CN1101801C - (e)－2,3－二卤－2－丁烯－1,4－二醇及其衍生物的合成方法 - Google Patents
(e)－2,3－二卤－2－丁烯－1,4－二醇及其衍生物的合成方法 Download PDFInfo
- Publication number
- CN1101801C CN1101801C CN00114139A CN00114139A CN1101801C CN 1101801 C CN1101801 C CN 1101801C CN 00114139 A CN00114139 A CN 00114139A CN 00114139 A CN00114139 A CN 00114139A CN 1101801 C CN1101801 C CN 1101801C
- Authority
- CN
- China
- Prior art keywords
- alcohol
- glycol
- organic compound
- low polar
- mixed solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 21
- 230000002194 synthesizing effect Effects 0.000 title 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000002140 halogenating effect Effects 0.000 claims abstract description 11
- -1 copper halide Chemical class 0.000 claims abstract description 10
- 239000012046 mixed solvent Substances 0.000 claims abstract description 10
- 150000002894 organic compounds Chemical class 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 239000010949 copper Substances 0.000 claims abstract description 8
- 229910052802 copper Inorganic materials 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 2
- 150000004996 alkyl benzenes Chemical class 0.000 claims description 2
- 239000006227 byproduct Substances 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000002191 fatty alcohols Chemical class 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 4
- 230000026030 halogenation Effects 0.000 description 4
- 238000005658 halogenation reaction Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 229940045803 cuprous chloride Drugs 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910006024 SO2Cl2 Inorganic materials 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000004303 annulenes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属于一种立体专一制备(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物的新方法，采用醇与低极性有机化合物组成的混合溶剂为反应溶剂，在醇与低极性有机化合物体积配比为0.1～5∶10时，以α-炔醇或其衍生物为原料，以卤化铜CuX2(X＝Br，Cl)为卤化剂能制得立体专一的(E)构型产品，产率达100%，产品纯度达98%以上，而且反应时间短，条件温和、无污染。
Description
本发明是立体专一性合成(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物的新方法，其中卤原子为氯或溴。
(E)-2，3-二卤-2-丁烯-1，4-二醇是重要的医药、农药和香料及其大分子的合成中间体。例如：(E)-2，3-二氯-2-丁烯-1，4-二醇可作为合成大环轮烯的原料(John Anthony，CarolynB.Knobler；Angew.Chem.Int.Ed.Engl.1993，405-409)；(E)-2，3-二溴-2-丁烯-1，4-二醇可用来合成多种呋喃及其衍生物(Carlos Alvarez-Ibarra，Maria L.Quiroga，EmilioToledano；Tetrahedron，1996，52，4065-4078)等等。有关(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物的合成技术中主要有以下几种：(1)、用卤素直接卤化相应的炔醇(Uemura，S.