TW201803846A - 適於特用化學品應用之羥基甲硫胺酸類似物調配物 - Google Patents
適於特用化學品應用之羥基甲硫胺酸類似物調配物 Download PDFInfo
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- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000021470 vitamin B5 (pantothenic acid) Nutrition 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000021467 vitamin B7(Biotin) Nutrition 0.000 description 1
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- 239000011727 vitamin B9 Substances 0.000 description 1
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- 239000011718 vitamin C Substances 0.000 description 1
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- 229940046009 vitamin E Drugs 0.000 description 1
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- 150000003751 zinc Chemical class 0.000 description 1
- 229940043810 zinc pyrithione Drugs 0.000 description 1
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- VYXPIEPOZNGSJX-UHFFFAOYSA-L zinc;dioxido-oxo-phenyl-$l^{5}-phosphane Chemical compound [Zn+2].[O-]P([O-])(=O)C1=CC=CC=C1 VYXPIEPOZNGSJX-UHFFFAOYSA-L 0.000 description 1
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Abstract
本發明係關於包含羥基甲硫胺酸類似物且具有低含量之硫酸根離子及硫酸氫鹽之調配物、製備該等調配物之方法、包含該等調配物之組合物及使用該等調配物之方法。
Description
本發明概言之係關於具有低含量之硫酸根及硫酸氫根離子及改良之色彩及氣味之羥基甲硫胺酸類似物調配物。因此,該等調配物適於特用化學品應用。
羥基甲硫胺酸類似物(例如2-羥基-4-(甲硫基)丁酸(HMTBA))廣泛用作牲畜之飼料添加劑。HMTBA通常製造為具有硫磺氣味之深色液體,其含有至少約88% HMTBA游離酸,至多約12%水及約0.5-3%之硫酸氫銨,以及其他微量雜質。HMTBA之化學功能使其在另外多種應用中成為多種材料之適宜構建單元,且業內最近對於使用HMTBA用於特用化學品(例如聚合物、表面活性劑、溶劑等)再次產生關注。所有該等特用應用皆需要關於最終產品之色彩、氣味、儲放壽命且由此關於作為組分或原材料之HMTBA之明確規定。雖然硫酸氫銨係飼料中之已知抗細菌劑或酸化劑,但其促成特用化學品應用中不期望之色彩及氣味產生。因此,業內需要具有用於特用化學品用途之最少色彩及氣味之熱穩定HMTBA調配物。
在本揭示內容之各個態樣中提供調配物,其包含式(I)化合物、以重量計約15%或更少之水及以重量計少於約2700 ppm之硫酸根離子,其中在少於85%之式(I)化合物中k為1:其中: R1
係烷基或經取代之烷基; k係1至1000之整數;且 n係1至20之整數。 本揭示內容之另一態樣涵蓋調配物,其包含式(I)化合物、以重量計約15%或更少之水,且具有200或更小之美國公共衛生協會(American Public Health Association,APHA)色彩值,其中在少於85%之式(I)化合物中k為1:式(I)化合物:其中: R1
係烷基或經取代之烷基; k係1至1000之整數;且 n係1至20之整數。 本揭示內容之另一態樣提供自包含式(I)化合物、硫酸根離子、硫酸氫根離子及發色體之飼料級調配物製備上文所闡述之調配物之方法。該方法包含(a) 使包含式(I)化合物之飼料級調配物之水溶液與吸附劑接觸以去除發色體,藉此產生經脫色之水溶液;(b) 用具有有限水可混溶性之溶劑萃取該經脫色之水溶液以形成包含該具有有限水可混溶性之溶劑及式(I)化合物之有機相及包含硫酸根離子及硫酸氫鹽之水相;及(c) 自該有機相去除該溶劑以形成調配物。 本揭示內容之另一態樣涵蓋自包含式(I)化合物、硫酸根離子、硫酸氫根離子及發色體之飼料級調配物製備上文所闡述之調配物之方法。該方法包含(a) 使包含式(I)化合物之飼料級調配物之水溶液與吸附劑接觸以去除發色體,藉此產生經脫色之水溶液;(b) 使該經脫色之水溶液與至少一種離子交換樹脂接觸以去除硫酸根離子及硫酸氫鹽並形成水性析出液;及(c) 自該水性析出液去除水以形成調配物。 下文更詳細地闡述本發明之其他特徵及迭代。
本揭示內容提供具有低含量之硫酸根離子、硫酸氫根離子及發色體之羥基甲硫胺酸類似物之調配物。由於硫酸根及硫酸氫根離子之含量較低,因此本文中所揭示調配物在升高溫度下化學穩定。即,其不會變成有色或有氣味的。因此,本文中所揭示之羥基甲硫胺酸類似物調配物適於特用化學品應用。亦提供製備本文中所揭示調配物之方法,其中該等方法包含自甲硫胺酸類似物之飼料級羥基調配物去除硫酸根離子、硫酸氫根離子及發色體。本文中亦提供包含本文中所揭示調配物之組合物,以及使用本文中所揭示調配物作為起始材料製備羥基甲硫胺酸類似物之衍生物之方法。(I) 調配物
