呋喃酚的合成工艺与其芳氨基噻唑衍生物的合成、表征和生物活性
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摘要
呋喃酚是制造克百威、丙硫克百威、丁硫克百威和呋线威等氨基甲酸酯类农药的重要中间体，存在环合反应步骤收率低、废渣量大的缺点，且克百威等下游农药产品毒性高将逐渐被淘汰。本论文对上述问题进行了针对性的研究：呋喃酚环合反应高效催化剂的制备和筛选，以提高呋喃酚环合收率；高效利用呋喃酚环合反应中生成的副产物；将农药药效基呋喃酚与噻唑胺拼合在同一分子中，合成了系列呋喃酚醚芳氨基噻唑新化合物，以期发现高效、广谱、低毒的新型农药。主要研究结果如下：
采用羧酸异丙醇铝作为呋喃酚环合反应的新型催化剂，探讨了羧酸异丙醇铝中羧酸根的数目、种类和催化剂的用量对催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚的影响；探讨了催化反应的机理；筛选了二元羧酸异丙醇铝和二乙酸酚铝催化剂；选择了二乙酸异丙醇铝、丙二酸异丙醇铝和二乙酸呋喃酚铝催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚，其收率分别为80.8%、80.9%和80.8%。新型催化剂制备简单，应用价值高。
在呋喃酚环合反应中，分离纯化得到了：4-(2-甲基烯丙基)-1,2-苯二酚、4-(2-甲基丙烯基)-1,2-苯二酚、2,2-二甲基-4-(2-甲基-1-丙烯基)-2,3-二氢-7-苯并呋喃酚和2,2,7,7-四甲基-2,3,6,7-四氢苯并呋喃[7,6-b]呋喃等副产物；培养了2,2,7,7-四甲基-2,3,6,7-四氢苯并呋喃[7,6-b]呋喃单晶，通过X射线单晶衍射测定其属于单斜晶系，P21/n空间群，晶胞参数：a=0.87553(6) nm，b=0.60721(4) nm，c=2.32082(17) nm；β=92.1860(10)°；V=1.232.92(15) nm~3，Z=4，Dc=1.176g/cm~3，μ=0.077mm~(-1)，F(000)=472。
推测了催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚的反应机理：2,2,7,7-四甲基-2,3,6,7-四氢苯并呋喃[7,6-b]呋喃由1,2-二（2-甲基烯丙氧基）苯在催化剂作用下加热发生Claisen重排；2-(2-甲基烯丙氧基)苯酚经Claisen重排和环合连串反应生成呋喃酚，同时还可以发生连串的Cope重排反应，生成副产物4-(2-甲基烯丙基)-1,2-苯二酚。
4-(2-甲基烯丙基)-1,2-苯二酚副产物分子中含有活性官能团酚羟基和2-甲基烯丙基，可以经过结构改造合成高附加值的精细化学品：以4-(2-甲基烯丙基)-1,2-苯二酚为原料，经甲醚化、异构化、臭氧化得藜芦醛；经亚甲醚化、异构化、臭氧化得胡椒醛；4-(2-甲基烯丙基)-1,2-苯二酚经亚甲醚化、硼氢化-氧化、Corey-Kim氧化得到了附加值更高的新洋茉莉醛。
设计将农药药效基呋喃酚与噻唑拼合在同一分子；以呋喃酚为原料，合成了39种呋喃酚醚芳氨基噻唑类新化合物，总收率45.3~52.1%（以呋喃酚计）。结构经核磁、质谱和元素分析等确证。新化合物生物活性筛选结果显示：在有效成分浓度为500mg/L时，处理72h，4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-苯胺基噻唑、4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-甲基苯氨基）噻唑、4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-氟苯氨基）噻唑和4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2（-3-氯4-氟苯氨基）噻唑对蚕豆蚜有较高的活性；在2250g ai/ha浓度下进行茎叶处理，4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-苯胺基噻唑和4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-氟苯氨基）噻唑对稗的除草活性均为50%；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（3-氯4-氟苯氨基）噻唑对稗有一定的除草活性；在2250g ai/ha浓度下进行土壤处理，4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-氟苯氨基）噻唑对马唐的除草活性为70%；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-苯胺基噻唑对马唐和稗有一定的除草活性。
培养了4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（4-氯苯氨基）噻唑、4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（3,4-二甲基苯氨基）噻唑和4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-吡啶氨基）噻唑单晶，结构经X-射线衍射确定。4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（4-氯苯氨基）噻唑属于单斜晶系，空间群为C2/c，晶胞参数a=2.21140(12) nm，b=0.87602(5) nm，c=2.13911(12) nm，β=115.5380(10)°；V=3.7391(4) nm~3，Z=8，Dc=1.375g/cm~3，F(000)=1616，S=1.046，μ=0.333mm~(-1)，最终偏差因子R1=0.0390，wR2=0.1079；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（3,4-二甲基苯氨基）噻唑为单斜晶体，C2手性空间群，晶胞参数：a=1.91303(14) nm，b=0.54146(4) nm，c=2.10988(16) nm；β=114.0430(10)°；V=1.9959(3) nm~3，Z=4，Dc=1.266g/cm~3，μ=0.181mm~(-1)，F(000)=808；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-吡啶氨基）噻唑为单斜晶体，C2手性空间群，晶胞参数：a=1.81328(14) nm，b=0.55969(5) nm，c=1.92195(15) nm；β=115.5420(10)°；V=1.7599(2) nm~3，Z=4，Dc=1.334g/cm~3，μ=0.201mm~(-1)，F(000)=744。
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) nm~3, Z=4, Dc=1.176g/cm~3, 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 of45.3~52.1%(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) nm~3, Z=8, Dc=1.375g/cm~3, 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)nm~3, Z=4, Dc=1.266g/cm~3, 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) nm~3, Z=4, Dc=1.334g/cm~3, μ=0.201mm~(-1), F(000)=744.
