CN1149188C - 芳氨基亚甲基樟脑衍生物 - Google Patents
芳氨基亚甲基樟脑衍生物 Download PDFInfo
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- CN1149188C CN1149188C CNB981037909A CN98103790A CN1149188C CN 1149188 C CN1149188 C CN 1149188C CN B981037909 A CNB981037909 A CN B981037909A CN 98103790 A CN98103790 A CN 98103790A CN 1149188 C CN1149188 C CN 1149188C
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
- C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cosmetics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
式(1)的芳氨基亚甲基樟脑衍生物，式中C＝C双键是Z或E构型，而其中各变量具有以下的意义：R1为H、CH3，R2为H、C1～C6-烷基、C3～C8-环烷基、C2～C6-链烯基、C3～C8-环烯基、芳基或取代的芳基，R3为H、C1～C6-烷基、C3～C8-环烷基、芳基、取代的芳基、C1～C6-烷氧基、C1～C8-酰基，Ar为芳基、取代的芳基、杂芳基或取代的杂芳基，作为防晒剂的应用，特别是在化妆品和药物配方里的应用。
Description
本发明涉及式(1)的芳氨基亚甲基樟脑衍生物和它们作为防晒剂的应用，特别是在化妆品和药物配方中的应用：
以樟脑衍生物为主要成分的防晒剂是已知的。DE 2336219描述了在苯环的4位未取代的或由甲基、甲氧基或氯取代的磺化的亚苄基-和亚肉桂基樟脑衍生物。
DE 34 45 712描述了一些适于作为用于治疗皮肤病药物的未取代的樟脑衍生物，优选的是亚苄基樟脑衍生物。
DE 44 26 216描述了能够作为防晒剂和用于防止炎症和皮肤疾病的亚苄基降樟脑衍生物。
DE 44 24 489描述了用于制备取代的4-亚甲基肉桂酸衍生物的方法。
以插烯的酰胺类为主要成分的防晒剂同样是已知的。DE 33 16 287描述了一些有开链结构的并且适于在防晒剂组合物中作为滤光剂的插烯的酰胺。
要满足打算用来作为紫外线-A滤光剂的防晒剂的要求有很多(Sunscreens，ed.N.J.Lowe，N.A.Shaath，Marcel Dekker Inc.，NewYork 1990，230-231)。最主要的是：
1)在从320-360nm紫外线A区段有吸收最大值；
2)在该区段有高的吸收率；
3)无色，即大于400nm的吸收应该趋于0地小以便防止给皮肤保护制品着色或在使用后给衣物着色；
4)是光-和热稳定的；
5)与皮肤相容并且对皮肤不引起刺激或毒性作用；
6)很好地黏附到皮肤上；
7)与化妆物质相容并且易溶于化妆溶剂和组合物里；
8)是异构体纯的。
已知的亚肉桂基樟脑衍生物是广谱紫外线过滤吸收剂，在紫外线-A区段的保护作用不充分。此外，它们的溶解性，尤其是在油相里的溶解性对于某些应用是不令人满意的。
本发明的目的是提供一种适于作为紫外线-A滤光剂并且具有特别良好的光稳定性、在油相里溶解性良好的和在紫外线-A区段有令人满意的吸收极大值的化合物。
我们发现这个目的通过式(1)的芳氨基亚甲基樟脑衍生物以极好的方式达到了，