本揭示內容之一個態樣提供具有低含量之硫酸根離子、硫酸氫根離子及發色體之羥基甲硫胺酸類似物調配物,使得該等調配物適於特用化學品應用。具體而言,本文中所揭示調配物包含式(I)化合物(如下文所詳述)、以重量計約15%或更少之水、以重量計約2700 ppm或更少之硫酸根離子、以重量計約500 ppm或更少之硫酸氫根離子,且在15%水含量下pH為至少1.3。因此,該等調配物實質上不含發色體及揮發性有氣味之化合物。此外,該等調配物在升高溫度下穩定。(a) 調配物之組分 (i) 式 (I) 化合物
本文中所揭示調配物包含式(I)化合物:其中: R1
係烷基或經取代之烷基; k係1或更大之整數;且 n係1或更大之整數。 在一些實施例中,R1
可係C1
至C6
烷基或C1
至C6
經取代之烷基。在其他實施例中,R1
可係甲基、乙基、丙基、異丙基、丁基、第三丁基、己基、環己基及諸如此類。在具體實施例中,R1
可係甲基。 在某些實施例中,n可在1至20或1至10範圍內。在其他實施例中,n可係1、2、3、4或5。在具體實施例中,n可係1或2。 一般而言,k可在1至約1000範圍內。舉例而言,k可在1至約500、1至約250、1至約100、1至約50、1至約20、1至約10、1至5、1至4或1至3範圍內。在一些實施例中,k在調配物之每種化合物中可係相同的(例如,k可係1,k可係2等)。在其他實施例中,k在調配物之各化合物之間可不同(例如,k可係1-4、1-10、1-20等)。換言之,調配物包含單體、二聚體、三聚體、四聚體及更長寡聚物之混合物。 在一些實施例中,調配物中單體(即,k = 1)之百分比可有所變化。舉例而言,單體之百分比以重量計可係約99.9%或更少、可係約99%或更少、可係約95%或更少、可係約90%或更少、可係約85%或更少、可係約80%或更少、可係約75%或更少、可係約70%或更少、可係約60%或更少、可係約50%或更少、可係約40%或更少、可係約30%或更少、可係約20%或更少、可係約10%或更少或可係約5%或更少。在具體實施例中,單體之百分比以重量計可係約85%或更少。 在具體實施例中,R1
可係甲基且n可係2。 式(I)化合物可具有至少一個手性中心,如在以下示意圖中以星號所表示:其中R1
、k及n係如上文所定義。每一手性中心可具有R
或S
構型。在包含一個手性碳之化合物中,構型可係R
或S
。在包含兩個或更多個手性碳之化合物中,每一者之構型將獨立地係R
或S
。舉例而言,在包含兩個手性碳之化合物中,構型可係RR
、RS
、SR
或SS
,在包含三個手性碳之化合物中,構型可係RRR
、RRS
、RSR
、RSS
、SRR
、SRS
、SSR
或SSS
等。 調配物中式(I)化合物之濃度可端視且將端視(例如)調配物中水之濃度而變化。在各個實施例中,調配物包含以重量計至少約50%、至少約55%、至少約60%、至少約65%、至少約70%、至少約75%、至少約80%、至少約85%、至少約90%、至少約92%、至少約95%、至少約96%、至少約97%、至少約98%、至少約99%、至少約99.5%或至少約99.9%之式(I)化合物。 (ii) 水
調配物之另一組分係水。一般而言,調配物中所存在之水之量以重量計係約15%或更少。在一些實施例中,調配物包含以重量計約10%或更少之水。在其他實施例中,調配物包含以重量計約5%或更少之水。在其他實施例中,調配物包含以重量計約4%或更少、約3%或更少、約2%或更少、約1%或更少之水。在一些實施例中,調配物之水含量可係以重量計約15%。在其他實施例中,調配物之水含量可係以重量計約5%。 (iii) 硫酸根離子
調配物亦包含硫酸根離子,其源自式(I)化合物之製造中所使用之硫酸。一般而言,調配物包含以重量計約2700 ppm或更少之硫酸根離子。在某些實施例中,調配物包含以重量計約2500 ppm或更少、約2000 ppm或更少、約1500 ppm或更少、約1000 ppm或更少、約500 ppm或更少、約100 ppm或更少、約50 ppm或更少或約10 ppm或更少之硫酸根離子。在一些實施例中,調配物包含以重量計至少1 ppm之硫酸根離子。舉例而言,調配物可包含以重量計1至約2700 ppm、1至約2000 ppm、1至約1500 ppm、1至約1000 ppm或1至約500 ppm之硫酸根離子。 (iv) 硫酸氫根離子
調配物亦包含硫酸氫根(HSO4 -
)離子,其可源自製造方法中所使用之硫酸氫銨。一般而言,調配物包含以重量計約500 ppm或更少之硫酸氫根離子。在各個實施例中,調配物包含以重量計約400 ppm或更少、約300 ppm或更少、約200 ppm或更少、約100 ppm或更少、約50 ppm或更少或約10 ppm或更少之硫酸氫根離子。在某些實施例中,調配物包含以重量計至少1 ppm之硫酸氫根離子。舉例而言,調配物可包含以重量計1至約500 ppm、1至約200 ppm之硫酸氫根離子。 (v) 例示性調配物
在一個實施例中,調配物包含式(I)化合物,其中R1
係甲基,n係2,且k ≥ 1,且調配物進一步包含以重量計約15%或更少之水、以重量計約2700 ppm或更少之硫酸根離子、以重量計約500 ppm或更少之硫酸氫根離子,且在15%之水含量下pH為至少1.3。(b) 調配物之性質
