Synthesis And Bioactivity Of Novel Camphoric Acid Derivatives

Camphor is a nonwood forest product with bicyclic monoterpene structure. As a natural and preponderant resource of China, it can also be synthesized via several reaction steps from a-pinene which is the dominant component of turpentine. Camphor itself exhibits a wide range of bioactivities. Camphoric acid, the oxidation product of camphor, and its derivatives have been found to show various bioactivities. In this thesis, camphoric anhydride was prepared by using camphoric acid as starting material and acetic anhydride as dehydrating agent. Then, four types of novel camphoric acid derivatives with potential bioactivity were designed and synthesized by building a bridge with hydrazine or ethyienediamine molecule, and by introducing of acylhydrazone, thiourea, sulfonamide and diacylhydrazine groups into the molecular skeleton of camphoric acid. This research aims at providing a new way for the deep development and utilization of camphoric acid.In this thesis, forty-nine novel camphoric acid derivatives were synthesized using camphoric acid as starting material. The synthetic conditions were investigated preliminarily. The novel compounds were characterized by means of FT-IR,'H NMR,13C NMR, ESI-MS, HSQC and NOESY techniques. Furthermore, fungicidal and herbicidal bioactivities were evaluated for the target compounds. The main research contens and results are shown as follows:1. Camphoric anhydride was prepared by using camphoric acid as starting material and acetic anhydride as dehydrating agent. Then, N-amino camphorimide was prepared by the N-acylation reaction of camphoric anhydride with hydrazine hydrate, followed by the condensation reaction of N-amino camphorimide with substituted phenyl aldehydes in the presence of glacial acetic acid as catalyst and under microwave irradiation to afford eighteen novel camphoric acid-based acylhydrazone compounds4a-4r.2. Camphoric anhydride was prepared by using camphoric acid as starting material and acetic anhydride as dehydrating agent. Then, aminoethyl substituted phenyl thioureas were synthesized by the reaction of ethylenediamine with substituted phenyl isothiocyanides which were converted from the corresponding substituted anilines, followed by the reaction of camphoric anhydride with aminoethyl substituted phenyl thioureas to yield ten novel camphoric acid-based thiourea compounds7a-7j.3. Camphoric anhydride was prepared by using camphoric acid as starting material and acetic anhydride as dehydrating agent. Then, N-aryl sulfonyl ethyenediamines were synthesized by the reaction of ethylenediamine with substituted benzenesulfonyl chlorides, followed by the reaction of camphoric anhydride with N-aryl sulfonyl ethyenediamines to obtain eleven novel camphoric acid-based benzene-sulfonamide compounds9a-9k.4. Camphoric anhydride was prepared by using camphoric acid as starting material and acetic anhydride as dehydrating agent. Then, ten novel camphoric acid-based diacylhydrazine compounds10a-10j were synthesized by the N-acylation reaction of camphoric anhydride with aryl acylhydrazines.5. The fungicidal activity of all the target compounds was evaluated by disc method in vitro. It was found that, at the concentration of50mg·L-1, sixteen target compounds, including camphoric acid-based acylhydrazone compounds 4f (R=o-Br),4g (R=p-Br),4m (R=p-OCH3),4p (R=p-OH),4a (R=H),4h (R=o-NO2),4i (R=m-NO2),4k (R=o-OCH3), and4n (R=o-OH), camphoric acid-based benzenesulfonamide compounds9a (R=H) and9e (R=m-OCH3), camphoric acid-based diacylhydrazine compounds10h (R=?-Pyridyl),10b (R=p-NO2Ph),10i (R=y-Pyridyl),10a (R=Ph), and10g (R=p-FPh), exhibited prominent inhibition activity against Physalospora piricola, which had inhibition rates of?90.0%. Camphoric acid-based thiourea compounds7c (R=o-OCH3),7d (R=m-OCH3) and9h (R=p-Cl) showed good inhibition activity against Alternaria solani, and had inhibition rate of86.9%. Camphoric acid-based acylhydrazone compounds4k (R=o-OCH3),4a (R=H) and4h (R=o-NO2) displayed good inhibition activity against Gibberella zeaey and had inhibition rates of80%?85%of86.9%. The other target compounds did not show obvious inhibition activity against the five tested fungi.6. The herbicidal activity of all the target compounds was evaluated by rape petri dish method and barnyard grass beaker method. It was found that, at the concentration of100mg·L-1, camphoric acid-based acylhydrazone compounds4j (R=p-Br),4r (R=p-Cl), and the intermediate2exhibited good growth inhibition activity against root of rape (Brassica campestris), and had inhibition rates of91.6%,91.4%, and86.8%, respectively. The other target compounds did not show obvious growth inhibition activity against root of rape (Brassica campestris). All the target compounds only displayed weak growth inhibition activity against barnyard grass (Echinochloa crusgalli (L.)).