式中C＝C双键是Z或E构型，而
R1＝H、CH3，
R2＝H、C1～C6-烷基、C3～C8-环烷基、C2～C6-链烯基、C3～C8-环烯基、芳基或取代的芳基，
R3＝H、C1～C6-烷基、C3～C8-环烷基、芳基、取代的芳基、C1～C6-烷氧基、C1～C8-酰基，
Ar＝芳基、取代的芳基、杂芳基、取代的杂芳基。
在优选的式I化合物中，R1是CH3，R2＝R3＝H和Ar是2-(烷氧基羰基)苯基。
(1)是通过将式(2)的羟基亚甲基樟脑化合物(按照由L.Claisen，Ann.281，1894，306的描述制备)在一种碱或酸的存在下，在加入或不加入一种或几种溶剂及在0～200℃下与式(3)的胺类反应制备的。
(2)和(3)以等摩尔量反应制备根据本发明的化合物。
这个反应通常在例如甲醇或乙醇之类的质子溶剂(protic solvents)里进行的。不过，这个反也可以在醚中进行，例如二乙醚或四氢呋喃，在C1～C20石蜡混合物中或诸如己烷、甲苯或二甲苯的脂族或芳族溶剂里进行。
但这个反应也能够在没有溶剂的情况下进行。优选在低级醇里进行这个反应，以获得好的时空产率，只使用足量的溶剂用以产生在反应温度下可以搅拌的混合物。
(2)和(3)能够以任意的顺序进行反应。催化剂可以在最初就存在或者加入进去。这个反应也能够以一釜反应的形式进行。还可以将(2)首先与催化剂一起加入，再将(3)加入进去，或者相反。也可以将催化剂先与(3)一起加入而将(2)再加入进去。
反应能在0℃～+200℃下进行。优选的温度范围为20℃～100℃，最优选为60℃～90℃。
反应时间直接取决于温度。通常这个反应在特别优选的温度范围内在1～5小时之后完成。在更低的温度或更低的稳定状态浓度下，反应时间可能显著地增加而可能达到48小时。
能够使用的催化剂是任意的有机或无机碱或它们的混合物。典型的碱催化剂的例子是吡啶、三甲胺或无机碳酸盐。这些碱在混合物中可以呈均相或呈多相。
这个反应优选使用的催化剂是有机或无机酸或它们的混合物。可供使用的无机酸尤其可以是盐酸、硫酸、硝酸和/或磷酸。
可供使用的有机酸尤其可以是甲酸、乙酸、草酸、琥珀酸、抗坏血酸和/或诸如甲磺酸或甲苯磺酸之类的磺酸。
此外，酸离子交换剂同样也适于作为(2)与(3)反应的催化剂。
所要求的产品(1)采用常规的技术分离，例如沉积、过滤、离心法、相分离和溶剂萃取。
所要求的产品(1)可通过从有机溶剂和它们的混合物和/或水中再结晶来纯化。混合物优选含醇的。
纯化也可以通过区域熔融和色谱法以及蒸馏法进行。
本发明的化合物(1)可以含有樟脑部分(R1＝CH3)或降樟脑部分(R1＝H)。
R2有以下的意义：
H；C1～C6-烷基，优选C3-和C4-烷基，例如n-丙基、异丙基、n-丁基、异丁基、叔丁基；C3～C8-环烷基，优选环丙基、环丁基、环戊基、环己基；C2～C6-链烯基，优选乙烯基、丙烯基；C3～C8-环烯基，优选环戊烯基和环己烯基；芳基或取代的芳基，优选苯基、单或二取代的苯基、萘基或杂芳基，例如呋喃基、噻吩基或吡啶基。
R3有以下的意义：
H；C1～C6-烷基，优选C1～C4烷基，例如甲基、乙基、n-丙基、异丙基、n-丁基、异丁基、叔丁基；C3～C8-环烷基，优选环丙基、环丁基、环戊基、环己基；芳基或取代的芳基；优选苯基、单或二取代的苯基；C1～C6-烷氧基，优选甲氧基、乙氧基、n-丙氧基或异丙氧基；C1～C8-酰基，优选甲酰基、乙酰基、丙酰基、新戊酰基、n-丁酰基、异丁酰基、苯甲酰基。
Ar有以下的意义：