上文所詳述之調配物包含低含量之硫酸根及硫酸氫根離子。因此,在15%水含量下調配物之pH值為至少1.3。在某些實施例中,在15%之水含量下調配物之pH可在約1.3至約1.4、約1.4至約1.5、約1.5至約1.6、1.6至約1.7、約1.7至約1.8或大於約1.8範圍內。 由於硫酸根及硫酸氫根離子之含量較低,因此本文中所闡述之調配物在儲存條件下維持最低色彩,且在<140℃之溫度下反應少於12小時時不會賦予產品深色。換言之,調配物具有低含量之發色體或有色雜質。調配物之色彩可使用分光光度色度儀來量測並使用標準色度轉化為色彩值。在一些實施例中,色度可係美國公共衛生協會(APHA)色度,其亦稱為「黃度指數」。APHA色度範圍為0 (蒸餾水)至500 (淺黃色),且用於區分近「水白色」液體中之少量黃度。在其他實施例中,色度可係加德納(Gardner)色度。加德納色度範圍為0 (蒸餾水)至1 (淡黃色),然後繼續至暗黑18。在0至18範圍內,黃度增加且明度降低。 一般而言,本文中所揭示調配物之APHA色彩值為200或更小。在一些實施例中,在0.5-3%之水含量下APHA色彩值可係約150或更小、約100或更小或約50或更小。相比之下,式(I)化合物之飼料級調配物(例如,HMTBA動物補充劑)之APHA色彩值一般超出標度(即,>500)。 由於硫酸根離子及硫酸氫鹽之含量較低,因此本文中所闡述之調配物具有與特用應用相容之熱穩定性。在一些實施例中,本文中所揭示調配物可加熱至約140℃之溫度持續多達約12小時,而APHA色彩值無明顯變化。在其他實施例中,本文中所揭示調配物在加熱至約140℃持續多達約12小時之後,可具有300或更小之APHA色彩值。在其他實施例中,本文中所揭示調配物在加熱至約140℃持續多達約12小時之後可具有400或更小之APHA色彩值。在其他實施例中,本文中所揭示調配物在加熱至約140℃持續多達約12小時之後可具有500或更小之APHA色彩值。 本文中所揭示調配物亦具有低含量之有氣味化合物。一般而言,存在於調配物中之有氣味化合物係含硫化合物,例如甲基硫醇、二甲硫、烯丙基甲硫醚及二甲基二硫化物。有氣味化合物之含量可係以重量計約10 ppm或更小或約5 ppm或更小。 (II) 製備特用調配物之方法
本揭示內容之另一態樣涵蓋製備上文部分(I)中所闡述之特用調配物之方法。具體而言,本文中所揭示調配物係自包含式(I)化合物之飼料級調配物製備,其中該等飼料級調配物進一步包含硫酸根離子、硫酸氫根離子及發色體。一般而言,飼料級調配物包含以重量計約88%之式(I)化合物及以重量計約12%之水。一種方法包含藉由與吸收劑接觸自包含式(I)化合物之飼料級調配物之水溶液去除發色體,且然後藉由溶劑萃取去除硫酸根及硫酸氫根離子。另一方法包含藉由與吸收劑接觸自包含式(I)化合物之飼料級調配物之水溶液去除發色體,且然後藉由離子交換去除硫酸根及硫酸氫根離子。熟習此項技術者容易地瞭解可修改製程中之操作順序。(a) 溶劑萃取方法
一種製備本文中所揭示調配物之方法包含使包含式(I)化合物之飼料級調配物之水溶液與吸收劑接觸以去除發色體,藉此產生經脫色之水溶液。該方法進一步包含用具有有限水可混溶性之溶劑萃取該經脫色之水溶液使得形成兩相,有機相包含該溶劑及式(I)化合物且水相包含硫酸根及硫酸氫根離子。該方法之最後一步包含自該有機相去除該溶劑以製備部分(I)中所詳述之調配物。 (i) 飼料級調配物之水溶液
包含式(I)化合物之飼料級調配物亦包含硫酸根離子、硫酸氫根離子及發色體。包含式(I)化合物之飼料級調配物之水溶液可藉由用水稀釋飼料級調配物來製備。飼料級組合物亦可用水及極性溶劑之混合物稀釋以形成包含式(I)化合物之飼料級調配物之水溶液。欲與水混合之適宜極性溶劑之實例包括(但不限於)乙醯胺、乙酸、丙酮、乙腈、二甲基乙醯胺、二甲基甲醯胺、二甲亞碸、二噁烷、乙醇、甲醯胺、甲酸、甲醇、正丙醇、異丙醇、丙二醇、四氫呋喃或其組合。水及極性溶劑之混合物中所存在之極性溶劑之量可在以重量計約1%至約99%範圍內。 用於製備包含式(I)化合物之飼料級調配物之水溶液之水(或水及極性溶劑之混合物)之量可端視且將端視(例如)飼料級調配物中式(I)化合物之濃度而變化。一般而言,包含式(I)化合物之飼料級調配物經足夠水(或水及極性溶劑之混合物)稀釋,使得飼料級調配物之水溶液包含以重量計約18%或更少之式(I)化合物。在具體實施例中,飼料級調配物經足夠水(或水及極性溶劑之混合物)稀釋,使得飼料級調配物之水溶液包含以重量計約15%之式(I)化合物。 (ii) 可選過濾步驟
在一些實施例中,包含式(I)化合物之飼料級調配物之水溶液可經過濾以去除油性發色體。過濾可包含使包含式(I)化合物之飼料級調配物之水溶液通過矽藻土(diatomaceous earth,可以商標名CELITE®
獲得)、矽藻土(diatomite)、珍珠岩、二氧化矽、纖維素(例如,α-纖維素)或業內已知之其他助濾劑。 包含式(I)化合物之飼料級調配物之水溶液可在該水溶液製備之後立即過濾。或者,包含式(I)化合物之飼料級調配物之水溶液可在該水溶液製備之後一段時期過濾。舉例而言,在一些實施例中,包含式(I)化合物之飼料級調配物之水溶液可容許靜置多達約12小時且然後過濾。在其他實施例中,包含式(I)化合物之飼料級調配物之水溶液可容許靜置約12至18小時、約18至24小時或約24至30小時且然後過濾。 (iii) 與吸附劑接觸
製程包含使包含式(I)化合物之水溶液與吸附劑接觸以自該水溶液去除水性發色體,藉此產生經脫色之水溶液。 該製程中可使用各種吸附劑。適宜吸附劑之非限制性實例包括活性木炭(亦稱為活性碳)、矽膠、矽酸鹽、氧化鋁、沸石、膨潤土及礦物黏土。在具體實施例中,吸附劑係活性木炭。活性碳係具有極大內表面面積及孔體積且對於水具有較低親和力之非晶形固體。活性木炭可係粉末狀(或細粉狀)或顆粒狀(例如,4-10篩孔大小、20-40篩孔大小等)。 與包含式(I)化合物之水溶液接觸之吸附劑之量可變化且將有所變化。通常,吸附劑對式(I)化合物之重量比可在約0.001:1至約0.05:1範圍內。在其中吸附劑係活性木炭之實施例中,活性木炭對式(I)化合物之重量比可在約0.005:1至約0.01:1範圍內。 在一些實施例中,吸附劑與包含式(I)化合物之水溶液之間之接觸可使用分批製程來實施。舉例而言,可將吸附劑添加至包含式(I)化合物之水溶液並可藉由攪拌、振盪或其他形式之攪動來促進接觸。吸附劑與包含式(I)化合物之水溶液之間之接觸的持續時間可在約30分鐘至約48小時範圍內。適當時期之後,可藉由過濾、離心或其他適宜方式將吸附劑自經脫色之水溶液分離。在其他實施例中,吸附劑與包含式(I)化合物之水溶液之間之接觸可經由固定床(管柱)製程進行。舉例而言,包含式(I)化合物之水溶液可通過含有吸附劑之管柱,其中發色體吸附至吸附劑且流過管柱的係經脫色之水溶液。溶液可一次或經一次以上通過管柱。 包含式(I)化合物之飼料級調配物之水溶液與吸附劑之間之接觸可在約20-25℃(即,室溫)下進行。或者,接觸可在約25-30℃、約30-35℃或約35-40℃之溫度下進行。一般而言,吸附劑與包含式(I)化合物之飼料級調配物之水溶液之間之接觸在大氣壓下進行。 吸附劑自包含式(I)化合物之水溶液去除發色體,藉此產生包含式(I)化合物之經脫色之水溶液。經脫色之水溶液之APHA色彩值相對於包含式(I)化合物之飼料級調配物之起始水溶液可降低至少約2倍、至少約5倍、至少約10倍、至少約30倍或至少約60倍。 (iv) 溶劑萃取