采用羧酸异丙醇铝作为呋喃酚环合反应的新型催化剂，探讨了羧酸异丙醇铝中羧酸根的数目、种类和催化剂的用量对催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚的影响；探讨了催化反应的机理；筛选了二元羧酸异丙醇铝和二乙酸酚铝催化剂；选择了二乙酸异丙醇铝、丙二酸异丙醇铝和二乙酸呋喃酚铝催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚，其收率分别为80.8%、80.9%和80.8%。新型催化剂制备简单，应用价值高。
在呋喃酚环合反应中，分离纯化得到了：4-(2-甲基烯丙基)-1,2-苯二酚、4-(2-甲基丙烯基)-1,2-苯二酚、2,2-二甲基-4-(2-甲基-1-丙烯基)-2,3-二氢-7-苯并呋喃酚和2,2,7,7-四甲基-2,3,6,7-四氢苯并呋喃[7,6-b]呋喃等副产物；培养了2,2,7,7-四甲基-2,3,6,7-四氢苯并呋喃[7,6-b]呋喃单晶，通过X射线单晶衍射测定其属于单斜晶系，P21/n空间群，晶胞参数：a=0.87553(6) nm，b=0.60721(4) nm，c=2.32082(17) nm；β=92.1860(10)°；V=1.232.92(15) nm~3，Z=4，Dc=1.176g/cm~3，μ=0.077mm~(-1)，F(000)=472。
推测了催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚的反应机理：2,2,7,7-四甲基-2,3,6,7-四氢苯并呋喃[7,6-b]呋喃由1,2-二（2-甲基烯丙氧基）苯在催化剂作用下加热发生Claisen重排；2-(2-甲基烯丙氧基)苯酚经Claisen重排和环合连串反应生成呋喃酚，同时还可以发生连串的Cope重排反应，生成副产物4-(2-甲基烯丙基)-1,2-苯二酚。
4-(2-甲基烯丙基)-1,2-苯二酚副产物分子中含有活性官能团酚羟基和2-甲基烯丙基，可以经过结构改造合成高附加值的精细化学品：以4-(2-甲基烯丙基)-1,2-苯二酚为原料，经甲醚化、异构化、臭氧化得藜芦醛；经亚甲醚化、异构化、臭氧化得胡椒醛；4-(2-甲基烯丙基)-1,2-苯二酚经亚甲醚化、硼氢化-氧化、Corey-Kim氧化得到了附加值更高的新洋茉莉醛。
设计将农药药效基呋喃酚与噻唑拼合在同一分子；以呋喃酚为原料，合成了39种呋喃酚醚芳氨基噻唑类新化合物，总收率45.3~52.1%（以呋喃酚计）。结构经核磁、质谱和元素分析等确证。新化合物生物活性筛选结果显示：在有效成分浓度为500mg/L时，处理72h，4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-苯胺基噻唑、4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-甲基苯氨基）噻唑、4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-氟苯氨基）噻唑和4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2（-3-氯4-氟苯氨基）噻唑对蚕豆蚜有较高的活性；在2250g ai/ha浓度下进行茎叶处理，4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-苯胺基噻唑和4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-氟苯氨基）噻唑对稗的除草活性均为50%；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（3-氯4-氟苯氨基）噻唑对稗有一定的除草活性；在2250g ai/ha浓度下进行土壤处理，4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-氟苯氨基）噻唑对马唐的除草活性为70%；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-苯胺基噻唑对马唐和稗有一定的除草活性。
培养了4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（4-氯苯氨基）噻唑、4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（3,4-二甲基苯氨基）噻唑和4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-吡啶氨基）噻唑单晶，结构经X-射线衍射确定。4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（4-氯苯氨基）噻唑属于单斜晶系，空间群为C2/c，晶胞参数a=2.21140(12) nm，b=0.87602(5) nm，c=2.13911(12) nm，β=115.5380(10)°；V=3.7391(4) nm~3，Z=8，Dc=1.375g/cm~3，F(000)=1616，S=1.046，μ=0.333mm~(-1)，最终偏差因子R1=0.0390，wR2=0.1079；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（3,4-二甲基苯氨基）噻唑为单斜晶体，C2手性空间群，晶胞参数：a=1.91303(14) nm，b=0.54146(4) nm，c=2.10988(16) nm；β=114.0430(10)°；V=1.9959(3) nm~3，Z=4，Dc=1.266g/cm~3，μ=0.181mm~(-1)，F(000)=808；4-(7-甲氧基-2,2-二甲基-2,3-二氢-5-苯并呋喃基)-2-（2-吡啶氨基）噻唑为单斜晶体，C2手性空间群，晶胞参数：a=1.81328(14) nm，b=0.55969(5) nm，c=1.92195(15) nm；β=115.5420(10)°；V=1.7599(2) nm~3，Z=4，Dc=1.334g/cm~3，μ=0.201mm~(-1)，F(000)=744。
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) nm~3, Z=4, Dc=1.176g/cm~3, 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 of45.3~52.1%(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) nm~3, Z=8, Dc=1.375g/cm~3, 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)nm~3, Z=4, Dc=1.266g/cm~3, 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) nm~3, Z=4, Dc=1.334g/cm~3, μ=0.201mm~(-1), F(000)=744.
引文
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