyde or ketone in synthetic chemistry. 13) The assembled framework regenerates the carbonyl group by hydrolysis after the task, leaving the individual protecting fragments (Eq. 1, Fig. 1). Oxadiazine (XϭO), thiadiazine (XϭS) or triazine (XϭNMe) structure (1), constructed by linking both the amine ends of original insecticidal molecule (2) with formaldehyde through the corresponding hetero fragment, can be viewed as a similar assembly. 14-16) The cleavage of thiamethoxam (3) into clothianidin (5) in insects and plant tissues has been reported. 17,18) Hydrolysis comparison of the three cyclic azines (1) to the corresponding diaminonitroimines (2) in a physiological salt solution showed that the half-lives of the oxadiazines were notably longer than the corresponding thiadiazines and triazines. We have attributed the stability of the oxadiazine framework to the relatively strong -NCH 2 -O-CH 2 N-linkage by comparing the bond energy for C-O of 85-91 kcal/mol with 61 kcal/mol for C-S and 69-75 kcal/mol for C-N. 19) Thus, the devised thiamethoxam displays several favorable profiles in field practice, 16) and its present sales volume worldwide ranks second in the neonicotinoid class. This prodrug development practice clearly shows that a small structural variant (only one atom in this case) leads to large differences in the success. Mannich BasesThe Mannich reaction is the condensation of a labile C-H bond with an aldehyde and a primary or secondary amine to form a so-called Mannich base. 20) This well-established synthetic protocol was applied to a proneonicotinoid construction (Eqs. 2-4, Fig. 2). 21,22) The Mannich bases (7a, b) derived from b ,b -diamino nitroethylene molecules (6a, b) can regenerate the parent component in an acidic milieu. The concentrations of Mannich bases (7a, b) to cause spontaneous neuroblocking in the excised central nerve cord of American cockroaches (Periplaneta americana L.) were 100-140 mM at the level of 140 mM of 3N-Me (6c) derivative, and far higher than the 1.6-1.9 mM of the starting molecules (6a, b). However, 24 hr after the injection the minimum lethal doses were ProneonicotinoidShinzo KAGABU* Department of Chemistry, Faculty of Education, Gifu University, Gifu 501-1193, Japan (Received January 5, 2011 Accepted February 18, 2011) Prodrug is a biologi...

CO2 and Formate Complexes of Phosphine/Borane Frustrated Lewis Pairs

“… Im Allgemeinen sind nicht‐cyclische Strukturen weniger lipophil als die entsprechenden fünf‐ und sechsgliedrigen Ringsysteme. Die Wasserlöslichkeit wird durch die funktionelle Gruppe [X‐Y] innerhalb der Pharmakophorgruppe [‐N‐C(E)X‐Y] beeinflusst und steigt in der Reihenfolge [N‐NO 2 ]<[N‐CN]<[CH‐NO 2 ]. Im Hinblick auf E steigt die Lipophilie in der Reihenfolge NH<O<C<S 22 …”

Propesticides and their use as agrochemicals

“…The agrochemical importance of synthetic competitive modulators selectively addressing the nicotinic acetylchloline receptors (nAChRs) located in the central nervous system of pest species is enormous and has been widely reviewed in numerous articles and book chapters over the past decade . Since the start of successful commercialisation of neonicotinoid AChR agonists, with the launch of imidacloprid in 1991, various structural modifications in this substance class, including proinsecticide design, have been carried out in an attempt to improve the biological profile and the physicochemical properties of the class …”

“…48 -50 Since the start of successful commercialisation of neonicotinoid AChR agonists, with the launch of imidacloprid in 1991, various structural modifications in this substance class, including proinsecticide design, have been carried out in an attempt to improve the biological profile and the physicochemical properties of the class. 51 to a cleavage (e.g. by bioactivation or oxidation) in insects and plant tissues to clothianidin without a six-membered ring (Fig.…”

Ethyl 2-{3-[(2-chloro-1,3-thiazol-5-yl)methyl]-4-nitroimino-1,3,5-triazinan-1-yl}acetate

“…For general background to neonicotinoid compounds and their application as insecticides, see: Kagabu (1996); Kagabu et al (2005); Tian et al (2007); Tomizawa et al (2000); Tomizawa & Yamamoto (1993); Zhang et al (2004). For halogen bonding, see: Riley & Merz (2007).…”