製程進一步包含使包含式(I)化合物之經脫色之水溶液與具有有限水可混溶性之溶劑接觸以形成兩相,有機相包含該具有有限水可混溶性之溶劑及式(I)化合物,且水相包含硫酸根及硫酸氫根離子。 該製程中可使用各種溶劑。一般而言,具有有限水可混溶性之溶劑之水溶性為約10% w/w或更小。具有有限水可混溶性之溶劑之非限制性實例包括苯、正丁醇、乙酸丁酯、四氯化碳、氯苯、氯仿、氯甲烷、環己烷、二氯甲烷、1,2-二氯乙烷、二-第三丁基醚、二甲醚、二乙二醇、胺基甲酸二乙基酯、二乙醚、二甘二甲醚、二異丙基醚、乙酸乙酯、乙基第三丁基醚、環氧乙烷、氟苯、庚烷、己烷、甲基異丁基酮、甲基第三丁基醚、戊烷、三氯乙烯、甲苯、二甲苯或其組合。在一些實施例中,具有有限水可混溶性之溶劑可係甲基異丁基酮、乙酸乙酯或甲基第三丁基醚。 與包含式(I)化合物之經脫色之水溶液接觸之溶劑之量可端視且將端視所用溶劑及經脫色之水溶液中雜質之含量而變化。一般而言,溶劑對式(I)化合物之重量比可在約0.1:1至約15:1範圍內。在各個實施例中,溶劑對式(I)化合物之重量比可在約0.05:1至約10:1、約0.1:1至約5:1、約0.375:1至約1.5:1或約0.6:1至約0.9:1範圍內。 經脫色之水溶液與有限水可混溶溶劑之間之接觸形成兩相系統。可使用液體-液體萃取設備(例如Karr或Scheibel塔、混合器沉降器或業內已知之其他適宜連續接觸設備)來完成兩相接觸。可藉由反轉、旋轉、攪拌、振盪或業內已知之其他方式混合兩相系統來完成分批接觸。接觸後,使系統分離為兩相,即,有機相包含溶劑及式(I)化合物,且水相包含硫酸根及硫酸氫根離子。可使用工業分離器、離心分離器、傾析或業內已知之相似方式將兩相分離。 溶劑萃取可在約15℃至約80℃之溫度範圍內進行。在具體實施例中,溶劑萃取可在室溫下進行。 (v) 自有機相去除溶劑
製程進一步包含自有機相去除溶劑以形成上文部分(I)中所詳述之調配物。可藉由蒸發或蒸餾自有機相去除溶劑。適宜蒸發方式包括減壓蒸發、簡單效應蒸發、多效蒸發或其他蒸發方式。(b) 離子交換方法
製備本文中所揭示調配物之另一方法包含使包含式(I)化合物之飼料級調配物之水溶液與吸附劑接觸以去除發色體,藉此產生經脫色之水溶液。該方法進一步包含使該經脫色之水溶液與至少一種離子交換樹脂接觸以形成具有低含量之硫酸根及硫酸氫根離子之水性析出液。該方法之最後一步包含自該水性析出液去除水以形成上文部分(I)中所詳述之調配物。 (i) 與吸附劑接觸
製程包含使包含式(I)化合物之飼料級調配物之水溶液與吸附劑接觸以產生經脫色之水溶液。包含式(I)化合物之飼料級調配物之水溶液闡述於上文部分(II)(a)(i)中,可選過濾步驟闡述於上文部分(II)(a)(ii)中,且與吸附劑之接觸詳細闡述於上文部分(II)(a)(iii)中。 (ii) 與離子交換樹脂接觸
製程之下一步驟包含使經脫色之水溶液與至少一種離子交換樹脂接觸,藉此形成具有低含量之硫酸根及硫酸氫根離子之水性析出液。 大多數離子交換樹脂係基於交聯聚苯乙烯或經修飾含有官能基之交聯丙烯酸或甲基丙烯酸聚合物。在一些實施例中,離子交換樹脂可係陽離子交換樹脂。陽離子交換樹脂可為強酸性且含有磺酸官能基,或為弱酸性且含有羧酸官能基。在其他實施例中,離子交換樹脂可係陰離子交換樹脂。陰離子交換樹脂可為強鹼性且含有四級胺基官能基,或為弱鹼性且含有一級、二級及/或三級胺基官能基。 一般而言,製程包含與陽離子交換樹脂及陰離子交換樹脂二者接觸。陽離子交換樹脂自經脫色之水溶液去除銨及其他陽離子,且陰離子交換樹脂去除硫酸根、硫酸氫根及其他陰離子。在一些實施例中,製程包含與陽離子交換樹脂接觸,之後與陰離子交換樹脂接觸以形成水性析出液。在其他實施例中,製程包含與陰離子交換樹脂接觸,之後與陽離子交換樹脂接觸以形成水性析出液。 與經脫色之水溶液接觸之離子交換樹脂之量可端視且將端視(例如)樹脂上官能基之類型及經脫色之水溶液中鹽雜質之含量而變化。確定適當量之方式為業內所熟知。 (iii) 自水性析出液去除水
製程進一步包含自水性析出液去除水以形成上文部分(I)中所詳述之調配物。水(或水及極性溶劑之混合物)可藉由蒸發或蒸餾自水性析出液去除。適宜蒸發方式包括減壓蒸發、簡單效應蒸發、多效蒸發或其他蒸發方式。 (III) 包含特用調配物之組合物
本揭示內容之另一態樣涵蓋組合物,其包含含有式(I)化合物之特用調配物,其中該等組合物在各種應用中具有效用。舉例而言,包含本文中所揭示調配物之組合物可具有營養用途(例如,食品/飼料組合物、膳食補充劑及諸如此類)、工業用途(例如,蝕刻劑、電子化學品、聚合物、薄膜塗層等)或農業用途(例如,農用化學品調配物及諸如此類)。組合物可係固體(例如,粉末狀、顆粒狀、粒化、成型、固體基質、層狀、包封化等)或液體(其包括乳液)。(a) 營養組合物
在一些實施例中,組合物可具有營養或膳食用途。適宜營養組合物之實例包括(但不限於)食品組合物、營養補充劑、膳食補充劑、飼料組合物、飼料預混料、寵物食品、寵物食品補充劑、貓尿路保健食品及諸如此類。因此,營養組合物包含含有式(I)化合物之特用調配物及至少一種選自以下之試劑:營養劑、生物活性劑、賦形劑或其組合。 (i) 營養劑