，Okazaki，H.，Okano，M.，Sawada，S.，Okada，A.，Kuwabata，K.；Bull.Chem.Soc.Japan，1978，51，1911)；(2)、用三卤化硼(BX3)作为卤化剂来卤化相应的炔醇(JacquesBerthelot，Yamina Benammar，Bernard desmazières；Synthet ic Communications，1997，27，2685-2876)；(3)、用三卤四丁基铵(TBAX3)作为卤化剂来卤化相应的炔醇(JacquesBerthelot，Michel Fournier；Can.J.Chem.1986，64，603-607)；(4)、用磺酰氯(SO2Cl2)作为氯化剂来氯化相应的炔醇(Sakae Uemura，Chiaki Masaki，Akio Toshimitsu，SeijiSawada；Bull.Chem.Soc.Japan，1981，54，2843-2844)；(5)、用卤化铜作为卤化剂来卤化相应的炔醇(C.E.Castro，E.J.Gaughan，D，C.Cwsley；J.Org.Chem.1965，30，587-592；Sakae Uemura，Aki ra Onoe，Masaya Okano；J.C.S.Chem.Comm.1975，925-926)。
在上述方法中，其中方法(1)-(4)中使用的卤化剂刺激性强，对人体危害性大，而且所得产物复杂，而且所得的2，3-二卤-2-丁烯-1，4-二醇及其衍生物也都是(Z)和(E)构型的混合物。而方法(5)虽然对人体无损害，但在所报道的方法中采用了对人体毒害性大的甲醇为反应溶剂，所得的产物也同样复杂，其中用溴化铜溴化炔醇时所得的(E)-2，3-二溴-2-烯醇产率较低(31％)，用氯化铜氯化炔醇时所得产物不是(E)-2，3-二氯-2-烯醇，而是2，3，3-三氯-2-烯醇，而且反应须回流，所须卤化铜的量大(卤化铜/底物＝4∶1到6∶1左右)，在该文献中，无卤化炔二醇的报道。
本发明的目的是提供一种能立体专一性合成(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物的新方法。
本发明提供的合成(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物的方法是采用α-炔醇及其衍生物经过卤化反应得到(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物。该法还可通过简单处理得到卤化亚铜这一重要的化工原料，具体实施方案如下：
采用α-炔醇或其衍生物为原料，以卤化铜CuX2(X＝Br，Cl)为卤化剂进行卤化反应，反应于醇与低极性有机化合物组成的混合溶剂中进行，混合溶剂中醇为含1～6个碳原子的脂肪醇，低极性有机化合物为烷烃或芳烃有机溶剂，醇与低极性有机化合物的体积配比为0.1～5∶10；在室温下反应0.5～4小时后过滤，滤液经蒸馏后重结晶得纯净的产品。过滤后的固体经乙醚洗涤可得卤化亚铜(白色粉末)副产品。
本发明中的α-炔醇，尤其可以是丙炔醇、3-烷基丙炔醇、3-芳基丙炔醇、2-丁炔-1，4-二醇，3-己炔-2，5-二醇，2，5-二甲基-3-己炔-2，5-二醇、1，4-二芳基-2-丁炔-1，4-二醇，这些都是常用的合成原料；混合溶剂中所用低极性化合物为烷烃和芳烃有机溶剂，尤其以正己烷、正戊烷、苯或烷基苯反应效果为佳。
混合溶剂中优选的醇与低极性化合物的配比为0.1～1∶10。
所得产物的立体结构经红外光谱测定为立体专一的(E)构型，一般地，分子比较对称的烯烃如(E)-2，3-二氯-2-丁烯-1，4-二醇，在1680～1620cm-1通常观察不到双键的伸缩震动峰。
本发明提供的用卤化铜为卤化剂将α-炔醇制备(E)-二卤代烯醇新方法，反应时间短，反应条件温和，反应操作简单，产率达100％，产品纯度经GC测定也能达98％以上，反应溶剂可回收并且可重复使用。所需卤化铜用量少(计算量)，反应后转化为卤化亚铜，无卤原子流失，对环境无污染，同时卤化亚铜也是重要的化工原料。本发明所提供的方法与前人的方法最大区别在于溶剂的使用。前人的方法通常使用极性溶剂如甲醇，乙腈等，这样不但反应产物复杂，而且产物立体选择难以控制。而我们发明的方法采用较低极性的混合溶剂，不但产物单一，而且立体选择性也能达到专一。
实施例1
在25mL的圆底烧瓶中先加入10mL苯和0.6mL甲醇，然后加入2-丁炔-1，4-二醇(86mg，1mmol)、CuCl2(135mg，2mmol)。在室温下搅拌反应2小时后，反应完全，过滤，固体部分用乙醚(2×5mL)洗涤2次。固体即为氯化亚铜(白色粉末，99.5mg，2mmol)。蒸馏除去滤液后得粗产物，用CCl4重结晶得更为纯净的(E)-二氯代烯醇，所得产物为(E)-2，3-二氯-2-丁烯-1，4-二醇，产量为156mg，产率为100％，产品纯度达98％(GC)以上。
实施例2
在25mL的圆底烧瓶中先加入10mL甲苯和0.1mL丁醇，然后加入炔丙醇(56mg，1mmol)、CuCl2(135mg，2mmol)。在室温下搅拌反应4小时后，反应完全，过滤，固体部分用乙醚(2×5mL)洗涤2次。固体即为氯化亚铜(白色粉末，99.5mg，2mmol)。蒸馏除去滤液后得粗产物，分馏得更为纯净的(E)-二氯代烯醇，所得产物为(E)-2，3-二氯-2-丙烯-1-醇，产量为126mg，产率为100％，产品纯度达98％(GC)以上。
实施例3
