CN117263862A - 一类苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮类化合物及其合成和用途 - Google Patents
一类苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮类化合物及其合成和用途 Download PDFInfo
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- CN117263862A CN117263862A CN202311207912.1A CN202311207912A CN117263862A CN 117263862 A CN117263862 A CN 117263862A CN 202311207912 A CN202311207912 A CN 202311207912A CN 117263862 A CN117263862 A CN 117263862A
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- -1 thioketone compound Chemical class 0.000 title claims abstract description 445
- OWVQIMUTZWMDGQ-UHFFFAOYSA-N 1,3-dihydroimidazole Chemical compound [CH]1NC=CN1 OWVQIMUTZWMDGQ-UHFFFAOYSA-N 0.000 title claims abstract description 7
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- AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 claims description 23
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- 238000000034 method Methods 0.000 claims description 4
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- MYXNWWDJRWCURH-UHFFFAOYSA-N ethoxymethanethioic s-acid Chemical compound CCOC(S)=O MYXNWWDJRWCURH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
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- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical compound SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 18
- CLEJZSNZYFJMKD-UHFFFAOYSA-N 3h-1,3-oxazole-2-thione Chemical compound SC1=NC=CO1 CLEJZSNZYFJMKD-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- XYVMOLOUBJBNBF-UHFFFAOYSA-N 3h-1,3-oxazol-2-one Chemical compound OC1=NC=CO1 XYVMOLOUBJBNBF-UHFFFAOYSA-N 0.000 description 16
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- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 11
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
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- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- SMOLOXXOYDWKRI-UHFFFAOYSA-N 1-(2-bromophenoxy)propan-2-one Chemical compound CC(=O)COC1=CC=CC=C1Br SMOLOXXOYDWKRI-UHFFFAOYSA-N 0.000 description 2
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- CRBJBYGJVIBWIY-UHFFFAOYSA-N 2-isopropylphenol Chemical compound CC(C)C1=CC=CC=C1O CRBJBYGJVIBWIY-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000220451 Canavalia Species 0.000 description 2
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- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
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- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
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- 239000002585 base Substances 0.000 description 1
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- ANCLJVISBRWUTR-UHFFFAOYSA-N diaminophosphinic acid Chemical compound NP(N)(O)=O ANCLJVISBRWUTR-UHFFFAOYSA-N 0.000 description 1
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 1
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- 125000005541 phosphonamide group Chemical group 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
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- 230000035484 reaction time Effects 0.000 description 1
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- 229940083618 sodium nitroprusside Drugs 0.000 description 1
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- 208000019206 urinary tract infection Diseases 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
- A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C05—FERTILISERS; MANUFACTURE THEREOF
- C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
- C05G3/00—Mixtures of one or more fertilisers with additives not having a specially fertilising activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/36—One oxygen atom
- C07D263/38—One oxygen atom attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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Abstract
本发明公开了一类苯酚‑1,3‑噁唑/二氢咪唑‑2‑酮/硫酮化合物，具有如下结构通式：
Description
技术领域
本发明涉及一类苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物及其制法，及其在制备治疗胃炎、胃溃疡、尿路结石、尿路炎症等药物和尿素类肥料、动物饲料添加剂中的应用。
技术背景
幽门螺旋杆菌(Helicobacter pylori，HP)是一种螺旋形的革兰阴性厌氧菌，能在人胃强酸性条件下生存，可引发一系列的疾病，包括胃肠道炎症、胃溃疡、胃癌、肾结石和肾盂肾炎等。
尿素酶(Urease)又名尿素酰胺水解酶，能快速催化水解尿素生成氨。HP通过产生尿素酶来水解体内的尿素释放氨，中和胃酸，使得HP能在胃酸环境下生存，因此，尿素酶是幽门螺旋杆菌的主要毒力因子。解脲支原体(Ureaplasma urealyticum)等感染尿道，导致尿液中尿素水解，引起尿液碱化，进而导致Ca2+、Mg2+等离子沉淀形成尿路结石等疾病。因此，目前治疗尿素酶相关疾病的重要策略之一是使用尿素酶抑制剂。尿素酶抑制剂对尿素酶活性的抑制作用显著，尿素酶的活性受到抑制后水解尿素的能力下降，达到降低胃内的氨浓度、破坏HP生存的微环境的目的，从而根除HP，或阻止尿液碱化，防止结石形成并促进原有结石溶解。目前，使用抗生素治疗这类疾病存在的主要问题是抗生素耐药问题，导致有效率显著下降甚至无效，特别是对于尿路结石，因抗生素难以达到结石内部，因而难以根治。
在农业中，因为土壤尿素酶活性，导致施用的尿素类氮肥迅速分解，造成氨的迅速释放，一方面导致巨大的经济损失，另一方面甚至造成烧苗，给农业生产造成损失。在畜牧业中，反刍动物，如奶牛，其瘤胃中的微生物能产生尿素酶，饲料中的尿素会被分解产生氨，而这些微生物可以利用氨合成蛋白质，可以被奶牛利用从而提高产奶量，因此在反刍动物的饲料中添加尿素可以提高经济效益，但若短时间内产生过多的氨，会被瘤胃吸收而引起中毒。近些年来，土壤尿素酶抑制剂被广泛应用在农业生产和在反刍动物中的应用研究中，在提高农业生产、带动国民经济中发挥着积极作用。
尿素酶抑制剂是通过靶向活性位点或模拟尿素酶的底物来设计的，目前已知的尿素酶抑制剂主要分为氧肟酸类、磷酰胺类、酚醌类、杂环类、尿素类似物类、席夫碱类、重金属类及其他天然产物类等。目前为止，乙酰氧肟酸是医用领域中唯一获得美国食品和药物管理局(FDA)批准上市尿素酶抑制剂，但因其治疗的剂量大(成人至少1000mg/d)从而导致出现一些不良反应，而高活性的磷酸二酰胺类尿素酶抑制剂在酸性环境中不稳定，阻碍了其在临床上的应用。因此，迫切需要开发一些具有高活性、低毒性的新型尿素酶抑制剂。
发明内容
本发明的目的在于设计并合成一类苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮(I)尿素酶抑制剂，在深入研究构效关系的基础上，发现了高活性的新型尿素酶抑制剂，并提供苯酚-1,3-噁唑-2(3H)-酮/硫酮类化合物的制法。
本发明的技术方案如下：
一类苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物，具有如下结构通式：
其中，n＝0-3的整数，X代表CH2或SCH2，Y＝O或S，Z代表O或NH，R1、R2、R3、R4和R5相同或不同，代表H、C1-C6的烷基(优选Me、Et、i-Pr或t-Bu)、卤素基团、OR、SR、NHR、N(R)2中的一种或几种，其中R为C1-C6的烷基(优选Me、Et、i-Pr或t-Bu)。
优选的，本发明所述的苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物，R1、R2、R3、R4和R5代表H，或者，R1、R2、R3、R4和R5其中任意一个或两个基团代表Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR或N(R)2，其中R为Me、Et或Bn，R1、R2、R3、R4和R5中的其余基团为H。
本发明的优选方案，选自下列各组之任一组：
R2＝R3＝R4＝R5＝H,R1＝H、Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R1＝R3＝R4＝R5＝H,R2＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R1＝R2＝R4＝R5＝H,R3＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R3＝R4＝R5＝H,R1＝R2＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R2＝R4＝R5＝H,R1＝R3＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R1＝R4＝R5＝H,R2＝R3＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R2＝R3＝R5＝H,R1＝R4＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R2＝R3＝R4＝H,R1＝R5＝Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR、N(R)2，其中R为Me、Et或Bn；
R2＝R4＝H,R1＝R3＝R5＝Me、Et、F、Cl、Br、I。
更优选的，本发明所述的苯酚-1,3-噁唑-2(3H)-酮/硫酮化合物，n＝1-3的整数，X代表SCH2，Y＝O或S。
本发明另一目的在于提供本发明所述苯酚-1,3-噁唑-2(3H)-酮/硫酮化合物的制备方法，包括下列步骤：
(1)2-R1-3-R2-4-R3-5-R4-6-R5取代苯酚在碱性条件下与ω-溴代羧酸乙酯发生O-烃基化反应得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)羧酸乙酯(Ⅱ)，其中X＝CH2，n＝0-3，
或者(1)’将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基溴在碱性条件下与巯基羧酸乙酯发生S-烃基化反应，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)羧酸乙酯(Ⅱ)，其中X＝SCH2，n＝1-3，
(2)将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-2-烷酮(Ⅱ)与N-溴代丁二酰亚胺发生羰基α-H的溴代反应，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(IⅤ)，
(3)ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(IⅤ)与氨基甲酸乙酯或O-乙基硫代氨基甲酸酯发生N-烃基化反应，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-乙氧甲酰氨基-2-烷酮(V)，继而在碱性条件下发生环化反应，得到5-[ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基]-1,3-噁唑-2(3H)-酮/硫酮(I，Z＝O，Y＝O或S)，
或者(3)’将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(Ⅳ)与尿素或硫脲发生环化反应，得到4-[ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基]-1,3-二氢咪唑-2-酮/硫酮(I，Z＝NH，其中Y＝O或S)，
上述各步所述R1、R2、R3、R4、R5的定义与通式I中所述的定义相同。
具体包括如下步骤：
步骤(1)(X＝CH2，n＝1-3时)：常温下，将2-R1-3-R2-4-R3-5-R4-6-R5取代苯酚溶解在氢氧化钠的水溶液(用量约每克7mL)中备用。在反应瓶中加入四丁基溴化铵、甲苯(用量约每克5mL)、ω-溴代-2-烷酮，升温至60～100℃，滴入已经制备好的2-R1-3-R2-4-R3-5-R4-6-R5取代苯酚钠溶液，物质量之比为：n2-R1-3-R2-4-R3-5-R4-6R5取代苯酚:n氢氧化钠:nω-溴代丙酮:n四丁基溴化铵＝1:(1～1.5):(1～2):(0.01～0.08)。控制反应温度为60～100℃，剧烈搅拌4～8h，停止反应。将反应液冷却至室温后加入约3～10倍量的水，用1～3倍于混合液用量的乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝35∶1～10：1，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-2-烷酮(Ⅱ)；
或者，步骤(1)’(X＝SCH2，n＝1-3时)：常温下，在反应瓶中依次加入ω-巯基-2-烷酮和质量分数为3％的氢氧化钾的甲醇溶液，搅拌均匀后，将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基溴(III)加入到反应瓶中，物质量之比为：nω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基溴:nω-巯基-2-烷酮＝1∶(1～4)，控制反应温度为40～80℃，搅拌2～4h，停止反应。将反应液冷却至室温后加入2～5倍量的水，用1～3倍于混合液用量的乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝50:1～10:1，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5-苯氧基)烷硫基-2-烷酮，即X＝SCH2时的II；
步骤(2)：将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-2-烷酮(Ⅱ)、乙腈(用量约每克5mL)、对甲苯磺酸，依次加入到圆底烧瓶中，在搅拌下缓慢加入N-溴代丁二酰亚胺，物质量之比为：nω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-2-烷酮:n对甲苯磺酸:nN-溴代丁二酰亚胺＝1:(0.1～0.3):(1～2)。控制反应温度为50～80℃，搅拌1～4h。反应结束后，加入乙醚稀释，然后依次用蒸馏水、饱和NaHCO3溶液、饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝40:1～10:1，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(IⅤ)；
步骤(3)：在圆底烧瓶中加入氨基甲酸乙酯(Y＝O)或O-乙基硫代氨基甲酸酯(Y＝S)，在搅拌下加入无水丙酮(用量约每克15mL)，待充分溶解后加入无水K2CO3和ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(IⅤ)，回流反应5～12h。物质量之比为：n氨基甲酸酯/O-乙基硫代氨基甲酸酯:nK2CO3:nω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮＝(1～2):(3～7):1。将反应液冷却至室温后加入2～5倍量的水，用1～3倍于混合液用量的乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝25:1～1:1，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-乙氧甲酰氨基-2-烷酮(V，Y＝O或S)；
常温下，反应瓶中加入溶于ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-乙氧甲酰氨基-2-烷酮(V)的二噁烷溶液(用量约每克15mL)，加入浓盐酸酸化，室温下搅拌0.5～3h，冰浴冷却下分批加入K2CO3固体，升温至60～110℃，继续反应1～4h。物质量之比为：nω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-乙氧甲酰氨基-2-烷酮:nK2CO3＝1:(6～10)。反应结束，减压蒸去大部分溶剂，冷却至室温，在搅拌下加入约2～3倍量的水，冰浴下用稀盐酸酸化至pH在5～7之间，用1～4倍于混合液用量的乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝20:1～1:1，得到5-[ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基]-1,3-噁唑-2(3H)-酮/硫酮(I，Z＝O，其中Y＝O或S)。
或者步骤(3)’：在搅拌下依次加入尿素(X＝O)或硫脲(X＝S)(Ⅴ)，5％的DMF(用量约每克15mL)水溶液，待充分溶解后加入K2CO3和ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(Ⅳ)，加热至40～80℃，反应5～12h。物质量之比为：nω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮:n尿素/硫脲:nK2CO3＝1:(1～2):(3～7)。将反应液冷却至室温后加入4～7倍量的水，用1～3倍于混合液用量的乙酸乙酯萃取，共3次，合并有机层，水洗，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝5:1～1:1，得到4-[ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基]-1,3-二氢咪唑-2-酮/硫酮(I，Z＝NH，Y＝O或S)。
上述各步所述R1、R2、R3、R4、R5的定义与通式I中所述的定义相同。
本发明另一目的在于提供本发明所述苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物在制备尿素酶抑制剂中的应用。所述尿素酶抑制剂为治疗胃肠道炎症、胃溃疡、胃癌、肾结石或肾盂肾炎的药物或者用于尿素类肥料或动物饲料添加剂。
本发明优点：
基于现代药物设计的原理，通过发现尿素酶活性口袋上的特异性结合区域，采用定向设计的思想，在分子特定的空间方向配置特定的基团，从而使其与活性口袋的特定区域产生特异性结合，基于这样的认识和基础，本发明设计并合成了具有Ⅰ所示结构的新型尿素酶抑制剂。试验表明，多数化合物对尿素酶表现出了优良的抑制活性。
具体实施方式
通过以下实施例进一步详细说明本发明，但应注意本发明的范围并不受这些实施例的任何限制。
实施例1：5-[(2-异丙基苯氧基)甲基]噁唑-2(3H)-硫酮(15)的制备
常温下，将2-异丙基苯酚2.04g(15mmol)溶解在5.04mL氢氧化钠溶液中(含氢氧化钠0.72g，18mmol)备用。在反应瓶中加入0.1g四丁基溴化铵、4mL甲苯、2.45g(18mmol)1-溴丙酮，升温至100℃，滴入已经制备好的2-异丙基苯酚钠溶液，控制反应温度为100℃，剧烈搅拌5h，停止反应。将反应液冷却至室温后加入60mL水，用75mL乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯、甲苯和过量的1-溴丙酮，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝25:1，得到1-(2-异丙基苯氧基)丙酮2.29g，产率为79.5％；
将1-(2-异丙基苯氧基)丙酮2.29g(12mmol)、11.45mL乙腈、0.41g(2.4mmol)对甲苯磺酸，依次加入到圆底烧瓶中，在搅拌下缓慢加入2.14g(12mmol)N-溴代丁二酰亚胺，在60℃下反应2h。反应结束后，加入乙醚稀释，然后依次用蒸馏水、饱和NaHCO3溶液、饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝20:1，得到3-(2-异丙基苯氧基)-1-溴丙酮2.31g，产率为71.3％；
在圆底烧瓶中加入0.84g(8mmol)O-乙基硫代氨基甲酸酯，在搅拌下加入12.6mL无水丙酮，待充分溶解后加入3.3g(24mmol)无水K2CO3和2.16g(8mmol)3-(2-异丙基苯氧基)-1-溴丙酮，回流反应5h。反应结束后，将反应液冷却至室温后加入30mL水，用60mL乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝15:1，得到3-(2-异丙基苯氧基)-1-乙氧硫代甲酰氨基-2-酮1.97g，产率为83.5％；
常温下，反应瓶中加入26.55mL溶于1.77g(6mmol)3-(2-异丙基苯氧基)-1-乙氧硫代甲酰氨基-2-酮的二噁烷溶液，加入0.6mL浓盐酸酸化，室温下搅拌0.5h，冰浴冷却下分3批加入4.97g(36mmol)K2CO3固体，升温至70℃，继续反应2h。将反应液冷却至室温后加入30mL水，冰浴下用稀盐酸酸化至pH在5～7之间，用60mL乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝9:1，得到5-[(2-异丙基苯氧基)甲基]噁唑-2(3H)-硫酮(15)1.23g，产率为82.3％，Mp 145～147℃；ESIMS m/z：250[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.34(s,1H),7.36–7.29(dd,1H),7.17–7.06(td,1H),7.00(dt,1H),6.99(dd,1H),4.63(s,2H),3.33(m,1H),1.27(d,6H).