營養劑提供卡路里且包括碳水化合物源、蛋白質源、脂肪源或其組合。 在一些實施例中,營養劑可包含至少一種碳水化合物源。碳水化合物源可係植物、微生物或動物來源。碳水化合物之適宜植物源之實例包括(但不限於)穀物,例如小麥、燕麥、稻穀、黑麥等;豆類,例如大豆、豌豆、黃豆及諸如此類;玉米;草;馬鈴薯;蔬菜植物;及植物果實。碳水化合物可係單醣,例如戊醣、葡萄糖、半乳糖等;二醣,例如蔗糖、乳糖、麥芽糖及諸如此類;寡醣,例如果寡醣、半乳寡醣、甘露寡醣等;或多醣,例如澱粉、肝醣、纖維素、阿拉伯糖木聚糖、果膠、樹膠、幾丁質等。 在其他實施例中,營養劑可包含至少一種蛋白質源。蛋白質源可源自植物。提供良好蛋白質源之適宜植物之非限制性實例包括莧菜、竹芋、大麥、蕎麥、芥花、木薯、鱧屬(channa)(鷹嘴豆)、豆科植物、扁豆、羽扇豆、玉蜀黍、粟、燕麥、豌豆、馬鈴薯、稻穀、黑麥、高粱、大豆、向日葵、木薯澱粉、黑小麥、小麥、海草及海藻。或者,蛋白質源可源自動物。舉例而言,動物蛋白質源可源自乳製品、鳥蛋或來自基於陸地或水生動物之肌肉、器官、結締組織或骨骼。 在其他實施例中,營養劑可包含至少一種脂肪源。脂肪源可係植物、動物或微生物來源。植物源脂肪之非限制性實例包括植物油(例如,芥花油、玉米油、棉籽油、棕櫚油、花生油、紅花油、大豆油及葵花油)及油籽(例如,芥花籽、棉籽、亞麻籽、亞麻仁、黑芝麻、芝麻籽、大豆及向日葵籽)、酒糟或海藻。動物源脂肪包括(但不限於)魚油(例如,鯡魚油、鯷魚油、長鰭金槍魚油、鱈魚肝油、青魚油、湖紅點鮭油、鯖魚油、鮭魚油及沙丁魚油)、高脂肪魚粉(例如,鯡魚粉、鯷魚粉、青魚粉、鱈魚粉、鮭魚粉、金槍魚粉及白魚粉)及動物脂肪(例如,家禽脂肪、牛油、黃油、豬油及鯨脂)。 (ii) 生物活性劑
適宜生物活性劑之實例包括維生素、礦物質、胺基酸或胺基酸類似物、抗氧化劑、有機酸、聚不飽和脂肪酸、精油、酶、益菌生(prebiotics)、益生菌、藥草、顏料、醫藥活性劑或其組合。 在一些實施例中,生物活性劑可係一或多種維生素。適宜維生素包括維生素A、維生素B1 (硫胺素)、維生素B2 (核黃素)、維生素B3 (菸鹼酸)、維生素B5 (泛酸)、維生素B6 (吡哆醇)、維生素B7 (生物素)、維生素B9 (葉酸)、維生素B12、維生素C、維生素D、維生素E、維生素K、其他B複合維生素(例如,膽鹼、肉鹼、腺嘌呤)或其組合。維生素之形式可包括維生素之鹽、維生素之衍生物、具有相同或相似維生素活性之化合物及維生素之代謝物。 在其他實施例中,生物活性劑可係一或多種礦物質。適宜礦物質之實例包括鈣、鉻、鈷、銅、碘、鐵、鎂、錳、鉬、硒、鋅或其組合。礦物質可係無機礦物質。適宜無機礦物質包括(例如)金屬硫酸鹽、金屬氧化物、金屬氫氧化物、金屬氯氧化物、金屬碳酸鹽及金屬鹵化物。或者,礦物質可係有機礦物質,例如包含金屬離子及有機配體之金屬螯合物。有機配體可係胺基酸、胺基酸類似物、蛋白質鹽或有機酸。 在其他實施例中,生物活性劑可係一或多種胺基酸。非限制性適宜胺基酸包括標準胺基酸(即,丙胺酸、精胺酸、天冬醯胺、天冬胺酸、半胱胺酸、麩醯胺酸、麩胺酸、甘胺酸、組胺酸、異白胺酸、白胺酸、離胺酸、甲硫胺酸、苯丙胺酸、脯胺酸、絲胺酸、蘇胺酸、色胺酸、酪胺酸及纈胺酸)、非標準胺基酸(例如,L-DOPA、GABA、2-胺基丁酸及諸如此類)、胺基酸類似物或其組合。胺基酸類似物包括α-羥基類似物,以及側鏈保護類似物或N-衍生胺基酸。 在替代實施例中,生物活性劑可係一或多種抗氧化劑。適宜抗氧化劑包括(但不限於)抗壞血酸及其鹽、棕櫚酸抗壞血酸酯、硬脂酸抗壞血酸酯、阿諾克索莫(anoxomer)、n-乙醯基半胱胺酸、異硫氰酸苄基酯、間胺基苯甲酸、鄰胺基苯甲酸、對胺基苯甲酸(PABA)、丁基羥基茴香醚(BHA)、二丁基羥基甲苯(BHT)、咖啡酸、角黃素、α-胡蘿蔔素、β-胡蘿蔔素、β-胡蘿蔔素、β-阿樸-胡蘿蔔素酸(beta-apo-carotenoic acid)、鼠尾草醇、香芹酚、兒茶酚、沒食子酸十六烷基酯、綠原酸、檸檬酸及其鹽、丁香提取物、咖啡豆提取物、對香豆酸、3,4-二羥基苯甲酸、N,N’-二苯基-對苯二胺(DPPD)、硫代二丙酸二月桂基酯、硫代二丙酸二硬脂醯基酯、2,6-二-第三丁基酚、沒食子酸十二烷基酯、依地酸(edetic acid)、鞣花酸、異抗壞血酸、異抗壞血酸鈉、七葉樹素、七葉苷、6-乙氧基-1,2-二氫-2,2,4-三甲基喹啉(乙氧基喹啉)、沒食子酸乙基酯、乙基麥芽酚、乙二胺四乙酸(EDTA)、桉樹提取物、丁香酚、阿魏酸、類黃酮(例如,兒茶素、表兒茶素、表兒茶素沒食子酸酯、表沒食子兒茶素(EGC)、表沒食子兒茶素沒食子酸酯(EGCG)、多酚表沒食子兒茶素-3-沒食子酸酯、黃酮(例如,芹菜配質、金黃酮、葉黃酮)、黃酮醇(例如,橡精、楊梅黃酮、山茶酚(daemfero))、黃烷酮、涔皮素、延胡索酸、五倍子酸、龍膽提取物、葡萄糖酸、甘胺酸、愈創木脂、橙皮苷素、α-羥基苄基次磷酸、羥基肉桂酸、羥基戊二酸、氫醌、n-羥基琥珀酸、羥基酪醇、羥基脲、米糠提取物、乳酸及其鹽、卵磷脂、卵磷脂檸檬酸鹽;R-α-硫辛酸、葉黃素、番茄紅素、蘋果酸、麥芽酚、5-甲氧基色胺、沒食子酸甲基酯、檸檬酸單甘油酯;檸檬酸單異丙基酯;桑色素、β-萘并黃酮、去甲二氫癒創木酸(NDGA)、沒食子酸辛基酯、草酸、檸檬酸棕櫚基酯、吩噻嗪、磷酯醯膽鹼、磷酸、磷酸酯、植酸、植基泛色烯醇(phytylubichromel)、甘椒提取物、沒食子酸丙基酯、聚磷酸酯、槲皮素、反式-白藜蘆醇、迷迭香提取物、迷迭香酸、鼠尾草提取物、芝麻酚、水飛薊素(silymarin)、芥子酸、琥珀酸、檸檬酸硬脂醯基酯、丁香酸、酒石酸、瑞香草酚、生育酚(即,α-、β-、γ-及δ-生育酚)、生育三烯酚(即,α-、β-、γ-及δ-生育三烯酚)、酪醇、香草酸、2,6-二-第三丁基-4-羥甲基苯酚(即,Ionox 100)、2,4-(參-3’,5’-二-第三丁基-4’-羥基苄基)-均三甲苯基(即,Ionox 330)、2,4,5-三羥基丁醯苯、泛醌、第三丁基氫醌(TBHQ)、硫代二丙酸、三羥基丁醯苯、色胺、酪胺、尿酸、維生素K及衍生物、維生素Q10、小麥胚芽油、玉米黃質或其組合。 在其他實施例中,生物活性劑可係一或多種有機酸。有機酸可係羧酸或經取代之羧酸。羧酸可係單-、二-或三-羧酸。