在25mL的圆底烧瓶中先加入10mL苯和1mL丁醇，然后加入2-丁炔-1，4-二醇(86mg，1mmol)、CuBr2(224mg，2mmol)。在室温下搅拌反应0.5小时后，反应完全，过滤，固体部分用乙醚(2×5mL)洗涤2次。固体即为溴化亚铜(白色粉末，99.5mg，2mmol)。蒸馏除去滤液后得粗产物，用CCl4重结晶得更为纯净的(E)-二溴代烯醇，所得产物为(E)-2，3-二溴-2-丁烯-1，4-二醇，产量为246mg，产率为100％，产品纯度达98％(GC)以上。
Claims (5)
1、一种立体专一性合成(E)-2，3-二卤-2-丁烯-1，4-二醇及其衍生物的方法，采用α-炔醇或其衍生物为原料，以卤化铜CuX2为卤化剂进行卤化反应，其中X＝Br，Cl，其特征在于：反应于醇与低极性有机化合物组成的混合溶剂中进行，混合溶剂中醇为含1～6个碳原子的脂肪醇，低极性有机化合物为烷烃或芳烃有机溶剂，醇与低极性有机化合物的体积配比为0.1～5∶10；在室温下反应0.5～4小时后过滤，滤液经蒸馏后重结晶得纯净产品。
2、根据权利要求1所述的方法，其特征在于：α-炔醇为丙炔醇、3-烷基丙炔醇、3-芳基丙炔醇、2-丁炔-1，4-二醇，3-己炔-2，5-二醇，2，5-二甲基-3-己炔-2，5-二醇、1，4-二芳基-2-丁炔-1，4-二醇。
3、根据权利要求1所述的方法，其特征在于：混合溶剂中低极性有机化合物为正己烷、正戊烷、苯或烷基苯。
4、根据权利要求1所述的方法，其特征在于：混合溶剂中醇与低极性有机化合物的配比为0.1～1∶10。
5、根据权利要求1所述的方法，其特征在于：反应可得卤化亚铜副产品。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN00114139A CN1101801C (zh) | 2000-03-22 | 2000-03-22 | (e)－2,3－二卤－2－丁烯－1,4－二醇及其衍生物的合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN00114139A CN1101801C (zh) | 2000-03-22 | 2000-03-22 | (e)－2,3－二卤－2－丁烯－1,4－二醇及其衍生物的合成方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1271714A CN1271714A (zh) | 2000-11-01 |
| CN1101801C true CN1101801C (zh) | 2003-02-19 |
Family
ID=4583856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00114139A Expired - Fee Related CN1101801C (zh) | 2000-03-22 | 2000-03-22 | (e)－2,3－二卤－2－丁烯－1,4－二醇及其衍生物的合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1101801C (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109020783B (zh) * | 2018-07-18 | 2020-04-28 | 浙江师范大学 | 一种(e)-2,3-二溴-2-丁烯-1,4-二醇的制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3746726A (en) * | 1965-02-25 | 1973-07-17 | Basf Ag | Brominating butyne-(2)-diol-(1,4) |
-
2000
- 2000-03-22 CN CN00114139A patent/CN1101801C/zh not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3746726A (en) * | 1965-02-25 | 1973-07-17 | Basf Ag | Brominating butyne-(2)-diol-(1,4) |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1271714A (zh) | 2000-11-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yamamura et al. | The reaction of σ-vinylpalladium complexes with alkyllithiums. Stereospecific syntheses of olefins from vinyl halides and alkyllithiums | |
| CA1298309C (en) | Benzocycloheptene derivatives | |
| Danheiser et al. | Aromatic Annulation Strategy for the Synthesis of Angularly-Fused Diterpenoid Quinones. Total Synthesis of (+)-Neocryptotanshinone,(-)-Cryptotanshinone, Tanshinone IIA, and (.+-.)-Royleanone | |
| Snider et al. | Oxidative cyclization of. delta.,. epsilon.-and. epsilon.,. zeta.-unsaturated enol silyl ethers | |