芳基，优选苯基、萘基；杂芳基，优选呋喃基、噻吩基、吡咯基或吡啶基；取代的芳基，优选单或二取代的苯基，取代的杂芳基，优选单或二取代的呋喃基、噻吩基、吡咯基或吡啶基，这里取代基可以是相同的或不同的，并且具有以下的意义：烷基、环烷基、烷氧基、氨基、烷氨基、羟基、卤素、酰基，特别优选酰氧基或酰氨基，和烷氧基羰基或氨基羰基、羧基、磺基或氨基磺酰基。
在本发明的式(1)的芳氨基亚甲基樟脑衍生物里的C＝C双键在合成之后既呈Z构型也呈E构型。结晶优先生成其中在C＝C双键上的取代基是在反位的式(1)的化合物。
本发明的化合物(1)以其高的光稳定性而著称并且特别适用于作为防晒剂，尤其是作为紫外线-A过滤吸收剂，特别是用于化妆品和药物应用。不过这种紫外线吸收作用也能够用于稳定塑料、染料配方或表面涂料。
化妆品或化妆组合物中化合物(1)的含量，除了在化妆品里常规的赋形剂和稀释剂之外，通常为配方(包含或不包含常规的化妆辅助剂)重量的0.1～15％，优选5～10％。
载体、辅助剂或稀释剂的性质决定了防晒剂最终制品是否为一种溶液、油、膏剂、软膏、洗剂、凝胶或粉剂。这一类型的组合物在例如Seifen，Oele，Fette，Wachse(1955)，147的杂志里有论述。
通常使用的和适于作为化妆辅助剂是，例如，诸如脂肪醇乙氧基化物、脱水山梨醇脂肪酸酯或羊毛脂衍生物之类的乳化剂，诸如羰基甲基纤维素或交联的聚丙烯酸之类的增稠剂，防腐剂和香味剂。
例如，防晒油以植物油为基，例如花生油、橄榄油、芝麻油、棉子油、椰子油、葡萄子油、蓖麻油，或以矿物油为基，例如液体矿脂或，尤其是液态石蜡、合成脂肪酸酯和甘油酯。软膏基质的例子为矿酯、羊毛脂、优赛林(eucerin)或聚乙二醇。
膏剂基质的例子为高脂肪乳油、甘油、聚糖和Tylose乳油，和以脂肪与鲸蜡醇蜡为基的乳油、羊毛脂乳油、可可油、蜂蜡、硬脂酸、十八烷醇、一硬脂酸甘油酯、天然或矿物油和脂。
乳液基质的例子为硬脂酰乙二醇，诸如杏仁油、液体石蜡和矿酯之类的植物油和/或矿物油和水的混合物，或乙醇、水、羊毛脂和黄蓍胶的混合物，或乙醇、硬脂精、水、黄蓍胶和甘油的混合物，或硬脂酸、液体石蜡、丙醇或异丙醇以及水的混合物。
本发明的化合物能够在适合的组合物里作为唯一的紫外线吸收剂使用；不过它们也可以与其它紫外线吸收剂特别是与紫外线-B吸收剂结合使用。
这类化合物的例子是p-氨基苯甲酸乙酯，p-甲氧基肉桂酸-2-乙基己基酯，2-氰基-3，3-二苯基丙烯酸-2-乙基己酯，2-苯基苯并咪唑磺酸和盐，2-羟基-4-甲氧基二苯酮，2-羟基-4-甲氧基二苯酮-5-磺酸，3-(4-甲基亚苄基)-d，l-樟脑，2，4，6-三(p-2-乙基己氧基羰基苯胺基)-1，3，5-三嗪。
以下通用的方法特别优选用于制备本发明的化合物(1)：
将等摩尔量(22mmol)的羟基亚甲基樟脑化合物(2)和胺(3)溶于20ml甲醇里，并且在加入0.1ml浓盐酸之后在65℃加热2小时。在反应混合物已经冷却至10℃之后，所要求的产品(1)结晶出来并且能够通过过滤、洗涤和随后的干燥分离出分析纯的所要求的产品(1)。
实施例1
采用通用的方法将4g(22mmol)羟基亚甲基樟脑与5.45g(22mmol)p-氨基苯甲酸乙基己酯反应以生成9g下式的化合物：
UV(CH3OH)：λmax＝358nm，E1 1＝1044
IR：υ＝3220，2959，1711，1692，1636，1602(s)，1587，1263(s)，1176，1105，1072cm-1.1H-NMR(CDCl3)：δ＝9.87(d，1H，J＝11.2Hz)，
7.95(d，2H，J＝7.6Hz)，
6.91(m，3H)，
4.16(d，2H，J＝8.2Hz)，
2.40(m，1H)，
2.01(m，1H)，
1.68(m，2H)，
1.32(m，10H)，
0.96(m，15H).