实施例2：
按实施例1相似的方法，用不同的取代形式的苯酚为原料，合成了表1所列的苯酚-1,3-噁唑-2(3H)-酮/硫酮系列化合物1～117。
表1通式I中苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮系列化合物的各R基团
注：初始原料均购自于国药集团。
实施例3：4-[(2-溴苯氧基)甲基]1,3-二氢咪唑-2-酮(120)的制备
常温下，将2-溴苯酚2.58g(15mmol)溶解在5.04mL氢氧化钠溶液中(含氢氧化钠0.72g，18mmol)备用。在反应瓶中加入0.1g四丁基溴化铵、4mL甲苯、2.45g(18mmol)1-溴丙酮，升温至100℃，滴入已经制备好的2-溴苯酚钠溶液，控制反应温度为100℃，剧烈搅拌4h，停止反应。将反应液冷却至室温后加入60mL水，用75mL乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯、甲苯和过量的1-溴丙酮，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝30：1，得到1-(2-溴苯氧基)丙酮2.47g，产率为72.2％；
将1-(2-溴苯氧基)丙酮2.28g(10mmol)、11.4mL乙腈、0.34g(2mmol)对甲苯磺酸，依次加入到圆底烧瓶中，在搅拌下缓慢加入1.78g(10mmol)N-溴代丁二酰亚胺，在60℃下反应3h。反应结束后，加入乙醚稀释，然后依次用蒸馏水、饱和NaHCO3溶液、饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚：乙酸乙酯＝22∶1，得到3-(2-溴苯氧基)-1-溴丙酮2.35g，产率为76.3％；
在搅拌下依次加入0.36g(6mmol)尿素，5.4mL5％的DMF水溶液，待充分溶解后加入2.48g(18mmol)K2CO3和1.85g(6mmol)3-(2-溴苯氧基)-1-溴丙酮，加热至50℃，反应7h。将反应液冷却至室温后加入30mL水，用60mL乙酸乙酯萃取，共3次，合并有机层，无水硫酸镁干燥、过滤、减压除去乙酸乙酯，硅胶柱层析纯化，洗脱剂体积比：石油醚:乙酸乙酯＝14:1，得到4-[(2-溴苯氧基)甲基]1,3-二氢咪唑-2-酮(120)1.34g，产率为83.3％，Mp144～146℃；ESIMS m/z：269[M+H]+；1HNMR(400MHz,CDCl3)δ8.79(s,1H),8.53(s,1H),7.52(dd,1H),7.25(td,1H),6.90(dd,1H),6.84(td,1H),6.17(s,1H),5.03(s,2H).
实施例4：
按实施例3相似的方法，用不同的取代形式的苯酚为原料，合成了表1所列的苯酚-1,3-二氢咪唑-2-酮/硫酮系列化合物118～237。
表2通式I中苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮系列化合物的各R基团
注：初始原料均购自于国药集团
实施例5：化合物的抑酶活性
所有的试验都在pH为8.2的溶液中进行(0.01M的K2HPO4，1mM的EDTA，0.01M的LiCl)。往96孔板中加入25μL Jack bean(刀豆)尿素酶(10U/mL)和25μL某浓度被测化合物的溶液，每个浓度设置至少3个平行孔，在37℃下培育2h，然后加入含有20mM尿素的磷酸缓冲液55μL，在30℃下培育15min，加入50μL酚试剂(含苯酚1％与含硝普钠0.005％的混合溶液)和50μL碱试剂(含NaOH 0.5％与0.1％活性氯的NaOCl的混合溶液)，在室温下放置50min后，用酶标仪测定630nm下的OD值，百分抑制率按下式计算：
按上述方法测定一系列浓度的被测物质的抑制率，根据抑制率-浓度曲线计算出半抑制率IC50，至少独立进行3次试验，求IC50平均值。IC50越小，表明此化合物的活性越高，结果见表3和表4。
结果表明：本发明所述的部分苯酚-1,3,4-噁二唑-2(3H)-酮/硫酮系列化合物对尿素酶有较好的抑制活性，X为SCH2的化合物均比阳性对照乙酰氧肟酸(AHA)的活性更高。
表3苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮系列化合物对刀豆尿素酶的抑制作用(IC50)
结果表明，X为SCH2的化合物对刀豆尿素酶有显著的抑制作用，是市场药物乙酰氧肟酸的13～6059倍。
表4苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮系列化合物对刀豆尿素酶的抑制作用(IC50)
结果表明，X为SCH2的化合物对刀豆尿素酶有显著的抑制作用，是市场药物乙酰氧肟酸的14～8408倍。
本发明的上述实施例表明：本发明找到化合物与尿素酶作用的关键区域，形成了特异性结合，显著提高了抑制尿素酶的活性。
化合物1～237的熔点、质谱及氢谱数据：
5-(苯氧甲基)噁唑-2(3H)-酮 (1)
Mp 106～108℃；ESIMS m/z：192[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.18(dt,2H),6.96–6.83(m,2H),6.82(tt,1H),5.85(s,1H),4.78–4.48(s,2H).
5-(邻甲苯氧基甲基)噁唑-2(3H)-酮 (2)
Mp 113～115℃；ESIMS m/z：206[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.03(dd,1H),7.00(td,1H),6.85(td,1H),6.73(dd,1H),5.82(s,1H),4.62(s,2H),2.21(s,3H).
5-[(2-异丙基苯氧基)甲基]噁唑-2(3H)-酮 (3)
Mp 127～129℃；ESIMS m/z：234[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.27(dd,1H),7.06(td,1H),7.00(td,1H),6.85(dd,1H),5.72(s,1H),4.61(s,2H),3.13(m,1H),1.22(d,6H).
5-[(3-氟苯氧基)甲基]噁唑-2(3H)-酮 (4)
Mp 115～117℃；ESIMS m/z：210[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.27(td,1H),6.78(ddt,1H),6.73(dt,1H),6.58(dt,1H),5.76(s,1H),4.69–4.45(s,2H).
5-[(3-苯氧基苯氧基)甲基]噁唑-2(3H)-酮 (5)
Mp 152～154℃；ESIMS m/z：284[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(dt,2H),7.28(s,1H),7.26(dd,2H),7.13(tt,1H),7.05–6.94(m,2H),6.68(dt,1H),6.52(dt,1H),5.75(s,1H),4.72–4.54(s,2H).
5-[(4-乙基苯氧基)甲基]噁唑-2(3H)-酮 (6)
Mp 120～122℃；ESIMS m/z：220[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(s,1H),7.14–7.06(m,2H),6.83–6.72(m,2H),5.77(s,1H),4.63(s,2H),2.84–2.50(m,2H),1.17(t,3H).
5-[(4-异丁基苯氧基)甲基]噁唑-2(3H)-酮 (7)
Mp 134～136℃；ESIMS m/z：248[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(s,1H),7.08(dd,2H),6.87–6.77(m,2H),5.77(s,1H),4.63(s,2H),2.62–2.33(d,2H),1.88(m,1H),0.87(d,6H).
5-[(2,3-二氯苯氧基)甲基]噁唑-2(3H)-酮 (8)
Mp 140～142℃；ESIMS m/z：260[M+H]+；1HNMR(400MHz,CDCl3)δ7.41(dd,1H),7.32(s,1H),7.18(t,1H),6.98(dd,1H),5.84(s,1H),4.62(s,2H).
5-[(2,3-二溴苯氧基)甲基]噁唑-2(3H)-酮 (9)
Mp 185～187℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.24(dd,1H),7.09(t,1H),6.86(dd,1H),5.86(s,1H),4.63(s,2H).
5-[(2,4-二甲基苯氧基)甲基]噁唑-2(3H)-酮 (10)
Mp 120～122℃；ESIMS m/z：220[M+H]+；1HNMR(400MHz,CDCl3)δ7.31(s,1H),7.02–6.94(d,1H),6.87(dd,1H),6.66(d,1H),5.82(s,1H),4.73–4.45(s,2H),2.35(s,3H),2.24–2.14(s,3H).
5-[(2,4-二异丙基苯氧基)甲基]噁唑-2(3H)-酮 (11)
Mp 148～150℃；ESIMS m/z：276[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.15–7.08(d,1H),7.03(dd,1H),6.82(d,1H),5.74(s,1H),4.62(s,2H),3.25–3.12(m,1H),2.95–2.82(m,1H),1.25(d,12H).
5-[(3,4-二苄氧基苯氧基)甲基]噁唑-2(3H)-酮 (12)
Mp 212～214℃；ESIMS m/z：404[M+H]+；1HNMR(400MHz,CDCl3)δ7.48–7.20(m,10H),7.35(s,1H),7.05(d,1H),6.84(d,1H),6.65(dd,1H),5.78(s,1H),5.13(s,4H),4.64(s,2H).
5-[(2,5-二异丙基苯氧基)甲基]噁唑-2(3H)-酮 (13)
Mp 148～150℃；ESIMS m/z：276[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.18(d,1H),7.03(dd,1H),6.99(d,1H),5.80(s,1H),4.72–4.48(s,2H),3.24(m,1H),3.05–2.87(m,1H),1.26(dd,12H).
5-(苯氧甲基)噁唑-2(3H)-硫酮 (14)
Mp 131～133℃；ESIMS m/z：222[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.36(s,1H),7.06–6.94(m,2H),6.89(td,1H),6.77(dd,1H),4.78–4.42(s,2H),2.26(s,3H).
5-[(2-异丙基苯氧基)甲基]噁唑-2(3H)-硫酮 (15)
Mp 145～147℃；ESIMS m/z：250[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.34(s,1H),7.36–7.29(dd,1H),7.17–7.06(td,1H),7.00(dt,1H),6.99(dd,1H),4.63(s,2H),3.33(m,1H),1.27(d,6H).
5-[(3-氟苯氧基)甲基]噁唑-2(3H)-硫酮 (16)
Mp 133～135℃；ESIMS m/z：226[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.28(dt,1H),7.25(s,1H),6.79(dt,1H),6.75(dt,1H),6.66(dt,1H),4.72–4.51(s,2H).