一般而言,羧酸可含有約1至約22個碳原子。作為非限制性實例,適宜有機酸包括乙酸、己二酸、丁酸、苯甲酸、肉桂醛、檸檬酸、甲酸、延胡索酸、戊二酸、乙醇酸、乳酸、蘋果酸、苦杏仁酸、丙酸、山梨酸、琥珀酸、酒石酸或其組合。包含羧酸之有機酸之鹽亦適於某些實施例。代表性之適宜鹽包括有機酸之銨、鎂、鈣、鋰、鈉、鉀、硒、鐵、銅及鋅鹽。 在其他實施例中,生物活性劑可係一或多種聚不飽和脂肪酸。適宜聚不飽和脂肪酸(PUFA)包括具有至少18個碳原子及至少兩個碳-碳雙鍵之長鏈脂肪酸,通常呈順式構型。在具體實施例中,PUFA可係ω脂肪酸。PUFA可係ω-3脂肪酸,其中第一雙鍵在自碳鏈之甲基端(即,與羧酸基團相對)之第三碳-碳鍵中產生。ω-3脂肪酸之適宜實例包括所有順式7,10,13-十六碳三烯酸;所有順式-9,12,15-十八碳三烯酸(α-次亞麻油酸,ALA);所有順式-6,9,12,15-十八碳四烯酸(亞麻油酸);所有順式-8,11,14,17-二十碳四烯酸(花生四烯酸);所有順式-5,8,11,14,17-二十碳五烯酸(二十碳五烯酸,EPA);所有順式-7,10,13,16,19-二十二碳五烯酸(鰶油酸,DPA);所有順式-4,7,10,13,16,19-二十二碳六烯酸(二十二碳六烯酸,DHA);所有順式-4,7,10,13,16,19-二十二碳六烯酸;及所有順式-6,9,12,15,18,21-二十四碳烯酸(鯡酸)。在替代實施例中,PUFA可係ω-6脂肪酸,其中第一雙鍵在自碳鏈之甲基端之第六碳-碳鍵中產生。ω-6脂肪酸之實例包括所有順式-9,12-十八碳二烯酸(亞麻油酸);所有順式-6,9,12-十八碳三烯酸(γ-次亞麻油酸,GLA);所有順式-11,14-二十碳二烯酸(二十碳二烯酸);所有順式-8,11,14-二十碳三烯酸(二高-γ-次亞麻油酸,DGLA);所有順式-5,8,11,14-二十碳四烯酸(花生油酸,AA);所有順式-13,16-二十二碳二烯酸(二十二碳二烯酸);所有順式-7,10,13,16-二十二碳四烯酸(腎上腺酸);及所有順式-4,7,10,13,16-二十二碳五烯酸(二十二碳五烯酸)。在另一替代實施例中,PUFA可係ω-9脂肪酸,其中第一雙鍵在自碳鏈之甲基端之第九碳-碳鍵中產生,或係共軛化脂肪酸,其中至少一對雙鍵僅由一個單鍵分開。ω-9脂肪酸之適宜實例包括順式-9-十八碳烯酸(油酸);順式-11-二十碳烯酸(二十碳烯酸);所有順式-5,8,11-二十碳三烯酸(米德酸(mead acid));順式-13-二十二碳烯酸(芥子酸)及順式-15-二十四碳烯酸(神經酸)。共軛化脂肪酸之實例包括9Z,11E-十八-9,11-二烯酸(瘤胃酸);10E,12Z-十八-9,11-二烯酸;8E,10E,12Z-十八碳三烯酸(α-金盞酸);8E,10E,12E-十八碳三烯酸(β-金盞酸);8E,10Z,12E-十八碳三烯酸(蘭花酸);9E,11E,13Z-十八-9,11,13-三烯酸(α-桐酸);9E,11E,13E-十八-9,11,13-三烯酸(β-桐酸);9Z,11Z,13E-十八-9,11,13-三烯酸(梓樹酸)及9E,11Z,13E-十八-9,11,13-三烯酸(石榴酸)。 在其他實施例中,生物活性劑可係一或多種精油。適宜精油包括(但不限於)薄荷油、肉桂葉油、檸檬草油、丁香油、蓖麻油、冬青油、甜橙、綠薄荷油、雪松木油、醛C16、α萜品醇、戊基肉桂醛,柳酸戊基酯、大茴香醛、苄醇、乙酸苄基酯、樟腦、辣椒素、肉桂醛、肉桂醇、香芹酚、香芹醇、檸檬醛、香茅醛、香茅醇、對蒔蘿烴、鄰苯二甲酸二乙基酯、柳酸二甲基酯、二丙二醇、桉油醇(桉樹腦)、丁香酚、異丁香酚、佳樂麝香(galaxolide)、香葉醇、愈創木酚、紫羅蘭酮、山蒼樹、薄荷醇、柳酸薄荷基酯、鄰胺基苯甲酸甲基酯、甲基紫羅蘭酮、柳酸甲酯、水芹烯、胡薄荷油、紫蘇醛、1或2苯基乙基醇、丙酸1苯基乙基酯或丙酸2苯基乙基酯、胡椒醛、乙酸胡椒基酯、胡椒基醇、D蒲勒酮(D pulegone)、萜品4醇、乙酸萜品酯、乙酸4第三丁基環己基酯、百里香油、瑞香草酚、反式茴香腦之代謝物、香草精、乙基香草精、其衍生物或其組合。 在其他實施例中,生物活性劑可係一或多種益生菌或益菌生。益生菌及益菌生包括源自酵母或細菌之促進良好消化健康之試劑。作為非限制性實例,酵母源益生菌及益菌生包括酵母細胞壁源之組分,例如β-葡聚糖、阿拉伯糖木聚糖異麥芽糖、瓊脂寡醣、乳果寡醣、環糊精、乳糖、寡果醣、昆布七糖、乳酮糖、β-半乳寡醣、甘露寡醣、棉子糖、水蘇糖、果寡醣、葡萄糖基蔗糖、蔗糖熱寡醣、異麥芽酮糖、焦糖、菊糖及木寡醣。在例示性實施例中,酵母源試劑可係β-葡聚糖及/或甘露寡醣。酵母細胞壁源組分之來源包括二孢酵母(Saccharomyces bisporus
)、布拉酵母菌(Saccharomyces boulardii
)、啤酒酵母(Saccharomyces cerevisiae
)、莢膜酵母(Saccharomyces capsularis
)、蒙古酵母(Saccharomyces delbrueckii
)、發酵性酵母(Saccharomyces fermentati
)、路德氏酵母(Saccharomyces lugwigii
)、小橢圓酵母(Saccharomyces microellipsoides
)、巴斯德酵母(Saccharomyces pastorianus
)、羅斯酵母(Saccharomyces rosei
)、白色念珠菌(Candida albicans
)、陰溝念珠菌(Candida cloacae
)、熱帶念珠菌(Candida tropicalis
)、產朊念珠菌(Candida utilis
)、念珠狀地絲菌(Geotrichum candidum
)、美洲漢森酵母(Hansenula americana
)、異常漢森酵母(Hansenula anomala
)、溫奇漢森酵母(Hansenula wingei
)及米麴菌(Aspergillus oryzae