| Hosomi et al. | Chemistry of organosilicon compounds—165: 2-Trimethylsilyl-methyl-1, 3-Butadiene—A versatile building block for terpene synthesis | |
| Schwaebe et al. | Nickel (0)-catalyzed coupling of vinylzirconiums to α-bromo-α, α-difluoro esters. Convenient generation of a functionalized allyldifluoro moiety | |
| CN1101801C (zh) | (e)－2,3－二卤－2－丁烯－1,4－二醇及其衍生物的合成方法 | |
| Wang et al. | A new and practical synthesis of vinyl dichlorides via a non-Wittig-type approach | |
| Krishna et al. | The use of acetylenic aldehydes in Baylis–Hillman reactions: synthesis of versatile allyl propargyl alcohols | |
| Tanaka et al. | Synthesis of aromatic compounds containing a 1, 1-dialkyl-2-trifluoromethyl group, a bioisostere of the tert-alkyl moiety | |
| Luo et al. | Palladium-catalyzed cyclization and cross-coupling of acetylenic aryl triflates with organotin reagents | |
| Wei et al. | Asymmetric synthesis of chiral β-iodo Baylis–Hillman esters using MgI2 as promoter via a one-pot three-component reaction | |
| CN101307009A (zh) | (土)4-氟-α-(2-甲基-1-氧丙基)-γ-氧代-N,β-二苯基苯丁酰胺的新合成方法 | |
| Hu et al. | Synthesis of trifluoromethyl-substituted conjugated enynes including a fluorinated siccayne | |
| Ishizaki et al. | Scope and limitation of intramolecular Pauson–Khand reaction of fluorine-containing enynes | |
| Zhang et al. | A kinetic separation method for the stereoselective preparation of (Z)-and (E)-monofluoroenynes from E/Z mixtures of 1-bromo-1-fluoroolefins | |
| Arai et al. | SN2'-Regio-and Diastereoselective Allylation of Organozinc Reagents. | |
| Shi et al. | 2-(Acetoxymethyl)-1, 1-difluoro-3-(trimethylsilyl) propene: Preparation and utility as a novel bifunctional reagent containing a CF2 group | |
| Deagostino et al. | α, β-Unsaturated Acetals in Synthesis | |
| Chang et al. | . alpha.-Isopropenylation of ketones. Use of an enol ether-iron complex as an isopropenyl cation equivalent | |
| Casy et al. | Alkylation reactions of propargyl alcohol; improved routes to prostaglandin α-side chain precursors | |
| Uno et al. | An efficient synthesis of perfluoroalkyl ketones using perfluoroalkyllithiums. | |
| Viala et al. | C3-homologation. Synthesis of C19-skipped polyenic pheromones. | |
| Cloux et al. | Pair-Wise Interactions by Gas Chromatography; Part III: 1, 2 Synthesis of Isosteric Stationary Phases for Gas Chromatography | |
| JPH05201881A (ja) | 環状化合物の転移方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |