Synthesis Of Carbofuran Phenol, And The Synthesis, Characterization And Biological Activity Of Its Derivatives Containing N-arylthiazol-2-amine

Carbofuran phenol is an important intermediate in the synthesis of carbamates, such ascarbofuran, benfuracarb, carbosulfan and furathiocarb. However, the yield of cyclization islow and a large quantity of waste residue is generated during producing carbofuran phenol,and its derivatives such as carbofuran will be eliminated gradually as their high toxicity. Inorder to solve these problems, the research of this paper aimed at screening efficient catalystfor cyclization to improve the yield of carbofuran phenol, efficiently use of the by-productsgenerated from the reaction, design and synthesis a series of compounds from carbofuranphenol with the mind of complicating biological activity of carbofuran phenol andthiazol-2-amine to find new pesticides with efficient, broad-spectrum and low toxicity. Themain findings are as follows:Aluminum isopropoxide carboxylates were firstly used as new catalysts for thecyclization of carbofuran phenol. The effect of the type, the number of carboxylate in thealuminum isopropoxide carboxylate and the amount of the catalyst on the yield of carbofuranphenol was investigated, The possible mechanism of catalyzing2-（2-methylallyloxy） phenolto carbofuran phenol was explored as well. According to the possible reaction mechanism,series of aluminum isopropoxide dicarboxylate and aluminum phenolate diacetate werescreened as new catalysts. As a result of our research, aluminum isopropoxide diacetate,aluminum isopropoxide malonate and aluminum carbofuran phenolate diacetate are efficientcatalysts for synthesis of carbofuran phenol from2-（2-methylallyloxy）phenol, with thecarbofuran phenol yields were80.8%,80.9%and80.8%, respectively. The new catalysts arevaluable, and the preparation of the catalysts is convenient.During screening efficient catalysts for cyclization of carbofuran phenol, we havepurification and confirmed a variety of by-products by NMR and mass spectrometry:4-（2-methylallyl）benzene-1,2-diol,4-（2-methylprop-1-enyl）benzene-1,2-diol,2,2-dimethyl-4-（2-methylprop-1-enyl）-2,3-dihydrobenzofuran-7-ol and2,2,7,7-tetramethyl-2,3,6,7-tetrahydrobenzofuro[7,6-b]furan. The crystals of2,2,7,7-tetramethyl-2,3,6,7-tetrahydrobenzofuro-[7,6-b]furan suitable for X-ray structure determination were obtained by the slowlyevaporating an ethanol solution slowly, X-ray diffraction of the crystal shows that: the crystalis a monoclinic system, P21/n of space group, unit cell dimensions: a=0.87553（6） nm，b=0.60721（4） nm, c=2.32082（17） nm；β=92.1860（10）°; V=1.232.92（15） nm³, Z=4, Dc=1.176g/cm³, μ=0.077mm^-1, F（000）=472.According to the possible catalytic mechanism of synthesizing carbofuran phenol from2-（2-methylallyloxy）phenol in this paper,3,6-bis（2-methylallyl）benzene-1,2-diol wassynthesized from1,2-bis（2-methylallyloxy） benzene via Claisen rearrangement under catalyst and heating, the2-methylallyls and o-hydroxy groups of the compound could easily occurcyclization reaction to generate2,2,7,7-tetramethyl-2,3,6,7-tetrahydrobenzofuro[7,6-b] furanbecause the compound was instability in the catalyst and heating surroundings; carbofuranphenol was synthesized from2-（2-methylallyloxy） phenol via Claisen rearrangement andcyclization reaction, at the same time,4-（2-methylallyl）benzene-1,2-diol generated from2-（2-methylallyloxy） phenol via Claisen rearrangement and Cope rearrangement.The active phenolic hydroxyl group and allyl of4-（2-methylallyl）benzene-1,2-diol couldbe modified to synthesize of high added value fine chemical products: Veratraldehyde wassynthesized from the by-product via etherification, isomerization and ozonization; Heliotropinwas synthesized from the compound via methylene etherification, isomerization andozonization; Helional was synthesized from the by-product via methylene etherification,boron hydrogenated-oxidation, Corey-Kim oxidation.4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-5-alkyl-N-arylthiazol-2-amineswere synthesized from carbofuran phenol with the mind of complicating biological activity ofcarbofuran phenol and thiazol-2-amine. The synthesis method is simple and the synthesiscondition is mild, with yields of45.3⁵2.1%（calculated by carbofuran phenol）, thecompounds were confirmed by1H NMR, MS and elemental analysis.Biological assay:4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N-phenylthiazol-2-amine,4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N-o-tolylthiazol-2-amine, N-（2-fluorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine and N-（3-chloro-4-fluorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine have revealed high activity to A. fabae on the dosage500mg/L and dealwith72h.4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N-phenylthiazol-2-amineand N-（2-fluorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine have revealed50%of activity to Echinochloa crus-galli on the dosage2250g ai/ha tostem processing. N-（3-chloro-4-fluorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine has revealed weak activity to Echinochloa crus-galli. N-（2-fluorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine hasrevealed70%of activity to Digitaria sanguinalis on the dosage2250g ai/ha to soil treatment.4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N-phenylthiazol-2-amine has reveal-ed weak activity to Echinochloa crus-galli and Digitaria sanguinalis.The crystals of N-（4-chlorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine, N-（3,4-dimethylphenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine and4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N-（pyridin-2-yl）thiazol-2-amine suitable for X-ray structure determination were obtained, X-raydiffraction of the crystal shows that: the crystal of N-（4-chlorophenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine is a monoclinic system, C2/c of space group, unit cell dimensions: a=2.21140（12） nm, b=0.87602（5） nm, c=2.13911（12）nm, β=115.5380（10）°; V=3.7391（4） nm³, Z=8, Dc=1.375g/cm³, F（000）=1616, S=1.046, μ=0.333mm^-1, R1=0.0390, wR2=0.1079of Final R indices [I>2sigma（I）]; thecrystal of N-（3,4-dimethylphenyl）-4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）thiazol-2-amine is a monoclinic system, C2of chiral space group, unit cell dimensions: a=1.91303（14） nm, b=0.54146（4） nm, c=2.10988（16） nm; β=114.0430（10）°; V=1.9959（3）nm³, Z=4, Dc=1.266g/cm³, μ=0.181mm^-1, F（000）=808; the crystal of4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N-（pyridin-2-yl）thiazol-2-amine is a monoclinicsystem, C2of chiral space group, unit cell dimensions: a=1.81328（14） nm, b=0.55969（5）nm, c=1.92195（15） nm; β=115.5420（10）°; V=1.7599（2） nm³, Z=4, Dc=1.334g/cm³, μ=0.201mm^-1, F（000）=744.