5-[(3-苯氧基苯氧基)甲基]噁唑-2(3H)-硫酮 (17)
Mp 170～172℃；ESIMS m/z：300[M+H]+；1HNMR(400MHz,CDCl3)δ11.28(s,1H),7.33(m,3H),7.22(s,1H),7.11(tt,1H),7.05–6.96(m,2H),6.74(dt,1H),6.52(m,2H),4.76–4.48(s,2H).
5-[(4-乙基苯氧基)甲基]噁唑-2(3H)-硫酮 (18)
Mp 138～140℃；ESIMS m/z：236[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.31(s,1H),7.13(dd,2H),6.92–6.82(dd,2H),4.60(s,2H),2.85–2.56(m,2H),1.17(t,3H).
5-[(4-异丁基苯氧基)甲基]噁唑-2(3H)-硫酮 (19)
Mp 152～154℃；ESIMS m/z：264[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.27(s,1H),7.08(dt,2H),6.87–6.78(m,2H),4.63(s,2H),2.56–2.30(m,2H),1.85(m,1H),0.89(d,6H).
5-[(2,3-二氯苯氧基)甲基]噁唑-2(3H)-硫酮 (20)
Mp 158～160℃；ESIMS m/z：276[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.49(s,1H),7.25(dd,1H),7.18(t,1H),6.87(dd,1H),4.63(s,2H).
5-[(2,3-二溴苯氧基)甲基]噁唑-2(3H)-硫酮 (21)
Mp 203～205℃；ESIMS m/z：366[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.52(s,1H),7.18(dd,1H),7.07(t,1H),6.92(dd,1H),4.63(s,2H).
5-[(2,4-二甲基苯氧基)甲基]噁唑-2(3H)-硫酮 (22)
Mp 138～140℃；ESIMS m/z：236[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.37(s,1H),6.98(d,1H),6.93(dd,1H),6.75(d,1H),4.72–4.51(s,2H),2.34(s,3H),2.25(s,3H).
5-[(2,4-二异丙基苯氧基)甲基]噁唑-2(3H)-硫酮 (23)
Mp 166～168℃；ESIMS m/z：292[M+H]+；1HNMR(400MHz,CDCl3)δ11.34(s,1H),7.39(s,1H),7.13(dd,1H),7.07–7.00(dd,1H),6.92(d,1H),4.63(s,2H),3.21(m,1H),2.94–2.81(m,1H),1.28(d,6H),1.23(d,6H).
5-[(3,4-二苄氧基苯氧基)甲基]噁唑-2(3H)-硫酮 (24)
Mp 230～232℃；ESIMS m/z：420[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.46–7.21(m,10H),7.27(s,1H),7.15(d,1H),6.92(d,1H),6.77(dd,1H),5.13(s,4H),4.62(s,2H).
5-[(2,5-二异丙基苯氧基)甲基]噁唑-2(3H)-硫酮 (25)
Mp 161～163℃；ESIMS m/z：292[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.39(s,1H),7.23–7.16(d,1H),7.06(d,1H),7.04(dd,1H),4.63(s,2H),3.34(m,1H),3.12–2.82(m,1H),1.24(t,12H).
5-[(2,6-二氟苯氧基)甲基]噁唑-2(3H)-硫酮 (26)
Mp 142～144℃；ESIMS m/z：244[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.43(s,1H),7.07(tt,1H),6.83(t,2H),4.62(s,2H).
5-[(2,6-二溴苯氧基)甲基]噁唑-2(3H)-硫酮 (27)
Mp 203～205℃；ESIMS m/z：366[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.51(d,2H),7.44(s,1H),6.86(t,1H),4.62(s,2H).
5-(苯氧甲硫基)噁唑-2(3H)-酮 (28)
Mp 122～124℃；ESIMS m/z：224[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(s,1H),7.30(dt,2H),6.90(m,3H),5.57(s,1H),5.52(s,2H).
5-[(2-乙基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (29)
Mp 136～138℃；ESIMS m/z：252[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.24(dd,1H),7.14(td,1H),6.98(td,1H),6.79(dd,1H),5.55(s,1H),5.53(s,2H),2.57(q,2H),1.18(t,3H).
5-[(2-碘苯氧甲硫基)甲基]噁唑-2(3H)-酮 (30)
Mp 185～187℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ7.72(dd,1H),7.35(s,1H),7.28(td,1H),6.95(dd,1H),6.82(td,1H),5.63(s,1H),5.51(s,2H).
5-[(间甲苯氧甲硫基)甲基]噁唑-2(3H)-酮 (31)
Mp 129～131℃；ESIMS m/z：238[M+H]+；1HNMR(400MHz,CDCl3)δ7.34(s,1H),7.23(t,1H),6.78(dt,1H),6.77(t,1H),6.74(dt,1H),5.55(s,1H),5.54(s,2H),2.31(s,3H).
5-[(3-异丙基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (32)
Mp 143～145℃；ESIMS m/z：266[M+H]+；1HNMR(400MHz,CDCl3)δ7.34(s,1H),7.23(t,1H),6.99(dt,1H),6.87(t,1H),6.73(dt,1H),5.55(s,1H),5.51(s,2H),3.07–2.86(m,1H),1.25(d,6H).
5-[(4-氟苯氧甲硫基)甲基]噁唑-2(3H)-酮 (33)
Mp 131～133℃；ESIMS m/z：242[M+H]+；1HNMR(400MHz,CDCl3)δ7.34(s,1H),7.11–6.99(m,2H),6.93–6.78(m,2H),5.55(s,1H),5.51(s,2H).
5-[(4-碘苯氧甲硫基)甲基]噁唑-2(3H)-酮 (34)
Mp 185～187℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ7.73–7.63(dd,2H),7.34(s,1H),6.69–6.56(dd,2H),5.54(s,1H),5.51(s,2H).
5-[(2,3-二甲基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (35)
Mp 136～138℃；ESIMS m/z：252[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(s,1H),7.08(t,1H),6.71(dd,1H),6.69(dd,1H),5.57(s,1H),5.53(s,2H),2.18(s,6H).
5-[(2,3-二叔丁基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (36)
Mp 178～180℃；ESIMS m/z：336[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.08(t,1H),6.98(dd,1H),6.68(dd,1H),5.56(s,1H),5.52(s,2H),1.33(s,9H),1.31(s,9H).
5-[(2,4-二乙基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (37)
Mp 150～152℃；ESIMS m/z：280[M+H]+；1HNMR(400MHz,CDCl3)δ7.34(s,1H),7.02(dd,1H),6.97(d,1H),6.72(d,1H),5.55(s,1H),5.50(s,2H),2.57(m,2H),2.37–2.24(m,2H),1.25(t,3H),1.18(t,3H).
5-[(2,4-二苄基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (38)
Mp 244～246℃；ESIMS m/z：468[M+H]+；1HNMR(400MHz,CDCl3)δ7.37(s,1H),7.36(d,1H),7.20(t,2H),7.19(dd,1H),7.28–7.13(dt,8H),6.94(d,1H),5.58(s,1H),5.53(s,2H),4.35(s,4H).
5-[(3,4-二氯苯氧甲硫基)甲基]噁唑-2(3H)-酮 (39)
Mp 156～158℃；ESIMS m/z：292[M+H]+；1HNMR(400MHz,CDCl3)δ7.31(s,1H),7.28(d,1H),6.96(d,1H),6.67(dd,1H),5.58(s,1H),5.51(s,2H).
5-[(3,4-二溴苯氧甲硫基)甲基]噁唑-2(3H)-酮 (40)
Mp 201～203℃；ESIMS m/z：382[M+H]+；1HNMR(400MHz,CDCl3)δ7.42(d,1H),7.35(s,1H),7.01(d,1H),6.72(dd,1H),5.55(s,1H),5.50(s,2H).
5-[(2,5-二氟苯氧甲硫基)甲基]噁唑-2(3H)-酮 (41)
Mp 140～142℃；ESIMS m/z：260[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.03(m,1H),6.75(m,1H),6.72(m,1H),5.55(s,1H),5.51(s,2H).
5-[(2,6-二甲基苯氧甲硫基)甲基]噁唑-2(3H)-酮 (42)
Mp 136～138℃；ESIMS m/z：252[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.06(t,1H),6.74(dd,2H),5.57(s,1H),5.50(s,2H),2.25(s,6H).
5-(苯氧甲硫基)噁唑-2(3H)-硫酮 (43)
Mp 140～142℃；ESIMS m/z：240[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.30(dt,2H),7.27(s,1H),6.93(dt,2H),6.91(tt,1H),5.52(s,2H).
5-[(2-乙基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (44)
Mp 154～156℃；ESIMS m/z：268[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.29(s,1H),7.25(dd,1H),7.13(dt,1H),7.10(dt,1H),7.05(dd,1H),5.53(s,2H),2.57(m,2H),1.17(t,3H).
5-[(2-碘苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (45)
Mp 203～205℃；ESIMS m/z：366[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.66(dd,1H),7.35(s,1H),7.29(td,1H),6.92(dd,1H),6.75(td,1H),5.53(s,2H).
5-[(3-甲基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (46)
Mp 147～149℃；ESIMS m/z：254[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.27(s,1H),7.23(t,1H),6.80(t,1H),6.79(dt,1H),6.78(dt,1H),5.52(s,2H),2.32(s,3H).
5-[(3-异丙基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (47)
Mp 161～163℃；ESIMS m/z：282[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.27(s,1H),7.24(t,1H),7.00(dq,1H),6.93–6.88(d,1H),6.82(dt,1H),5.52(s,2H),3.11–2.82(m,1H),1.24(d,6H).
5-[(4-氟苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (48)
Mp 149～151℃；ESIMS m/z：258[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.24(s,1H),7.12–7.02(m,2H),6.86(m,2H),5.53(s,2H).
5-[(4-碘苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (49)
Mp 203～205℃；ESIMS m/z：366[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.73–7.62(dd,2H),7.27(s,1H),6.72–6.63(dd,2H),5.51(s,2H).
5-[(2,3-二甲基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (50)
Mp 154～156℃；ESIMS m/z：268[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.29(s,1H),7.10(t,1H),6.73(dd,1H),6.71(dd,1H),5.52(s,2H),2.17(s,3H),2.15(s,3H).
5-[(2,3-二叔丁基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (51)
Mp 196～198℃；ESIMS m/z：352[M+H]+；1HNMR(400MHz,CDCl3)δ11.30(s,1H),7.26(s,1H),7.12(t,1H),7.04(dd,1H),6.83(dd,1H),5.52(s,2H),1.37(s,9H),1.35(s,9H).
5-[(2,4-二乙基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (52)
Mp 168～170℃；ESIMS m/z：296[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.25(s,1H),7.09–7.01(dd,1H),6.97(d,1H),6.81(d,1H),5.52(s,2H),2.59(m,2H),2.34–2.23(m,2H),1.27(t,3H),1.21(t,3H).
5-[(2,4-二苄硫基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (53)
Mp 262～264℃；ESIMS m/z：484[M+H]+；1HNMR(400MHz,CDCl3)δ11.30(s,1H),7.40(dd,1H),7.36–7.28(dt,8H),7.28(s,1H),7.27(d,1H),7.20(t,2H),7.02(d,1H),5.53(s,2H),4.35(s,4H).
5-[(3,4-二氯苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (54)
Mp 174～176℃；ESIMS m/z：308[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.32(d,1H),7.25(s,1H),6.96(d,1H),6.74(dd,1H),5.53(s,2H).
5-[(3,4-二溴苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (55)
Mp 219～221℃；ESIMS m/z：398[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.43(d,1H),7.24(s,1H),7.07(d,1H),6.75(dd,1H),5.53(s,2H).
5-[(2,5-二氟苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (56)
Mp 158～160℃；ESIMS m/z：276[M+H]+；1HNMR(400MHz,CDCl3)δ11.34(s,1H),7.28(s,1H),7.03(m,1H),6.87–6.71(m,2H),5.53(s,2H).
5-[(2,6-二甲基苯氧甲硫基)甲基]噁唑-2(3H)-硫酮 (57)
Mp 154～156℃；ESIMS m/z：268[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.30(s,1H),7.07(t,1H),7.05(dd,2H),5.53(s,2H),2.31(s,6H).
5-(苯氧乙硫基甲基)噁唑-2(3H)-酮 (58)
Mp 136～138℃；ESIMS m/z：252[M+H]+；1HNMR(400MHz,CDCl3)δ7.39–7.22(dt,2H),7.26(s,1H),6.93(m,3H),5.57(s,1H),4.32(t,2H),3.13(s,2H),2.84(t,2H).
5-[(2-叔丁基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (59)
Mp 164～166℃；ESIMS m/z：308[M+H]+；1HNMR(400MHz,CDCl3)δ7.26(s,1H),7.23(dd,1H),7.04(td,1H),6.92(td,1H),6.74(dd,1H),5.55(s,1H),4.32(t,2H),3.13(s,2H),2.85(t,2H),1.33(s,9H).
5-[(2-甲胺基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (60)
Mp 150～152℃；ESIMS m/z：281[M+H]+；1HNMR(400MHz,CDCl3)δ7.35(s,1H),6.84(t,2H),6.72(td,1H),6.63(dd,1H),5.61(s,1H),5.59(s,1H),4.30(t,2H),3.13(s,2H),2.84(t,2H),2.76(s,3H).