)。益生菌及益菌生亦可包括細菌細胞壁源試劑(例如肽聚醣)及源自具有高含量之肽聚醣之革蘭氏陽性細菌之其他組分。例示性革蘭氏陽性細菌包括嗜酸乳桿菌(Lactobacillus acidophilus
)、嗜熱雙歧桿菌(Bifedobact thermophilum
)、長雙歧桿菌(Bifedobat longhum
)、糞鏈球菌(Streptococcus faecium
)、短小芽孢桿菌(Bacillus pumilus
)、枯草桿菌(Bacillus subtilis
)、地衣芽孢桿菌(Bacillus licheniformis
)、嗜酸乳桿菌、酪蛋白乳桿菌(Lactobacillus casei
)、屎腸球菌(Enterococcus faecium
)、雙裂雙歧桿菌(Bifidobacterium bifidium
)、丙酸丙酸桿菌(Propionibacterium acidipropionici
)、費氏丙酸桿菌(Propionibacterium freudenreichii
)及假長雙歧桿菌(Bifidobacterium pseudolongum
)。 在替代實施例中,生物活性劑可係一或多種酶或酶變體。酶之適宜非限制性實例包括澱粉酶、碳水化合物酶、纖維素酶、酯酶、半乳糖酶(galactonase)、半乳糖苷酶、葡聚糖酶、半纖維素酶、水解酶、脂酶、氧化還原酶、果膠酶、肽酶、磷酸酶、磷脂酶、植酸酶、蛋白酶、轉移酶、木聚糖酶或其組合。 在其他實施例中,生物活性劑可係一或多種草藥。如本文中所使用,適宜草藥及草藥衍生物係指草藥提取物及源自植物及植物部分(例如(但不限於)葉、花及根)之物質。非限制性例示性草藥及草藥衍生物包括龍牙草、紫苜蓿、蘆薈、莧菜、白芷、大茴香、刺小蘗、羅勒、蠟楊梅、蜂花粉、樺木、拳參、黑莓、黑升麻、黑胡桃、賜福薊草、藍升麻、藍馬鞭草、貫葉澤蘭、琉璃苣、合香葉、鼠李、筋骨草、牛蒡、辣椒(capsicum)、番椒(cayenne)、藏茴香、鼠李皮、貓薄荷、芹菜、矢車菊、洋甘菊、木餾油樹、繁縷、菊苣、金雞納、丁香、款冬、康福利草(comfrey)、玉蜀黍絲、茅草、莢蒾皮、北美草本威靈仙根(culver’s root)、矢車菊、達米阿那(damiana)、蒲公英、拉線爪、當歸、紫錐花、土木香、麻黃、桉樹、月見草、小米草、假麒麟根、小茴香、葫蘆巴、玄參、亞麻籽、大蒜、龍膽、薑、人參、金印草、積雪草(gotu kola)、膠草(gum weed)、山楂、啤酒花、苦薄荷、辣根、馬尾草、何首烏、繡球花、牛膝草、冰島蘚、愛爾蘭蘚、荷荷巴(jojoba)、杜松、昆布、女屐蘭、檸檬草、甘草、半邊蓮、曼德拉草(mandrake)、萬壽菊、馬郁蘭、蜀葵、槲寄生、毛蕊花、芥菜、沒藥、蕁麻、燕麥桿、俄勒岡葡萄(oregon grape)、木瓜、洋芫荽、西番蓮、桃、胡薄荷、薄荷、長春花、車前草、馬利筋根、商陸、美洲花椒、車前草、苦木、柳葉繡線菊(queen of the meadow)、紅三葉草、紅樹莓、雷蒙德礦泥(redmond clay)、大黃、薔薇果、迷迭香、芸香、紅花、藏紅花、鼠尾草、聖約翰草(St. John’s wort)、洋菝契、黃樟、沙巴棕、美黃岑、美遠志、番瀉葉、薺菜、榆樹、綠薄荷、甘松、孿果藤、柿苓、草莓、紫風鈴木(taheebo)、百里香、熊果(uva ursi)、纈草、紫羅蘭、西洋菜、白橡樹皮、白松樹皮、野櫻桃、野萵苣、野山藥、柳樹、冬青、金縷梅、藥水蘇、苦艾、蓍草、皺葉酸模、北美聖草、絲蘭或其組合。 在其他實施例中,生物活性劑可係一或多種天然顏料。適宜顏料包括(但不限於)珊瑚赤素、茜草素、雙四氧嘧啶、β-阿樸-2’-胡蘿蔔醛、阿樸-2-番茄紅素醛、阿樸-6’-番茄紅素醛、蝦紅素、蝦青素、玄參紅酸醛、菌紅素、艾克森素(aixin)、α-胡蘿蔔素、β-胡蘿蔔素、γ-胡蘿蔔素、β-胡蘿蔔酮、角黃素、辣椒紅素、辣椒紫紅素、枳橙黃質、橘黃質、藏花酸、藏花酸半醛、藏花素、甲殼黃素、隱辣椒質、α-隱黃質、β-隱黃質、菌草黃質(cryptomonaxanthin)、海鞘黃質、癸異戊二烯黃素、去氫金盞花紅素、矽甲藻黃素、1,4-二胺基-2,3-二氫蒽醌、1,4-二羥基蒽醌、2,2’-雙酮螺菌黃素、花菱草類胡蘿蔔素、花菱草類黃素酮、屈曲黃素、鈴蘭色素(foliachrome)、岩藻黃素、尬贊黃素(gazaniaxanthin)、六氫番茄紅素、霍普金斯葉黃素(hopkinsiaxanthin)、羥基球形烯酮、異岩藻黃素、綠藻黃素、葉黃素、黃黃素、番茄紅素、十氫番茄紅素、番茄黃素、桑酮、橘黃質、尼奧克綸(neochrome)、新黃素、壬異戊二烯黃素、OH-綠菌烯、奧克酮(okenone)、顫藻黃質、帕拉森酮(paracentrone)、扇貝醇酮(pectenolone)、蛤黃質、多甲藻素、草分枝桿菌葉黃素(phleixanthophyll)、芬尼酮(phoeniconone)、菲尼黃酮(phoenicopterone)、菲尼黃質(phoenicoxanthin)、酸漿果紅素(physalien)、六氫番茄紅素、皮洛蒼耳素醇(pyrrhoxanthininol)、醌、玫紅品(rhodopin)、玫紅品醒(rhodopinal)、玫紅品醇(rhodopinol)、紫菌紅醇(rhodovibrin)、紫松果黃素、玉紅黃素酮(rubixanthone)、腐菌黃素(saproxanthin)、半-α-胡蘿蔔酮、半-β-胡蘿蔔酮、辛塔葉黃素(sintaxanthin)、管藻黃素(siphonaxanthin)、官藻素、球形烯、福橘黃素(tangeraxanthin)、圓酵母紅素(torularhodin)、圓酵母紅素甲基酯、圓酵母紅素醛、紅酵母烯(torulene)、1,2,4-三羥基蒽醌、臭橘黃素(triphasiaxanthin)、金蓮花色素(trollichrome)、無隔藻黃素(vaucheriaxanthin)、紫黃素(violaxanthin)、瓦明醛(wamingone)、葉黃素、玉米黃質、α-玉米胡蘿蔔素或其組合。 在其他實施例中,生物活性劑可係一或多種醫藥上可接受之試劑。醫藥上可接受之試劑之非限制性實例包括酸/鹼性不穩定藥物、pH依賴性藥物或為弱酸或弱鹼之藥物。