Synthesis And Biological Activity Of Novel N-Tosyl Piperidinyl-Containing α-Aminophosphonates

Due to their diverse and interesting biological and biochemical properties, aminophosphonates areof considerable current interest. This class of compounds is mainly applied as plant growth regulators,herbicides, fungicidal, anti-plant virus, enzyme inhibitors and anti-cancer agents. Such an impressivearray of applications has recently stimulated a growing amount of research on the synthesis of-aminophosphonates and rendered the-aminophosphonate moiety the status of a novelpharmacophore in the context of drug design.N-tosyl piperidinyl-containing heterocycles are subunits of many biologically activepharmaceuticals and reported to exhibit a wide range of bioactivities, including nervous system agents,cardiovascular agents, antitumor, anti-infective, anti-inflammatory activities.Magnesium perchlorate showed to be very active in promoting a variety of reactions. In2007, itwas reported as an extremely efficient catalyst for the formation of-aminophosphonate by a one-pot,three-component reaction under solvent-free conditions. In this paper, magnesium perchlorate isexplored as catalyst and the reaction involving1-tosylpiperidine-4-one, aromatic amines with anelectron-donating or–withdrawing substituent, and diethyl phosphite are carried out under solvent-freeconditions. Thus, compounds1-6were synthesized and a single crystal structure of compound2a wasobtained. All the novel compounds were analyzed by IR,1H NMR,¹³C NMR,31P NMR and HRMSspectroscopy. Preliminary tests showed that some of these compounds, to some extent, have insecticidalactivities against Plutella xylostella, fungicidal activities against Phytophthora capsici, Botrytis cinerea,and Phomopsis asparagi （Sacc.） Bubak, no herbicidal activities against Abutilon theophrasti Medic,Amaranthus retroflexus L., Gramineae and Digitaria sanguinalis.Dichlorodiphenyltrichloroethanes （DDTs）, the sum of DDT related compounds （p,p’-DDT,o,p’-DDT, p,p’-DDE, o,p’-DDE, p,p’-DDD, and o,p’-DDD）, are among the substances restricted orbanned globally under the Stockholm Convention on Persistent Organic Pollutants.Labelled DDTs serve as internal standards for the confirmation and quantification of DDTs viamass spectrometry. So far, labelled DDTs have been extensively applied as a tracer in revealing theexposure of wildlife and humans to DDTs and its mode of action, metabolism, detoxificationmechanism, degradation, distribution, and potential for long-range transport of these chemicals.This paper describes an efficient synthesis of¹³C₁₂-labelled DDT, DDD and DDE from¹³C₆-benzene with63%,60%and60%overall isotopic yield, respectively. The¹³C₁₂-labelled p,p’-DDDwas a novel compound. The oxychlorination of benzene to chlorobenzene was first employed in thesynthesis of p,p’-DDT, p,p’-DDD and p,p’-DDE. These labelled compounds are useful as internalstandards in mass spectrometry for monitoring DDT and its metabolites DDD as well as DDE.