实施例2
采用通用的方法将4g(22mmol)羟基亚甲基樟脑与4.29g(22mmol)o-氨基苯甲酸丁基酯反应以生成4.9g下式的化合物：
UV(CH3OH)：λmax＝358nm，E1 1＝802IR：υ＝3274，2943，1687，1622(s)，1602，1592，1272，1246，1156cm-1.1H-NMR(CDCl3)：δ＝10.13(d，1H，J＝16.2Hz)，
7.98(d，1H，J＝6.9Hz)，
7.68(d，1H，J＝16.2Hz)，
7.49(t，1H，J＝7.2Hz)，
7.21(d，1H，J＝6.9Hz)，
6.87(d，1H，J＝7.2Hz)，
4.37(t，2H，J＝8.1Hz)，
2.81(m，1H)，
2.11(m，1H)，
1.4-1.6(m，9H)，
0.99(m，10H).
实施例3
在表1里的化合物3.1～3.15按照实施例1和2制备
表1
| 化合物 | R1 | R2 | R3 | Ar |
| 3.1 | CH3 | H | H | 4-CH3O-Ph |
| 3.2 | CH3 | H | H | 2，4-Di-CH3O-Ph |
| 3.3 | CH3 | CH3 | H | 4-CH3O-Ph |
| 3.4 | CH3 | CH3 | CH3 | 4-CH3O-Ph |
| 3.5 | H | H | H | 4-CH3O-Ph |
| 3.6 | CH3 | H | H | 2-(H2N-CO)-Ph |
| 3.7 | CH3 | H | H | 4-(H2N-CO)-Ph |
| 3.8 | H | H | H | 2-(CH3O-CO)-Ph |
| 3.9 | H | H | H | 4-(C8H17O-CO)-Ph |
| 3.10 | CH3 | H | H | 4-quinolinyl |
| 3.11 | CH3 | H | H | 2-CO2H-Ph |
| 3.12 | CH3 | H | H | 4-SO3H-Ph |
| 3.13 | CH3 | H | H | 4-SO2NH2-Ph |
| 3.14 | CH3 | CH3 | H | 2-CO2H-Ph |
| 3.15 | CH3 | CH3 | H | 2-(nC4H9O-CO)-Ph |
Claims (7)
1、一种保护皮肤免受紫外线辐射的方法，包括将包含式(1)的芳氨基亚甲基樟脑衍生物作为防晒剂的化妆品组合物施用于皮肤上
式中C＝C双键是Z或E构型，而其中各变量具有以下的意义：
R1 H、CH3，
R2 H、C1～C6-烷基、C3～C8-环烷基、C2～C6-链烯基、C3～C8-环烯基、苯基、单或二取代的苯基、萘基或呋喃基、噻吩基或吡啶基，
R3 H、C1～C6-烷基、C3～C8-环烷基、苯基、单或二取代的苯基、C1～C6-烷氧基、C1～C8-酰基，
Ar 苯基、萘基；呋喃基、噻吩基、吡咯基或吡啶基；单或二取代的苯基，单或二取代的呋喃基、噻吩基、吡咯基或吡啶基，这里取代基可以是相同的或不同的，并且具有以下的意义：烷基、环烷基、烷氧基、氨基、烷氨基、羟基、卤素、酰基、酰氧基或酰氨基、烷氧基羰基或氨基羰基、羧基、磺基或氨基磺酰基。
2、如权利要求1所述的方法，其中C＝C双键是E构型。
3、如权利要求1或2所述的方法，其中R1是CH3，R2＝R3＝H和Ar是2-(烷氧基羰基)苯基。
4、一种化妆品组合物，它包含如权利要求1的式(1)芳氨基亚甲基樟脑衍生物。
5、如权利要求4的化妆品组合物，它包含0.1-15％重量的式(1)芳氨基亚甲基樟脑衍生物。
6.式(1)的芳氨基亚甲基樟脑衍生物，其中R1是CH3，R2＝R3＝H和Ar是2-(烷氧基羰基)苯基。
7.如权利要求6的芳氨基亚甲基樟脑衍生物，其中C＝C双键是E构型。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19701448A DE19701448A1 (de) | 1997-01-17 | 1997-01-17 | Arylaminomethylencampherderivate |
| DE19701448.8 | 1997-01-17 |
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| Publication Number | Publication Date |
|---|---|
| CN1188758A CN1188758A (zh) | 1998-07-29 |
| CN1149188C true CN1149188C (zh) | 2004-05-12 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB981037909A Expired - Fee Related CN1149188C (zh) | 1997-01-17 | 1998-01-13 | 芳氨基亚甲基樟脑衍生物 |