5-[(3-乙基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (61)
Mp 150～152℃；ESIMS m/z：280[M+H]+；1HNMR(400MHz,CDCl3)δ7.25(t,1H),7.13(s,1H),7.12–7.04(m,1H),6.81(dd,2H),5.55(s,1H),4.32(t,2H),3.10(s,2H),2.84(t,2H),2.57(q,2H),1.23(t,3H).
5-[(3-溴苯氧乙硫基)甲基]噁唑-2(3H)-酮 (62)
Mp 176～178℃；ESIMS m/z：332[M+H]+；1HNMR(400MHz,CDCl3)δ7.38(s,1H),7.37(dt,1H),7.16(t,1H),7.09(t,1H),6.87(dt,1H),5.75(s,1H),4.33(t,2H),3.12(s,2H),2.84(t,2H).
5-[(4-异丙基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (63)
Mp 157～159℃；ESIMS m/z：294[M+H]+；1HNMR(400MHz,CDCl3)δ7.36–7.28(m,2H),7.06(s,1H),6.93–6.85(m,2H),5.24(s,1H),4.33(t,2H),3.10(s,2H),2.97–2.89(m,1H),2.84(t,2H),1.23(d,6H)
5-[(4-氯苯氧乙硫基)甲基]噁唑-2(3H)-酮 (64)
Mp 153～155℃；ESIMS m/z：286[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(s,1H),7.32–7.29(dd,2H),7.07–6.95(td,2H),5.61(s,1H),4.32(t,2H),3.13(s,2H),2.84(t,2H).
5-[(2,3-二氟苯氧乙硫基)甲基]噁唑-2(3H)-酮 (65)
Mp 154～156℃；ESIMS m/z：288[M+H]+；1HNMR(400MHz,CDCl3)δ7.32(s,1H),7.05(td,1H),6.74(m,2H),5.55(s,1H),4.33(t,2H),3.12(s,2H),2.84(t,2H).
5-[(2,3-二碘苯氧乙硫基)甲基]噁唑-2(3H)-酮 (66)
Mp 262～264℃；ESIMS m/z：504[M+H]+；1HNMR(400MHz,CDCl3)δ7.29(s,1H),7.28(dd,1H),6.95(t,1H),6.77(dd,1H),5.58(s,1H),4.32(t,2H),3.10(s,2H),2.85(t,2H).
5-[(2,4-二异丁基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (67)
Mp 192～194℃；ESIMS m/z：364[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),7.03(dd,1H),6.96(d,1H),6.75(d,1H),5.55(s,1H),4.33(t,2H),3.13(s,2H),2.87(t,2H),2.45(t,4H),2.04(m,2H),0.88(dd,12H).
5-[(2,4-二溴苯氧乙硫基)甲基]噁唑-2(3H)-酮 (68)
Mp 215～217℃；ESIMS m/z：410[M+H]+；1HNMR(400MHz,CDCl3)δ7.75(d,1H),7.42(dd,1H),7.33(s,1H),6.84(d,1H),5.56(s,1H),4.32(t,2H),3.13(s,2H),2.85(t,2H).
5-[(3,4-二甲基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (69)
Mp 150～152℃；ESIMS m/z：280[M+H]+；1HNMR(400MHz,CDCl3)δ7.27(s,1H),6.98(d,1H),6.67(d,1H),6.63(dd,1H),5.62(s,1H),4.33(t,2H),3.12(s,2H),2.85(t,2H),2.24(s,3H),2.23(s,3H).
5-[(3,4-二异丙基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (70)
Mp 178～180℃；ESIMS m/z：336[M+H]+；1HNMR(400MHz,CDCl3)δ7.29(s,1H),7.15(d,1H),6.77(d,1H),6.72(dd,1H),5.55(s,1H),4.33(t,2H),3.47(m,1H),3.11(s,2H),3.08(m,1H),2.85(t,2H),1.32(dd,12H).
5-[(2,5-二叔丁基苯氧乙硫基)甲基]噁唑-2(3H)-酮 (71)
Mp 192～194℃；ESIMS m/z：364[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),7.18(d,1H),6.86(dd,1H),6.84(d,1H),5.55(s,1H),4.32(t,2H),3.13(s,2H),2.87(t,2H),1.34(s,9H),1.29(s,9H).
5-[(2,5-二氯苯氧乙硫基)甲基]噁唑-2(3H)-酮 (72)
Mp 170～172℃；ESIMS m/z：320[M+H]+；1HNMR(400MHz,CDCl3)δ7.31(s,1H),7.28(s,1H),7.06(dd,1H),6.98(d,1H),5.57(s,1H),4.33(t,2H),3.12(s,2H),2.85(t,2H).
5-(苯氧乙硫基甲基)噁唑-2(3H)-硫酮 (73)
Mp 154～156℃；ESIMS m/z：268[M+H]+；1HNMR(400MHz,CDCl3)δ11.31(s,1H),7.35–7.23(m,2H),7.12(s,1H),6.93(m,3H),4.32(t,2H),3.12(s,2H),2.84(t,2H).
5-[(2-叔丁基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (74)
Mp 182～184℃；ESIMS m/z：324[M+H]+；1HNMR(400MHz,CDCl3)δ10.85(s,1H),7.24(dd,1H),7.07(s,1H),7.04(td,1H),6.88(td,1H),6.52(dd,1H),4.32(t,2H),3.13(s,2H),2.85(t,2H),1.38(s,9H).
5-[(2-甲氨基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (75)
Mp 168～170℃；ESIMS m/z：297[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.25(s,1H),6.86(td,1H),6.72–6.56(m,3H),5.72(s,1H),4.32(t,2H),3.14(s,2H),2.84(t,2H),2.73(s,3H).
5-[(3-乙基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (76)
Mp 168～170℃；ESIMS m/z：296[M+H]+；1HNMR(400MHz,CDCl3)δ11.26(s,1H),7.24(t,1H),7.18(s,1H),7.08–7.00(dd,1H),6.81(m,2H),4.33(t,2H),3.12(s,2H),2.87(t,2H),2.66–2.52(q,2H),1.24(t,3H).
5-[(3-溴苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (77)
Mp 194～196℃；ESIMS m/z：348[M+H]+；1HNMR(400MHz,CDCl3)δ11.36(s,1H),7.38(dt,1H),7.34(s,1H),7.22–7.13(m,2H),6.88(dt,1H),4.32(t,2H),3.13(s,2H),2.84(t,2H).
5-[(4-异丙基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (78)
Mp 175～177℃；ESIMS m/z：310[M+H]+；1HNMR(400MHz,CDCl3)δ10.93(s,1H),7.27–7.18(m,2H),7.04(s,1H),6.83–6.75(m,2H),4.32(t,2H),3.13(s,2H),2.86(t,2H),2.83(m,1H),1.22(d,6H).
5-[(4-氯苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (79)
Mp 171～173℃；ESIMS m/z：302[M+H]+；1HNMR(400MHz,CDCl3)δ11.26(s,1H),7.38–7.25(m,2H),7.04(dd,2H),7.02(s,1H),4.32(t,2H),3.13(s,2H),2.87(t,2H).
5-[(2,3-二氟苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (80)
Mp 172～174℃；ESIMS m/z：304[M+H]+；1HNMR(400MHz,CDCl3)δ11.28(s,1H),7.05(td,1H),6.98(s,1H),6.75(m,2H),4.32(t,2H),3.13(s,2H),2.85(t,2H).
5-[(2,3-二碘苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (81)
Mp 280～282℃；ESIMS m/z：520[M+H]+；1HNMR(400MHz,CDCl3)δ11.25(s,1H),7.27(dd,1H),7.17(s,1H),6.98(t,1H),6.77(dd,1H),4.33(t,2H),3.12(s,2H),2.87(t,2H).
5-[(2,4-二异丁基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (82)
Mp 210～212℃；ESIMS m/z：380[M+H]+；1HNMR(400MHz,CDCl3)δ11.29(s,1H),7.24(s,1H),7.03(dd,1H),6.94(d,1H),6.77(d,1H),4.32(t,2H),3.13(s,2H),2.84(t,2H),2.44(t,4H),2.05(m,2H),0.92(dd,12H).
5-[(2,4-二溴苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (83)
Mp 233～235℃；ESIMS m/z：426[M+H]+；1HNMR(400MHz,CDCl3)δ11.25(s,1H),7.72(d,1H),7.44(dd,1H),7.15(s,1H),6.82(d,1H),4.33(t,2H),3.12(s,2H),2.87(t,2H).
5-[(3,4-二甲基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (84)
Mp 168～170℃；ESIMS m/z：296[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.07(s,1H),7.02(d,1H),6.75–6.63(m,2H),4.32(t,2H),3.13(s,2H),2.85(t,2H),2.26(s,3H),2.23(s,3H).
5-[(3,4-二异丙基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (85)
Mp 196～198℃；ESIMS m/z：352[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.27(s,1H),7.16(d,1H),6.85(d,1H),6.67(dd,1H),4.32(t,2H),3.13(m,1H),3.11(s,2H),3.04(m,1H),2.85(t,2H),1.42(t,12H).
5-[(2,5-二叔丁基苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (86)
Mp 210～212℃；ESIMS m/z：380[M+H]+；1HNMR(400MHz,CDCl3)δ11.26(s,1H),7.25(s,1H),7.21(d,1H),6.87(dd,1H),6.84(d,1H),4.32(t,2H),3.71(s,2H),2.85(t,2H),1.37(s,9H),1.26(s,9H).
5-[(2,5-二氯苯氧乙硫基)甲基]噁唑-2(3H)-硫酮 (87)
Mp 188～190℃；ESIMS m/z：336[M+H]+；1HNMR(400MHz,CDCl3)δ11.27(s,1H),7.32(d,1H),7.14(s,1H),7.09(dd,1H),7.05(d,1H),4.33(t,2H),3.12(s,2H),2.84(t,2H).
5-(苯氧丙硫基甲基)噁唑-2(3H)-酮 (88)
Mp 143～145℃；ESIMS m/z：266[M+H]+；1HNMR(400MHz,CDCl3)δ7.30(td,2H),7.29(s,1H),6.91(tt,1H),6.90(dt,2H),5.55(s,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.41(tt,2H).
5-[(2-氟苯氧丙硫基)甲基]噁唑-2(3H)-酮 (89)
Mp 152～154℃；ESIMS m/z：284[M+H]+；1HNMR(400MHz,CDCl3)δ7.11(tt,1H),7.06(td,1H),7.03(td,1H),6.81(td,1H),6.72(s,1H),5.55(s,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H).
5-[(2-氯苯氧丙硫基)甲基]噁唑-2(3H)-酮 (90)
Mp 160～162℃；ESIMS m/z：300[M+H]+；1HNMR(400MHz,CDCl3)δ7.34(dd,1H),7.29(s,1H),7.28(dd,1H),7.26(td,1H),7.02–6.89(td,1H),5.57(s,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.42(tt,2H).
5-[(3-碘苯氧丙硫基)甲基]噁唑-2(3H)-酮 (91)
Mp 206～208℃；ESIMS m/z：392[M+H]+；1HNMR(400MHz,CDCl3)δ7.38(dt,1H),7.29(s,1H),7.27(t,1H),7.02(t,1H),6.83(dt,1H),5.55(s,1H),4.23(t,2H),3.13(s,2H),2.72(t,2H),2.41(tt,2H).
5-[(3-乙氨基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (92)
Mp 178～180℃；ESIMS m/z：337[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),7.02(t,1H),6.43(dt,1H),6.27(t,1H),6.22(td,1H),5.55(s,1H),4.21(t,2H),3.35(q,4H),3.12(s,2H),2.72(t,2H),2.44(tt,2H),1.11(t,6H).
5-[(4-甲基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (93)
Mp 150～152℃；ESIMS m/z：280[M+H]+；1HNMR(400MHz,CDCl3)δ7.33(s,1H),7.13–7.02(dd,2H),6.83–6.74(dd,2H),5.58(s,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.41(tt,2H),2.30(s,3H).
5-[(4-溴苯氧丙硫基)甲基]噁唑-2(3H)-酮 (94)
Mp 182～184℃；ESIMS m/z：344[M+H]+；1HNMR(400MHz,CDCl3)δ7.53–7.42(dd,2H),7.32(s,1H),6.90–6.80(dd,2H),5.57(s,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.45(tt,2H).
5-[(2,3-二乙基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (95)
Mp 171～173℃；ESIMS m/z：322[M+H]+；1HNMR(400MHz,CDCl3)δ7.27(s,1H),7.13(t,1H),6.77–6.68(dd,1H),6.64(dd,1H),5.63(s,1H),4.23(t,2H),3.12(s,2H),2.71(tt,2H),2.66(q,2H),2.45(q,2H),2.43(tt,2H),1.17(dt,6H).
5-[(2,3-二异丙基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (96)
Mp 185～187℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),7.14(t,1H),6.97–6.84(dd,1H),6.66(dd,1H),5.62(s,1H),4.23(t,2H),3.48–3.22(m,2H),3.12(s,2H),2.72(t,2H),2.42(tt,2H),1.31(t,12H).
5-[(2,4-二氟苯氧丙硫基)甲基]噁唑-2(3H)-酮 (97)
Mp 161～163℃；ESIMS m/z：302[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),6.93(dt,1H),6.77(td,1H),6.73(td,1H),5.65(s,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.44(tt,2H).
5-[(2,4-二氯苯氧丙硫基)甲基]噁唑-2(3H)-酮 (98)
Mp 177～179℃；ESIMS m/z：334[M+H]+；1HNMR(400MHz,CDCl3)δ7.39(d,1H),7.28(s,1H),7.26(dd,1H),7.13(d,1H),5.55(s,1H),4.23(t,2H),3.13(s,2H),2.72(t,2H),2.41(tt,2H).
5-[(2,5-二甲基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (99)
Mp 157～159℃；ESIMS m/z：294[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),6.93(d,1H),6.63(d,1H),6.55(dd,1H),5.56(s,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.44(tt,2H),2.19(s,3H),2.03(s,3H).
5-[(2,5-二溴苯氧丙硫基)甲基]噁唑-2(3H)-酮 (100)
Mp 222～224℃；ESIMS m/z：424[M+H]+；1HNMR(400MHz,CDCl3)δ7.35(d,1H),7.32(s,1H),7.11(d,1H),7.10(dd,1H),5.57(s,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H).
5-[(2,6-二异丙基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (101)
Mp 185～187℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ7.27(s,1H),7.28–7.22(m,2H),7.13(t,1H),5.55(s,1H),4.23(t,2H),3.43–3.28(m,2H),3.12(s,2H),2.73(t,2H),2.45(tt,2H),1.24(d,12H).
5-[(2,6-二叔丁基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (102)
Mp 199～201℃；ESIMS m/z：378[M+H]+；1HNMR(400MHz,CDCl3)δ7.29(s,1H),7.14(dd,2H),7.05(t,1H),5.57(s,1H),4.26(t,2H),3.12(s,2H),2.73(t,2H),2.42(tt,2H),1.34(s,18H).
5-[(苯氧丙硫基甲基)噁唑-2(3H)-硫酮 (103)
Mp 161～163℃；ESIMS m/z：282[M+H]+；1HNMR(400MHz,CDCl3)δ10.45(s,1H),7.32(dt,2H),6.91(tt,1H),6.90(td,2H),6.81(s,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H).
5-[(2-氟苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (104)
Mp 170～172℃；ESIMS m/z：300[M+H]+；1HNMR(400MHz,CDCl3)δ11.52(s,1H),7.32(s,1H),7.12(tt,1H),7.10(td,1H),7.04(td,1H),6.88(m,1H),4.23(t,2H),3.12(s,2H),2.72(t,2H),2.44(tt,2H).
5-[(2-氯苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (105)
Mp 178～180℃；ESIMS m/z：316[M+H]+；1HNMR(400MHz,CDCl3)δ11.27(s,1H),7.35(dd,1H),7.28(td,1H),7.06(dd,1H),7.03(s,1H),6.96(td,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H).
5-[(3-碘苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (106)
Mp 224～226℃；ESIMS m/z：408[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.37(dt,1H),7.25(t,1H),7.06(s,1H),7.02(t,1H),6.88(dt,1H),4.21(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H).
5-[(3-乙氨基苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (107)
Mp 196～198℃；ESIMS m/z：353[M+H]+；1HNMR(400MHz,CDCl3)δ11.28(s,1H),7.01(t,1H),6.99(s,1H),6.45(dt,1H),6.37(dt,1H),6.27(t,1H),4.23(t,2H),3.35(q,4H),3.12(s,2H),2.73(t,2H),2.44(tt,2H),1.11(t,6H).
5-[(4-甲基苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (108)
Mp 168～170℃；ESIMS m/z：296[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.07(dd,2H),7.05(s,1H),6.82(dd,2H),4.24(t,2H),3.13(s,2H),2.72(t,2H),2.44(tt,2H),2.32(s,3H).
5-[(4-溴苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (109)
Mp 201～203℃；ESIMS m/z：362[M+H]+；1HNMR(400MHz,CDCl3)δ11.33(s,1H),7.47–7.37(dd,2H),7.05(s,1H),6.94–6.82(dd,2H),4.23(t,2H),3.13(s,2H),2.72(t,2H),2.44(tt,2H).
5-[(2,3-二乙基苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (110)
Mp 189～191℃；ESIMS m/z：338[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.14(t,1H),7.03(s,1H),6.76–6.68(dd,1H),6.66(dd,1H),4.23(t,2H),3.12(s,2H),2.71(t,2H),2.66(q,2H),2.45(q,2H),2.43(tt,2H),1.23(t,3H),1.14(t,3H).
5-[(2,3-二异丙基苯氧丙硫基)甲基]噁唑-2(3H)-酮 (111)
Mp 195～197℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ7.28(s,1H),7.12(t,1H),6.93–6.87(dd,1H),6.66(dd,1H),5.62(s,1H),4.23(t,2H),3.44–3.21(m,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H),1.33(d,6H),1.31(d,6H).
5-[(2,4-二氟苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (112)
Mp 179～181℃；ESIMS m/z：318[M+H]+；1HNMR(400MHz,CDCl3)δ11.25(s,1H),6.99(s,1H),6.94(td,1H),6.81(td,1H),6.72(td,1H),4.24(t,2H),3.12(s,2H),2.72(t,2H),2.44(tt,2H).
5-[(2,4-二氯苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (113)
Mp 195～197℃；ESIMS m/z：350[M+H]+；1HNMR(400MHz,CDCl3)δ11.28(s,1H),7.36(d,1H),7.27(dd,1H),7.13(d,1H),6.99(s,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.42(tt,2H).
5-[(2,5-二甲基苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (114)
Mp 175～177℃；ESIMS m/z：310[M+H]+；1HNMR(400MHz,CDCl3)δ11.26(s,1H),7.03(s,1H),6.94(d,1H),6.63(d,1H),6.55(dd,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H),2.16(s,3H),2.03(s,3H).
5-[(2,5-二溴苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (115)
Mp 240～242℃；ESIMS m/z：440[M+H]+；1HNMR(400MHz,CDCl3)δ11.32(s,1H),7.36–7.28(d,1H),7.06(dd,1H),7.05(d,1H),7.04(s,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H).
5-[(2,6-二异丙基苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (116)
Mp 203～205℃；ESIMS m/z：366[M+H]+；1HNMR(400MHz,CDCl3)δ11.25(s,1H),7.25(dd,2H),7.17(s,1H),7.15(t,1H),4.23(t,2H),3.45–3.31(m,2H),3.12(s,2H),2.73(t,2H),2.42(tt,2H),1.21(d,12H).
5-[(2,6-二叔丁基苯氧丙硫基)甲基]噁唑-2(3H)-硫酮 (117)
Mp 217～219℃；ESIMS m/z：394[M+H]+；1HNMR(400MHz,CDCl3)δ11.28(s,1H),7.16(dd,2H),7.14(s,1H),7.06(t,1H),4.23(t,2H),3.12(s,2H),2.73(t,2H),2.41(tt,2H),1.35(s,18H).
4-(苯氧甲基)1,3-二氢咪唑-2-酮 (118)
Mp 104～106℃；ESIMS m/z：191[M+H]+；1HNMR(400MHz,CDCl3)δ8.58(s,1H),8.48(s,1H),7.15(dt,2H),6.91–6.82(dt,2H),6.84(tt,1H),6.14(s,1H),5.03(s,2H).
4-(邻甲苯氧基甲基)1,3-二氢咪唑-2-酮 (119)
Mp 111～113℃；ESIMS m/z：205[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.45(s,1H),7.05(dd,1H),7.00(dt,1H),6.87(td,1H),6.72(dd,1H),6.17(s,1H),5.06–4.96(s,2H),2.23(s,3H).
4-[(2-溴苯氧基)甲基]1,3-二氢咪唑-2-酮 (120)
Mp 144～146℃；ESIMS m/z：269[M+H]+；1HNMR(400MHz,CDCl3)δ8.79(s,1H),8.53(s,1H),7.52(dd,1H),7.25(td,1H),6.90(dd,1H),6.84(td,1H),6.17(s,1H),5.03(s,2H).
4-[(3-氯苯氧基)甲基]1,3-二氢咪唑-2-酮 (121)
Mp 122～124℃；ESIMS m/z：225[M+H]+；1HNMR(400MHz,CDCl3)δ8.58(s,1H),8.53(s,1H),7.22(t,1H),6.98(t,1H),6.96(dt,1H),6.75(dt,1H),6.16(s,1H),5.04(s,2H).
4-[(3-苯氧基苯氧基)甲基]1,3-二氢咪唑-2-酮 (122)
Mp 151～153℃；ESIMS m/z：283[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.44(s,1H),7.35(dt,2H),7.29(t,1H),7.10(tt,1H),7.02–6.92(dt,2H),6.68(dt,1H),6.51(dt,1H),6.49(t,1H),6.18(s,1H),5.06–4.96(s,2H).
4-[(4-异丙基苯氧基)甲基]1,3-二氢咪唑-2-酮 (123)
Mp 125～127℃；ESIMS m/z：233[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.45(s,1H),7.25(dd,2H),6.87–6.79(dd,2H),6.14(s,1H),5.03(s,2H),2.87(m,1H),1.21(d,6H).
4-[(4-溴苯氧基)甲基]1,3-二氢咪唑-2-酮 (124)
Mp 144～146℃；ESIMS m/z：269[M+H]+；1HNMR(400MHz,CDCl3)δ8.57(s,1H),8.47(s,1H),7.42–7.31(dd,2H),6.91–6.78(dd,2H),6.16(s,1H),5.04(s,2H).
4-[(2,3-二甲基苯氧基)甲基]1,3-二氢咪唑-2-酮 (125)
Mp 117～119℃；ESIMS m/z：219[M+H]+；1HNMR(400MHz,CDCl3)δ8.59(s,1H),8.46(s,1H),7.05(t,1H),6.62(dd,2H),6.17(s,1H),5.04(s,2H),2.22(s,3H),2.13(s,3H).
4-[(2,3-二氟苯氧基)甲基]1,3-二氢咪唑-2-酮 (126)
Mp 124～126℃；ESIMS m/z：227[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.46(s,1H),7.05(td,1H),6.74(m 2H),6.19(s,1H),5.01(s,2H).
4-[(2,4-二叔丁基苯氧基)甲基]1,3-二氢咪唑-2-酮 (127)
Mp 161～163℃；ESIMS m/z：303[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.51(s,1H),7.17(d,1H),6.96(dd,1H),6.62(d,1H),6.13(s,1H),5.02(s,2H),1.36(s,9H),1.24(s,9H).
4-[(2,4-二碘苯氧基)甲基]1,3-二氢咪唑-2-酮 (128)
Mp 230～232℃；ESIMS m/z：443[M+H]+；1HNMR(400MHz,CDCl3)δ8.65(s,1H),8.54(s,1H),7.95(d,1H),7.64(dd,1H),6.53(d,1H),6.14(s,1H),5.02(s,2H).
4-[(3,4-二甲基苯氧基)甲基]1,3-二氢咪唑-2-酮 (129)
Mp 118～120℃；ESIMS m/z：219[M+H]+；1HNMR(400MHz,CDCl3)δ8.59(s,1H),8.48(s,1H),6.96(d,1H),6.64(d,1H),6.63(dd,1H),6.15(s,1H),5.02–4.94(s,2H),2.25(s,3H),2.24(s,3H).
4-[(3,4-二氟苯氧基)甲基]1,3-二氢咪唑-2-酮 (130)
Mp 124～126℃；ESIMS m/z：227[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.52(s,1H),7.03(m,1H),6.66(m,1H),6.54(m,1H),6.13(s,1H),5.01(s,2H).
4-[(2,5-二乙基苯氧基)甲基]1,3-二氢咪唑-2-酮 (131)
Mp 133～135℃；ESIMS m/z：247[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.46(s,1H),7.15(d,1H),6.66(dd,1H),6.62(d,1H),6.18(s,1H),5.02(s,2H),2.59(q,2H),2.58(q,2H),1.22(t,3H),1.20(t,3H).
4-[(2,6-二异丙基苯氧基)甲基]1,3-二氢咪唑-2-酮 (132)
Mp 146～148℃；ESIMS m/z：275[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.46(s,1H),7.20–7.15(dd,2H),7.06(t,1H),6.12(s,1H),5.02(s,2H),3.25(m,2H),1.22(d,12H).
4-(苯氧甲基)1,3-二氢咪唑-2-硫酮 (133)
Mp 123～125℃；ESIMS m/z：207[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.42(s,1H),7.15(dt,2H),6.90–6.82(dt,2H),6.83(tt,1H),5.94(s,1H),5.02–4.92(s,2H).
4-[(邻甲苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (134)
Mp 130～132℃；ESIMS m/z：221[M+H]+；1HNMR(400MHz,CDCl3)δ9.45(s,1H),9.43(s,1H),7.03(dd,1H),7.00(td,1H),6.85(td,1H),6.72(dd,1H),5.94(s,1H),5.02(s,2H),2.23(s,3H).
4-[(2-溴苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (135)
Mp 163～165℃；ESIMS m/z：287[M+H]+；1HNMR(400MHz,CDCl3)δ9.74(s,1H),9.43(s,1H),7.51(dd,1H),7.23(td,1H),6.95(dd,1H),6.84(td,1H),5.91(s,1H),5.02(s,2H).
4-[(3-氯苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (136)
Mp 140～142℃；ESIMS m/z：241[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.44(s,1H),7.22(dd,1H),6.92(dd,2H),6.75(dt,1H),5.96(s,1H),5.04(s,2H).
4-[(3-苯氧基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (137)
Mp 168～170℃；ESIMS m/z：299[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.34(s,1H),7.36(td,2H),7.24(t,1H),7.15(tt,1H),7.06–6.95(dt,2H),6.72(dt,1H),6.53(dt,1H),6.45(t,1H),5.86(s,1H),5.01(s,2H).
4-[(4-异丙基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (138)
Mp 144～146℃；ESIMS m/z：249[M+H]+；1HNMR(400MHz,CDCl3)δ9.52(s,1H),9.41(s,1H),7.23–7.15(dd,2H),6.81–6.73(dd,2H),5.94(s,1H),5.02(s,2H),2.86(m,1H),1.23(d,6H).
4-[(4-溴苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (139)
Mp 162～164℃；ESIMS m/z：287[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.43(s,1H),7.43–7.32(dd,2H),6.93–6.83(dd,2H),5.91(s,1H),5.04(s,2H).
4-[(2,3-二甲基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (140)
Mp 136～138℃；ESIMS m/z：235[M+H]+；1HNMR(400MHz,CDCl3)δ9.45(s,1H),9.43(s,1H),7.03(t,1H),6.61(dd,2H),5.94(s,1H),5.05(s,2H),2.20(s,3H),2.19(s,3H).
4-[(2,3-二氟苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (141)
Mp 141～143℃；ESIMS m/z：243[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.44(s,1H),7.03(td,1H),6.70(td,1H),6.67(tt,1H),5.90(s,1H),5.01(s,2H).
4-[(2,4-二叔丁基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (142)
Mp 178～180℃；ESIMS m/z：319[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.44(s,1H),7.15(d,1H),6.94(dd,1H),6.68(d,1H),5.93(s,1H),5.03(s,2H),1.32(s,9H),1.25(s,9H).
4-[(2,4-二碘苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (143)
Mp 248～250℃；ESIMS m/z：459[M+H]+；1HNMR(400MHz,CDCl3)δ9.76(s,1H),9.44(s,1H),7.94(d,1H),7.56(dd,1H),6.58(d,1H),5.90(s,1H),5.03(s,2H).
4-[(3,4-二甲基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (144)
Mp 137～139℃；ESIMS m/z：235[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.42(s,1H),6.93–6.87(d,1H),6.63(d,1H),6.62(dd,1H),5.92(s,1H),5.02(s,2H),2.25(s,3H),2.23(s,3H).
4-[(3,4-二氟苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (145)
Mp 141～143℃；ESIMS m/z：243[M+H]+；1HNMR(400MHz,CDCl3)δ9.45(s,1H),9.45(s,1H),7.01(m,1H),6.66(m,1H),6.58(m,1H),5.95(s,1H),5.04(s,2H).
4-[(2,5-二乙基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (146)
Mp 151～153℃；ESIMS m/z：263[M+H]+；1HNMR(400MHz,CDCl3)δ9.43(s,1H),9.44(s,1H),7.13(d,1H),6.65(dd,1H),6.63(d,1H),5.92(s,1H),5.01(s,2H),2.59(q,2H),2.58(q,2H),1.22(dt,6H).
4-[(2,6-二异丙基苯氧基)甲基]1,3-二氢咪唑-2-硫酮 (147)
Mp 164～166℃；ESIMS m/z：291[M+H]+；1HNMR(400MHz,CDCl3)δ9.43(s,1H),9.31(s,1H),7.23–7.17(dd,2H),7.04(t,1H),5.96(s,1H),5.02(s,2H),3.42–3.29(m,2H),1.23(d,12H).
4-(苯氧甲硫基甲基)1,3-二氢咪唑-2-酮 (148)
Mp 127～129℃；ESIMS m/z：237[M+H]+；1HNMR(400MHz,CDCl3)δ9.03(s,1H),8.47(s,1H),7.34(td,2H),7.00–6.93(dt,2H),6.94(tt,1H),6.02(s,1H),5.06(s,2H),3.53(s,2H).
4-[(2-乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (149)
Mp 142～144℃；ESIMS m/z：265[M+H]+；1HNMR(400MHz,CDCl3)δ8.74(s,1H),8.55(s,1H),7.22–7.15(dd,1H),7.11(td,1H),7.04(td,1H),6.72(dd,1H),6.01(s,1H),5.06(s,2H),3.52(s,2H),2.58(m,2H),1.16(t,3H).
4-[(2-氟苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (150)
Mp 136～138℃；ESIMS m/z：255[M+H]+；1HNMR(400MHz,CDCl3)δ8.63(s,1H),8.45(s,1H),7.11(tt,1H),7.08(dt,1H),7.03(dt,1H),6.96(dt,1H),5.95(s,1H),5.06(s,2H),3.52(s,2H).
4-(间甲苯氧基甲硫基甲基)1,3-二氢咪唑-2-酮 (151)
Mp 134～136℃；ESIMS m/z：251[M+H]+；1HNMR(400MHz,CDCl3)δ8.65(s,1H),8.53(s,1H),7.21(t,1H),6.78(dt,1H),6.76(dt,1H),6.74(t,1H),5.95(s,1H),5.06(s,2H),3.53(s,2H),2.34(s,3H).
4-[(3-乙氨基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (152)
Mp 150～152℃；ESIMS m/z：280[M+H]+；1HNMR(400MHz,CDCl3)δ8.61(s,1H),8.43(s,1H),7.07(t,1H),6.32(dt,1H),6.29(dt,1H),6.20(t,1H),5.99(s,1H),5.06(s,2H),4.35(s,1H),3.55(s,2H),3.32(q,2H),1.24(t,3H).
4-[(4-乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (153)
Mp 142～144℃；ESIMS m/z：265[M+H]+；1HNMR(400MHz,CDCl3)δ8.83(s,1H),8.46(s,1H),7.17(dd,2H),6.86–6.76(dd,2H),6.03(s,1H),5.05(s,2H),3.55(s,2H),2.70(q,2H),1.18(t,3H).
4-[(4-氯苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (154)
Mp 144～146℃；ESIMS m/z：271[M+H]+；1HNMR(400MHz,CDCl3)δ8.63(s,1H),8.41(s,1H),7.33–7.23(dd,2H),6.84–6.74(dd,2H),5.99(s,1H),5.06(s,2H),3.52(s,2H).
4-[(2,3-二乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (155)
Mp 155～157℃；ESIMS m/z：293[M+H]+；1HNMR(400MHz,CDCl3)δ8.73(s,1H),8.44(s,1H),7.11(t,1H),6.74(dd,1H),6.64(dd,1H),5.94(s,1H),5.05(s,2H),3.55(s,2H),2.61(q,2H),2.42(q,2H),1.23(t,3H),1.13(t,3H).
4-[(2,3-二溴苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (156)
Mp 205～207℃；ESIMS m/z：395[M+H]+；1HNMR(400MHz,CDCl3)δ8.62(s,1H),8.45(s,1H),7.36(dd,1H),7.17(t,1H),7.07(dd,1H),5.96(s,1H),5.05(s,2H),3.51(s,2H).
4-[(2,4-二甲基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (157)
Mp 142～144℃；ESIMS m/z：265[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.44(s,1H),7.04(d,1H),6.97(dd,1H),6.71(d,1H),5.94(s,1H),5.05(s,2H),3.52(s,2H),2.37(s,3H),2.20(s,3H).
4-[(2,4-二氟苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (158)
Mp 145～147℃；ESIMS m/z：273[M+H]+；1HNMR(400MHz,CDCl3)δ8.54(s,1H),8.44(s,1H),6.96(dt,1H),6.80(td,1H),6.71(m,1H),5.96(s,1H),5.04(s,2H),3.51(s,2H).
4-[(3,4-二乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (159)
Mp 155～157℃；ESIMS m/z：293[M+H]+；1HNMR(400MHz,CDCl3)δ8.69(s,1H),8.47(s,1H),7.05(d,1H),6.76(dd,1H),6.74(d,1H),5.96(s,1H),5.08(s,2H),3.51(s,2H),2.48(m,4H),1.18(t,3H),1.17(t,3H).
4-[(3,4-二氯苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (160)
Mp 161～163℃；ESIMS m/z：305[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.45(s,1H),7.30(d,1H),6.97(d,1H),6.73(dd,1H),5.96(s,1H),5.06(s,2H),3.53(s,2H).
4-[(2,5-二异丙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (161)
Mp 170～172℃；ESIMS m/z：321[M+H]+；1HNMR(400MHz,CDCl3)δ8.71(s,1H),8.61(s,1H),7.24(d,1H),7.06(dd,1H),6.81–6.74(d,1H),6.11(s,1H),5.06(s,2H),3.52(s,2H),3.25(m,1H),3.01–2.89(m,1H),1.24(d,6H),1.23(d,6H).
4-[(2,5-二溴苯氧甲硫基)甲基]1,3-二氢咪唑-2-酮 (162)
Mp 205～207℃；ESIMS m/z：395[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.45(s,1H),7.38(d,1H),7.12(d,1H),7.11(dd,1H),5.96(s,1H),5.06(s,2H),3.51(s,2H).
4-(苯氧甲硫基甲基)1,3-二氢咪唑-2-硫酮 (163)
Mp 145～147℃；ESIMS m/z：253[M+H]+；1HNMR(400MHz,CDCl3)δ10.12(s,1H),9.40(s,1H),7.31–7.21(dt,2H),6.90(m,3H),5.77(s,1H),5.06(s,2H),3.54(s,2H).
4-[(2-乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (164)
Mp 160～162℃；ESIMS m/z：281[M+H]+；1HNMR(400MHz,CDCl3)δ9.62(s,1H),9.52(s,1H),7.34–7.27(dd,1H),7.11(dt,2H),6.88(dd,1H),5.81(s,1H),5.06(s,2H),3.52(s,2H),2.55(q,2H),1.27(t,3H).
4-[(2-氟苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (165)
Mp 154～156℃；ESIMS m/z：271[M+H]+；1HNMR(400MHz,CDCl3)δ9.55(s,1H),9.36(s,1H),7.11(tt,1H),7.08(dt,1H),7.03(dt,1H),6.96(dt,1H),5.74(s,1H),5.05(s,2H),3.51(s,2H).
4-(间甲苯氧甲硫基甲基)1,3-二氢咪唑-2-硫酮 (166)
Mp 153～155℃；ESIMS m/z：267[M+H]+；1HNMR(400MHz,CDCl3)δ9.55(s,1H),9.44(s,1H),7.25(t,1H),6.83(dt,1H),6.79(t,1H),6.78(dt,1H),5.73(s,1H),5.06(s,2H),3.52(s,2H),2.30(s,3H).
4-[(3-乙氨基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (167)
Mp 167～169℃；ESIMS m/z：296[M+H]+；1HNMR(400MHz,CDCl3)δ9.56(s,1H),9.35(s,1H),7.07(t,1H),6.28(dt,2H),6.26(t,1H),5.73(s,1H),5.06(s,2H),4.32(s,1H),3.51(s,2H),3.34(q,2H),1.24(t,3H).
4-[(4-乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (168)
Mp 160～162℃；ESIMS m/z：281[M+H]+；1HNMR(400MHz,CDCl3)δ9.66(s,1H),9.44(s,1H),7.18–7.10(dd,2H),6.81–6.72(dd,2H),5.77(s,1H),5.06(s,2H),3.52(s,2H),2.72(q,2H),1.16(t,3H).
4-[(4-氯苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (169)
Mp 162～164℃；ESIMS m/z：287[M+H]+；1HNMR(400MHz,CDCl3)δ9.55(s,1H),9.38(s,1H),7.33–7.23(dd,2H),6.85–6.76(dd,2H),5.74(s,1H),5.07(s,2H),3.51(s,2H).
4-[(2,3-二乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (170)
Mp 174～176℃；ESIMS m/z：309[M+H]+；1HNMR(400MHz,CDCl3)δ9.81(s,1H),9.47(s,1H),7.16(t,1H),6.87–6.79(dd,1H),6.62(dd,1H),5.76(s,1H),5.08(s,2H),3.53(s,2H),2.65(q,2H),2.43(q,2H),1.25(t,3H),1.16(t,3H).
4-[(2,3-二溴苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (171)
Mp 224～226℃；ESIMS m/z：411[M+H]+；1HNMR(400MHz,CDCl3)δ9.52(s,1H),9.37(s,1H),7.35(dd,1H),7.14(t,1H),7.03(dd,1H),5.71(s,1H),5.05(s,2H),3.54(s,2H).
4-[(2,4-二甲基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (172)
Mp 160～162℃；ESIMS m/z：281[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.36(s,1H),7.03–6.97(d,1H),6.96(dd,1H),6.72(d,1H),5.75(s,1H),5.06(s,2H),3.51(s,2H),2.34(s,3H),2.25(s,3H).
4-[(2,4-二氟苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (173)
Mp 164～166℃；ESIMS m/z：289[M+H]+；1HNMR(400MHz,CDCl3)δ9.53(s,1H),9.36(s,1H),6.97(dt,1H),6.81(td,1H),6.70(m,1H),5.72(s,1H),5.06(s,2H),3.53(s,2H).
4-[(3,4-二乙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (174)
Mp 174～176℃；ESIMS m/z：309[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.36(s,1H),7.07–7.00(d,1H),6.76(d,1H),6.65(dd,1H),5.74(s,1H),5.07(s,2H),3.51(s,2H),2.43(q,4H),1.18(t,3H),1.16(t,3H).
4-[(3,4-二氯苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (175)
Mp 180～182℃；ESIMS m/z：321[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.39(s,1H),7.30(d,1H),6.94(d,1H),6.67(dd,1H),5.76(s,1H),5.05(s,2H),3.54(s,2H).
4-[(2,5-二异丙基苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (176)
Mp 187～189℃；ESIMS m/z：337[M+H]+；1HNMR(400MHz,CDCl3)δ9.55(s,1H),9.35(s,1H),7.23(d,1H),6.95(dd,1H),6.88(d,1H),5.71–5.66(s,1H),5.06(s,2H),3.52(s,2H),3.21(m,1H),2.93(m,1H),1.24(d,6H),1.23(d,6H).
4-[(2,5-二溴苯氧甲硫基)甲基]1,3-二氢咪唑-2-硫酮 (177)
Mp 224～226℃；ESIMS m/z：411[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.34(s,1H),7.39(d,1H),7.20(d,1H),7.14(dd,1H),5.72(s,1H),5.07(s,2H),3.52(s,2H).
4-(苯氧乙硫基甲基)1,3-二氢咪唑-2-酮 (178)
Mp 134～136℃；ESIMS m/z：251[M+H]+；1HNMR(400MHz,CDCl3)δ8.50(s,1H),8.42(s,1H),7.34–7.23(dt,2H),6.94(m,3H),5.94(s,1H),4.30(t,2H),3.53(s,2H),2.84(t,2H).
4-[(3-乙基苯氧基乙硫基)甲基]1,3-二氢咪唑-2-酮 (179)
Mp 148～150℃；ESIMS m/z：279[M+H]+；1HNMR(400MHz,CDCl3)δ9.23(s,1H),8.54(s,1H),7.22(t,1H),7.10–7.02(td,1H),6.84(dt,1H),6.73(t,1H),6.05(s,1H),4.30(t,2H),3.53(s,2H),2.84(t,2H),2.61–2.49(q,2H),1.25(t,3H).
4-[(3-氟苯氧基乙硫基)甲基]1,3-二氢咪唑-2-酮 (180)
Mp 144～146℃；ESIMS m/z：269[M+H]+；1HNMR(400MHz,CDCl3)δ9.21(s,1H),8.54(s,1H),7.32(dt,1H),7.29(dt,1H),6.93(m,1H),6.61(dt,1H),6.00(s,1H),4.35(t,2H),3.55(s,2H),2.82(t,2H).
4-(对甲苯氧基乙硫基甲基)1,3-二氢咪唑-2-酮 (181)
Mp 142～144℃；ESIMS m/z：265[M+H]+；1HNMR(400MHz,CDCl3)δ8.65(s,1H),8.46(s,1H),7.10–7.01(dd,2H),6.85–6.75(dd,2H),5.96(s,1H),4.34(t,2H),3.51(s,2H),2.85(t,2H),2.34(s,3H).
4-[(4-碘苯氧基乙硫基)甲基]1,3-二氢咪唑-2-酮 (182)
Mp 198～200℃；ESIMS m/z：377[M+H]+；1HNMR(400MHz,CDCl3)δ8.66(s,1H),8.56(s,1H),7.71–7.61(dd,2H),6.64–6.52(dd,2H),6.14(s,1H),4.33(t,2H),3.53(s,2H),2.84(t,2H).
4-[(4-苄硫基苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (183)
Mp 196～198℃；ESIMS m/z：373[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.46(s,1H),7.55–7.45(dd,2H),7.41–7.32(td,2H),7.24(td,2H),7.21–7.12(tt,1H),6.84–6.73(dd,2H),5.95(s,1H),4.33(s,2H),4.31(t,2H),3.52(s,2H),2.87(t,2H).
4-[(2,3-二异丙基苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (184)
Mp 177～179℃；ESIMS m/z：335[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.43(s,1H),7.18(t,1H),6.94(dd,1H),6.78(dd,1H),5.96(s,1H),4.34(t,2H),3.51(s,2H),3.45–3.29(m,2H),2.83(t,2H),1.36(d,6H),1.34(d,6H).
4-[(2,3-二氯苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (185)
Mp 168～170℃；ESIMS m/z：319[M+H]+；1HNMR(400MHz,CDCl3)δ8.66(s,1H),8.51(s,1H),7.42(dd,1H),7.23(t,1H),7.08(dd,1H),6.03(s,1H),4.30(t,2H),3.52(s,2H),2.82(t,2H).
4-[(2,4-二氯苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (186)
Mp 168～170℃；ESIMS m/z：319[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.45(s,1H),7.35(d,1H),7.24(dd,1H),7.15(d,1H),5.96(s,1H),4.34(t,2H),3.52(s,2H),2.84(t,2H).
4-[(3,4-二溴苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (187)
Mp 213～215℃；ESIMS m/z：409[M+H]+；1HNMR(400MHz,CDCl3)δ8.57(s,1H),8.43(s,1H),7.45(d,1H),7.04(d,1H),6.61(dd,1H),5.98(s,1H),4.34(t,2H),3.52(s,2H),2.84(t,2H).
4-[(2,5-二甲基苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (188)
Mp 148～150℃；ESIMS m/z：279[M+H]+；1HNMR(400MHz,CDCl3)δ8.53(s,1H),8.47(s,1H),6.91(d,1H),6.63(d,1H),6.54(dd,1H),5.94(s,1H),4.33(t,2H),3.51(s,2H),2.82(t,2H),2.19(s,3H),2.06(s,3H).4-[(2,5-二氟苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (189)
Mp 152～154℃；ESIMS m/z：287[M+H]+；1HNMR(400MHz,CDCl3)δ8.66(s,1H),8.51(s,1H),7.01(m,1H),6.81(dt,1H),6.76(tt,1H),6.03(s,1H),4.35(t,2H),3.52(s,2H),2.84(t,2H).
4-[(2,6-二氟苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (190)
Mp 152～154℃；ESIMS m/z：287[M+H]+；1HNMR(400MHz,CDCl3)δ9.24(s,1H),8.53(s,1H),7.11(tt,1H),6.95–6.83(dt,2H),6.03(s,1H),4.34(t,2H),3.51(s,2H),2.83(t,2H).
4-[(2,6-二溴苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (191)
Mp 212～214℃；ESIMS m/z：409[M+H]+；1HNMR(400MHz,CDCl3)δ8.54(s,1H),8.42(s,1H),7.59(dd,2H),6.92(t,1H),6.03(s,1H),4.35(t,2H),3.54(s,2H),2.85(t,2H).
4-[(2,6-二碘苯氧乙硫基)甲基]1,3-二氢咪唑-2-酮 (192)
Mp 260～262℃；ESIMS m/z：503[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.47(s,1H),7.71(dd,2H),6.67(t,1H),6.03(s,1H),4.34(t,2H),3.52(s,2H),2.85(t,2H).
4-(苯氧乙硫基甲基)1,3-二氢咪唑-2-硫酮 (193)
Mp 152～154℃；ESIMS m/z：267[M+H]+；1HNMR(400MHz,CDCl3)δ9.41(s,1H),9.35(s,1H),7.38–7.25(dt,2H),6.90(m,3H),5.79(s,1H),4.33(t,2H),3.54(s,2H),2.83(t,2H).
4-[(3-乙基苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (194)
Mp 166～168℃；ESIMS m/z：295[M+H]+；1HNMR(400MHz,CDCl3)δ10.16(s,1H),9.43(s,1H),7.27(t,1H),7.03(dt,1H),6.85(dt,1H),6.68(t,1H),5.74(s,1H),4.33(t,2H),3.54(s,2H),2.84(t,2H),2.67–2.55(q,2H),1.24(t,3H).
4-[(3-氟苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (195)
Mp 162～164℃；ESIMS m/z：285[M+H]+；1HNMR(400MHz,CDCl3)δ9.65(s,1H),9.46(s,1H),7.23(td,1H),6.92(m,1H),6.73(dt,1H),6.55(dt,1H),5.76(s,1H),4.34(t,2H),3.51(s,2H),2.83(t,2H).
4-(对甲苯氧乙硫基甲基)1,3-二氢咪唑-2-硫酮 (196)
Mp 160～162℃；ESIMS m/z：281[M+H]+；1HNMR(400MHz,CDCl3)δ9.74(s,1H),9.35(s,1H),7.10–7.02(dd,2H),6.76–6.67(dd,2H),5.74(s,1H),4.34(t,2H),3.52(s,2H),2.83(t,2H),2.35(s,3H).
4-[(4-碘苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (197)
Mp 215～217℃；ESIMS m/z：393[M+H]+；1HNMR(400MHz,CDCl3)δ9.66(s,1H),9.35(s,1H),7.71–7.58(dd,2H),6.65–6.52(dd,2H),5.72(s,1H),4.34(t,2H),3.52(s,2H),2.83(t,2H).
4-[(4-苄硫基苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (198)
Mp 214～216℃；ESIMS m/z：389[M+H]+；1HNMR(400MHz,CDCl3)δ9.64(s,1H),8.94(s,1H),7.38(dd,4H),7.24(dt,2H),7.22–7.13(tt,1H),6.81–6.67(dd,2H),5.64(s,1H),4.31(s,2H),4.30(t,2H),3.52(s,2H),2.84(t,2H).
4-[(2,3-二异丙基苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (199)
Mp 194～196℃；ESIMS m/z：351[M+H]+；1HNMR(400MHz,CDCl3)δ9.35(s,1H),9.30(s,1H),7.18(t,1H),6.95–6.89(dd,1H),6.71(dd,1H),5.87(s,1H),4.34(t,2H),3.54(m,1H),3.52(s,2H),3.07(m,1H),2.87(t,2H),1.31(d,6H),1.29(d,6H).
4-[(2,3-二氯苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (200)
Mp 186～188℃；ESIMS m/z：335[M+H]+；1HNMR(400MHz,CDCl3)δ9.62(s,1H),9.41(s,1H),7.47(dd,1H),7.20(t,1H),6.93(dd,1H),5.76(s,1H),4.33(t,2H),3.51(s,2H),2.84(t,2H).
4-[(2,4-二氯苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (201)
Mp 186～188℃；ESIMS m/z：335[M+H]+；1HNMR(400MHz,CDCl3)δ9.43(s,1H),9.42(s,1H),7.35(d,1H),7.24(dd,1H),7.03(d,1H),5.79(s,1H),4.32(t,2H),3.52(s,2H),2.84(t,2H).
4-[(3,4-二溴苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (202)
Mp 231～233℃；ESIMS m/z：425[M+H]+；1HNMR(400MHz,CDCl3)δ9.36(s,1H),9.35(s,1H),7.41(d,1H),6.90(d,1H),6.66(dd,1H),5.79(s,1H),4.34(t,2H),3.53(s,2H),2.84(t,2H).
4-[(2,5-二甲基苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (203)
Mp 167～169℃；ESIMS m/z：295[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.35(s,1H),6.92–6.86(d,1H),6.58(d,1H),6.57(dd,1H),5.71(s,1H),4.33(t,2H),3.52(s,2H),2.84(t,2H),2.19(s,3H),2.01(s,3H).
4-[(2,5-二氟苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (204)
Mp 170～172℃；ESIMS m/z：303[M+H]+；1HNMR(400MHz,CDCl3)δ9.45(s,1H),9.35(s,1H),7.04(m,1H),6.80(dt,1H),6.75(tt,1H),5.76(s,1H),4.34(t,2H),3.52(s,2H),2.85(t,2H).
4-[(2,6-二氟苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (205)
Mp 170～172℃；ESIMS m/z：303[M+H]+；1HNMR(400MHz,CDCl3)δ9.61(s,1H),9.32(s,1H),7.06(tt,1H),6.85–6.73(dt,2H),5.76(s,1H),4.34(t,2H),3.52(s,2H),2.83(t,2H).
4-[(2,6-二溴苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (206)
Mp 230～232℃；ESIMS m/z：425[M+H]+；1HNMR(400MHz,CDCl3)δ9.65(s,1H),9.43(s,1H),7.53(dd,2H),6.95(t,1H),5.81(s,1H),4.34(t,2H),3.52(s,2H),2.82(t,2H).
4-[(2,6-二碘苯氧乙硫基)甲基]1,3-二氢咪唑-2-硫酮 (207)
Mp 277～279℃；ESIMS m/z：519[M+H]+；1HNMR(400MHz,CDCl3)δ9.68(s,1H),9.44(s,1H),7.75(dd,2H),6.61(t,1H),5.78(s,1H),4.33(t,2H),3.54(s,2H),2.85(t,2H).
4-(苯氧基丙硫基甲基)1,3-二氢咪唑-2-酮 (208)
Mp 142～144℃；ESIMS m/z：265[M+H]+；1HNMR(400MHz,CDCl3)δ8.65(s,1H),8.47(s,1H),7.31(dt,2H),6.91(tt,1H),6.90(dt,2H),6.04(s,1H),4.24(t,2H),3.52(s,2H),2.74(t,2H),2.45(tt,2H).
4-[(2-氯苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (209)
Mp 158～160℃；ESIMS m/z：299[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.44(s,1H),7.35(dd,1H),7.27(td,1H),7.25(dd,1H),6.98(td,1H),5.93(s,1H),4.25(t,2H),3.52(s,2H),2.70(t,2H),2.45(tt,2H).
4-[(2-碘苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (210)
Mp 204～206℃；ESIMS m/z：391[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.44(s,1H),7.68(dd,1H),7.23(td,1H),6.75(dd,1H),6.73(td,1H),5.95(s,1H),4.25(t,2H),3.51(s,2H),2.75(t,2H),2.41(tt,2H).
4-[(2-甲氨基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (211)
Mp 163～165℃；ESIMS m/z：308[M+H]+；1HNMR(400MHz,CDCl3)δ8.65(s,1H),8.48(s,1H),6.92(td,1H),6.93(dd,1H),6.87(dd,1H),6.66(td,1H),6.03(s,1H),4.20(t,2H),3.51(s,2H),2.92(s,6H),2.74(t,2H),2.41(tt,2H).