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| Country | Link |
|---|---|
| US (1) | US5932195A (zh) |
| EP (1) | EP0854133B1 (zh) |
| JP (1) | JP4154018B2 (zh) |
| CN (1) | CN1149188C (zh) |
| AU (1) | AU748609B2 (zh) |
| DE (2) | DE19701448A1 (zh) |
| ES (1) | ES2179389T3 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2336219A1 (de) * | 1973-07-17 | 1975-02-20 | Merck Patent Gmbh | Campherderivate |
| US4663155A (en) * | 1982-05-05 | 1987-05-05 | Johnson & Johnson Baby Products Company | Sunscreen compositions |
| LU85144A1 (fr) * | 1983-12-16 | 1985-09-12 | Oreal | Derives insatures du camphre,leurs procedes de preparation et leur application dans le domaine therapeutique et cosmetique |
| DE4424489A1 (de) * | 1994-07-12 | 1996-01-18 | Merck Patent Gmbh | Verfahren zur Herstellung von substituierten 4-Methyliden-Zimtsäure-Derivaten |
| DE4426216A1 (de) * | 1994-07-23 | 1996-01-25 | Merck Patent Gmbh | Benzyliden-Norcampher-Derivate |
-
1997
- 1997-01-17 DE DE19701448A patent/DE19701448A1/de not_active Withdrawn
-
1998
- 1998-01-13 ES ES98100435T patent/ES2179389T3/es not_active Expired - Lifetime
- 1998-01-13 EP EP98100435A patent/EP0854133B1/de not_active Expired - Lifetime
- 1998-01-13 US US09/006,175 patent/US5932195A/en not_active Expired - Fee Related
- 1998-01-13 CN CNB981037909A patent/CN1149188C/zh not_active Expired - Fee Related
- 1998-01-13 DE DE59804542T patent/DE59804542D1/de not_active Expired - Lifetime
- 1998-01-14 JP JP00591898A patent/JP4154018B2/ja not_active Expired - Fee Related
- 1998-01-16 AU AU52109/98A patent/AU748609B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU5210998A (en) | 1998-07-23 |
| DE59804542D1 (de) | 2002-08-01 |
| EP0854133B1 (de) | 2002-06-26 |
| CN1188758A (zh) | 1998-07-29 |
| JPH10226671A (ja) | 1998-08-25 |
| EP0854133A1 (de) | 1998-07-22 |
| AU748609B2 (en) | 2002-06-06 |
| US5932195A (en) | 1999-08-03 |
| ES2179389T3 (es) | 2003-01-16 |
| DE19701448A1 (de) | 1998-07-23 |
| JP4154018B2 (ja) | 2008-09-24 |
| MX9800488A (es) | 1998-10-31 |
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