4-[(3-异丙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (212)
Mp 163～165℃；ESIMS m/z：307[M+H]+；1HNMR(400MHz,CDCl3)δ8.67(s,1H),8.55(s,1H),7.23(t,1H),7.01–6.96(td,1H),6.81(dt,1H),6.76(t,1H),6.05(s,1H),4.24(t,2H),3.51(s,2H),2.96–2.83(m,1H),2.75(t,2H),2.46(tt,2H),1.25(d,6H).
4-[(3-溴苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (213)
Mp 182～184℃；ESIMS m/z：345[M+H]+；1HNMR(400MHz,CDCl3)δ8.56(s,1H),8.47(s,1H),7.35(dt,1H),7.18(t,1H),7.04(t,1H),6.85(dt,1H),5.94(s,1H),4.23(t,2H),3.52(s,2H),2.75(t,2H),2.44(tt,2H).
4-[(4-叔丁基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (214)
Mp 170～172℃；ESIMS m/z：321[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.47(s,1H),7.37–7.29(dd,2H),6.86–6.76(dd,2H),5.99(s,1H),4.25(t,2H),3.52(s,2H),2.75(t,2H),2.44(tt,2H),1.25(s,9H).
4-[(4-氟苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (215)
Mp 151～153℃；ESIMS m/z：283[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.47(s,1H),7.11–6.99(dd,2H),6.84–6.74(dd,2H),5.95(s,1H),4.24(t,2H),3.53(s,2H),2.75(t,2H),2.41(tt,2H).
4-[(2,3-二碘苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (216)
Mp 267～269℃；ESIMS m/z：517[M+H]+；1HNMR(400MHz,CDCl3)δ8.58(s,1H),8.44(s,1H),7.28(dd,1H),6.95(t,1H),6.78(dd,1H),5.95(s,1H),4.21(t,2H),3.51(s,2H),2.74(t,2H),2.41(tt,2H).
4-[(2,4-二乙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (217)
Mp 170～172℃；ESIMS m/z：321[M+H]+；1HNMR(400MHz,CDCl3)δ8.57(s,1H),8.44(s,1H),7.03(dd,1H),6.96(d,1H),6.76(d,1H),5.94(s,1H),4.25(t,2H),3.51(s,2H),2.75(t,2H),2.56(q,2H),2.45(tt,2H),2.32–2.20(q,2H),1.29(t,3H),1.23(t,3H).
4-[(2,4-二异丙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (218)
Mp 184～186℃；ESIMS m/z：349[M+H]+；1HNMR(400MHz,CDCl3)δ8.52(s,1H),8.47(s,1H),7.11(d,1H),7.03(dd,1H),6.74(d,1H),6.05(s,1H),4.24(t,2H),3.53(s,2H),3.06(m,1H),2.95–2.81(m,1H),2.75(t,2H),2.41(tt,2H),1.24(d,6H),1.22(d,6H).
4-[(2,4-二溴苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (219)
Mp 220～222℃；ESIMS m/z：423[M+H]+；1HNMR(400MHz,CDCl3)δ8.58(s,1H),8.44(s,1H),7.71(d,1H),7.41(dd,1H),6.79(d,1H),5.94(s,1H),4.25(t,2H),3.52(s,2H),2.74(t,2H),2.41(tt,2H).
4-[(2,6-二甲基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (220)
Mp 155～157℃；ESIMS m/z：293[M+H]+；1HNMR(400MHz,CDCl3)δ8.84(s,1H),8.52(s,1H),7.06(t,1H),7.04(dd,2H),6.04(s,1H),4.24(t,2H),3.51(s,2H),2.75(t,2H),2.42(tt,2H),2.35(s,6H).
4-[(2,6-二乙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (221)
Mp 170～172℃；ESIMS m/z：321[M+H]+；1HNMR(400MHz,CDCl3)δ8.57(s,1H),8.44(s,1H),7.21–7.16(dd,2H),7.13–7.07(t,1H),5.94(s,1H),4.26(t,2H),3.52(s,2H),2.75(t,2H),2.56(q,4H),2.41(tt,2H),1.16(t,6H).
4-[(2,6-二氯苯氧丙硫基)甲基]1,3-二氢咪唑-2-酮 (222)
Mp 175～177℃；ESIMS m/z：333[M+H]+；1HNMR(400MHz,CDCl3)δ8.55(s,1H),8.42(s,1H),7.37(dd,2H),7.14(t,1H),5.96(s,1H),4.25(t,2H),3.52(s,2H),2.75(t,2H),2.42(tt,2H).
4-(苯氧基丙硫基甲基)1,3-二氢咪唑-2-硫酮 (223)
Mp 160～162℃；ESIMS m/z：281[M+H]+；1HNMR(400MHz,CDCl3)δ9.45(s,1H),9.39(s,1H),7.31(dt,2H),6.91(tt,1H),6.90(dt,2H),5.71(s,1H),4.24(t,2H),3.53(s,2H),2.70(t,2H),2.45(tt,2H).
4-[(2-氯苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (224)
Mp 177～179℃；ESIMS m/z：315[M+H]+；1HNMR(400MHz,CDCl3)δ9.55(s,1H),9.37(s,1H),7.35(dd,1H),7.23(td,1H),7.16(dd,1H),6.96(td,1H),5.74(s,1H),4.21(t,2H),3.53(s,2H),2.75(t,2H),2.48(tt,2H).
4-[(2-碘苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (225)
Mp 222～224℃；ESIMS m/z：407[M+H]+；1HNMR(400MHz,CDCl3)δ9.56(s,1H),9.41(s,1H),7.73(dd,1H),7.24(td,1H),6.81(dd,1H),6.72(td,1H),5.77(s,1H),4.25(t,2H),3.52(s,2H),2.70(t,2H),2.44(tt,2H).
4-[(2-甲氨基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (226)
Mp 182～184℃；ESIMS m/z：324[M+H]+；1HNMR(400MHz,CDCl3)δ9.61(s,1H),9.42(s,1H),6.96(td,1H),6.89(dd,1H),6.86(dd,1H),6.61(td,1H),5.82(s,1H),4.25(t,2H),3.51(s,2H),2.91(s,6H),2.73(t,2H),2.42(tt,2H).
4-[(3-异丙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (227)
Mp 181～183℃；ESIMS m/z：323[M+H]+；1HNMR(400MHz,CDCl3)δ9.63(s,1H),9.45(s,1H),7.20(t,1H),6.94(dt,1H),6.86(dt,1H),6.80(t,1H),5.73(s,1H),4.23(t,2H),3.53(s,2H),2.91(m,1H),2.74(t,2H),2.40(tt,2H),1.28(d,6H).
4-[(3-溴苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (228)
Mp 200～202℃；ESIMS m/z：361[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.34(s,1H),7.37(dt,1H),7.15(t,1H),7.04(t,1H),6.84(dt,1H),5.73(s,1H),4.21(t,2H),3.53(s,2H),2.75(t,2H),2.45(tt,2H).
4-[(4-叔丁基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (229)
Mp 187～189℃；ESIMS m/z：337[M+H]+；1HNMR(400MHz,CDCl3)δ9.47(s,1H),9.34(s,1H),7.38–7.32(dd,2H),6.86–6.81(dd,2H),5.75(s,1H),4.21(t,2H),3.53(s,2H),2.74(t,2H),2.44(tt,2H),1.25(s,9H).
4-[(4-氟苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (230)
Mp 168～170℃；ESIMS m/z：299[M+H]+；1HNMR(400MHz,CDCl3)δ9.63(s,1H),9.48(s,1H),7.08–6.96(dd,2H),6.84–6.73(dd,2H),5.75(s,1H),4.24(t,2H),3.54(s,2H),2.75(t,2H),2.41(tt,2H).
4-[(2,3-二碘苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (231)
Mp 285～287℃；ESIMS m/z：533[M+H]+；1HNMR(400MHz,CDCl3)δ9.64(s,1H),9.43(s,1H),7.33(dd,1H),6.95(t,1H),6.74(dd,1H),5.78(s,1H),4.25(t,2H),3.52(s,2H),2.75(t,2H),2.42(tt,2H).
4-[(2,4-二乙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (232)
Mp 187～189℃；ESIMS m/z：337[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.38(s,1H),7.05(dd,1H),6.94(d,1H),6.75(d,1H),5.71(s,1H),4.21(t,2H),3.52(s,2H),2.74(t,2H),2.55(q,2H),2.44(tt,2H),2.36–2.23(q,2H),1.25(t,3H),1.16(t,3H).
4-[(2,4-二异丙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (233)
Mp 202～204℃；ESIMS m/z：365[M+H]+；1HNMR(400MHz,CDCl3)δ9.46(s,1H),9.39(s,1H),7.14(d,1H),7.03(dd,1H),6.73(d,1H),5.73(s,1H),4.25(t,2H),3.55(s,2H),3.21(m,1H),2.84(m,1H),2.75(t,2H),2.44(tt,4.8Hz,2H),1.23(d,6H),1.22(d,6H).
4-[(2,4-二溴苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (234)
Mp 238～240℃；ESIMS m/z：439[M+H]+；1HNMR(400MHz,CDCl3)δ9.58(s,1H),9.44(s,1H),7.75(d,1H),7.40(dd,1H),6.84(d,1H),5.79(s,1H),4.21(t,2H),3.52(s,2H),2.74(t,2H),2.44(tt,2H).
4-[(2,6-二甲基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (235)
Mp 174～176℃；ESIMS m/z：309[M+H]+；1HNMR(400MHz,CDCl3)δ9.45(s,1H),9.34(s,1H),7.06(t,1H),7.03(dd,2H),5.75(s,1H),4.21(t,2H),3.53(s,2H),2.75(t,2H),2.41(tt,2H),2.24(s,6H).
4-[(2,6-二乙基苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (236)
Mp 187～189℃；ESIMS m/z：337[M+H]+；1HNMR(400MHz,CDCl3)δ9.48(s,1H),9.35(s,1H),7.21–7.15(dd,2H),7.12–7.06(t,1H),5.75(s,1H),4.23(t,2H),3.53(s,2H),2.75(t,2H),2.56(q,4H),2.44(tt,2H),1.16(t,6H).
4-[(2,6-二氯苯氧丙硫基)甲基]1,3-二氢咪唑-2-硫酮 (237)
Mp 194～196℃；ESIMS m/z：349[M+H]+；1HNMR(400MHz,CDCl3)δ9.44(s,1H),9.38(s,1H),7.38(dd,2H),7.15(t,1H),5.71(s,1H),4.25(t,2H),3.54(s,2H),2.75(t,2H),2.41(tt,2H)。
Claims (8)
1.一类苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物，其特征在于具有如下结构通式：
其中，n＝0-3的整数，X代表CH2或SCH2，Y＝O或S，Z代表O或NH，R1、R2、R3、R4和R5相同或不同，代表H、C1-C6的烷基、卤素基团、OR、SR、NHR、N(R)2中的一种或几种，其中R为C1-C6的烷基。
2.根据权利要求1所述的苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物，其特征在于所述C1-C6烷基选自Me、Et、i-Pr或t-Bu。
3.根据权利要求1所述的苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物，其特征在于R1、R2、R3、R4和R5代表H，
或者，R1、R2、R3、R4和R5其中任意一个或两个基团代表Me、Et、i-Pr、t-Bu、F、Cl、Br、I、OR、SR、NHR或N(R)2，其中R为Me、Et或Bn，R1、R2、R3、R4和R5中的其余基团为H。
4.根据权利要求3所述的苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物，其特征在于n＝1-3的整数，X代表SCH2，Y＝O或S。
5.权利要求1-4任一项所述的苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物的制备方法，其特征在于包括下列步骤：
(1)2-R1-3-R2-4-R3-5-R4-6-R5取代苯酚在碱性条件下与ω-溴代羧酸乙酯O-烃基化反应得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)羧酸乙酯(Ⅱ)，其中X＝CH2，n＝0-3，
或者(1)’将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基溴在碱性条件下与巯基羧酸乙酯发生S-烃基化反应，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)羧酸乙酯(Ⅱ)，其中X＝SCH2，n＝1-3，
(2)将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-2-烷酮(Ⅱ)与N-溴代丁二酰亚胺发生羰基α-H溴代反应，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(IⅤ)，
(3)ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(IⅤ)与氨基甲酸乙酯或O-乙基硫代氨基甲酸酯发生N-烃基化反应，得到ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-乙氧甲酰氨基-2-烷酮(V)，继而在碱性条件下发生环化反应，得到5-[ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基]-1,3-噁唑-2(3H)-酮/硫酮(I，Z＝O，Y＝O或S)，
或者(3)’将ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)-1-溴-2-烷酮(Ⅳ)与尿素或硫脲发生环化反应，得到4-[ω-(2-R1-3-R2-4-R3-5-R4-6-R5取代苯氧基)烷基]-1,3-二氢咪唑-2-酮/硫酮(I，Z＝NH，Y＝O或S)，
上述各步所述R1、R2、R3、R4、R5的定义与通式I中所述的定义相同。
6.权利要求1-4任一项所述的苯酚-1,3-噁唑/二氢咪唑-2-酮/硫酮化合物在制备尿素酶抑制剂中的应用。
7.根据权利要求6所述的应用，其特征在于所述尿素酶抑制剂为治疗胃肠道炎症、胃溃疡、胃癌、肾结石或肾盂肾炎的药物。
8.根据权利要求6所述的应用，其特征在于所述尿素酶抑制剂为尿素类肥料或动物饲料添加剂。
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