酸不穩定藥物之實例包括他汀類(例如,普伐他汀(pravastatin)、氟伐他汀(fluvastatin)及阿托伐他汀(atorvastatin))、抗生素(例如,青黴素G、胺苄青黴素、鏈黴素、紅黴素、克拉黴素(clarithromycin)及阿奇黴素(azithromycin))、核苷類似物[例如,二去氧肌苷(ddI或去羥肌苷)、二去氧腺苷(ddA)、二去氧胞嘧啶(ddC)]、柳酸酯(例如,阿斯匹林(aspirin))、地高辛(digoxin)、安非他酮(bupropion)、胰酶、咪達唑侖(midazolam)及美沙酮(methadone)。僅在酸性pH下可溶之藥物包括硝苯地平(nifedipine)、依莫必利(emonapride)、尼卡地平(nicardipine)、阿莫索羅(amosulalol)、諾司卡品(noscapine)、普羅帕酮(propafenone)、奎寧、雙嘧達莫(dipyridamole)、交沙黴素(josamycin)、地來洛爾(dilevalol)、拉貝洛爾(labetalol)、依尼前列素(enisoprost)及甲硝唑。為弱酸之藥物包括苯巴比妥(phenobarbital)、苯妥英(phenytoin)、齊多夫定(zidovudine,AZT)、柳酸酯(例如,阿斯匹林)、丙酸化合物(例如,布洛芬(ibuprofen))、吲哚衍生物(例如,吲哚美辛(indomethacin))、芬那酸酯(fenamate)化合物(例如,甲氯芬那酸)、吡咯烷酸化合物(例如,妥美汀(tolmetin))、頭孢菌素(cephalosporin)(例如,噻吩頭孢菌素、頭孢力新(cephalaxin)、頭孢若林(cefazolin)、頭孢拉定(cephradine)、頭孢匹林(cephapirin)、頭孢孟多(cefamandole)及頭孢西丁(cefoxitin))、6-氟喹啉酮及前列腺素。為弱鹼之藥物包括腎上腺素能劑(例如,麻黃鹼、去氧麻黃鹼、苯福林(phenylephrine)、腎上腺素、沙丁胺醇(salbutamol)及特布他林(terbutaline))、膽鹼能劑(例如,毒扁豆鹼(physostigmine)及新斯的明(neostigmine))、抗痙攣劑(例如,阿托品(atropine)、乙胺太林(methantheline)及罌粟鹼(papaverine))、箭毒樣劑(例如,氯異吲哚銨(chlorisondamine))、鎮定劑及肌肉鬆弛劑(例如,氟奮乃靜(fluphenazine)、硫利達嗪(thioridazine)、三氟拉嗪(trifluoperazine)、氯丙嗪及三氟丙嗪(triflupromazine))、抗抑鬱藥(例如,阿米替林(amitriptyline)及去甲替林(nortriptyline))、抗組織胺(例如,苯海拉明(diphenhydramine)、氯苯那敏(chlorpheniramine)、乘暈寧(dimenhydrinate)、曲吡那敏(tripelennamine)、奮乃靜(perphenazine)、氯丙非那嗪(chlorprophenazine)及氯非拉明(chlorprophenpyridamine))、心臟活性劑(例如,維拉帕米(verapamil)、地爾硫卓(diltiazem)、戈洛帕米(gallopamil)、桂利嗪(cinnarizine)、普萘洛爾(propranolol)、美托洛爾(metoprolol)及納多洛爾(nadolol))、抗瘧疾藥(例如,氯喹)、止痛藥(例如,丙氧芬(propoxyphene)及哌替啶(meperidine))、抗真菌劑(例如,酮康唑(ketoconazole)及伊曲康唑(itraconazole))、抗微生物劑(例如,頭孢泊肟(cefpodoxime)、普塞(proxetil)及依諾沙星(enoxacin))、咖啡因、茶鹼及嗎啡。在另一實施例中,藥物可係雙膦酸鹽或用於治療骨質疏鬆症之另一藥物。雙膦酸鹽之非限制性實例包括阿侖膦酸鹽(alendronate)、伊班膦酸鹽(ibandronate)、利塞膦酸鹽(risedronate)、唑來膦酸鹽(zoledronate)、帕米膦酸鹽(pamidronate)、奈立膦酸鹽(neridronate)、奧帕膦酸鹽(olpadronate)、依替膦酸鹽(etidronate)、氯膦酸鹽及替魯膦酸鹽(tiludronate)。其他適宜藥物包括雌激素、選擇性雌激素受體調節劑(SERM)及副甲狀腺激素(PTH)藥物。在另一實施例中,藥物可係抗細菌劑。適宜抗生素包括胺基醣苷(例如,阿米卡星(amikacin)、慶大黴素(gentamicin)、康黴素(kanamycin)、新黴素(neomycin)、奈替米星(netilmicin)、鏈黴素及妥布黴素(tobramycin))、碳頭孢烯(carbecephem) (例如,氯碳頭孢(loracarbef))、碳青黴烯(例如,厄他培南(certapenem)、亞胺培南(imipenem)及美羅培南(meropenem))、頭孢菌素(例如,頭孢卓西、頭孢若林、頭孢力新、頭孢可若(cefaclor)、頭孢孟多、頭孢力新、頭孢西丁、頭孢丙烯(cefprozil)、頭孢呋辛(cefuroxime)、希復欣敏(cefixime)、頭孢地尼(cefdinir)、頭孢托侖(cefditoren)、頭孢哌酮(cefoperazone)、頭孢噻肟(cefotaxime)、頭孢泊肟、頭孢他啶(ceftazidime)、頭孢布烯(ceftibuten)、頭孢唑肟(ceftizoxime)及頭孢曲松(ceftriaxone))、巨環內酯(例如,阿奇黴素、克拉黴素、地紅黴素(dirithromycin)、紅黴素及醋竹桃黴素(troleandomycin))、單環β-內醯胺(monobactam)、青黴素(例如,阿莫西林、胺苄青黴素、卡本西林(carbenicillin)、鄰氯青黴素(cloxacillin)、雙氯青黴素、萘夫西林(nafcillin)、扼煞西林(oxacillin)、青黴素G、青黴素V、必倍西林(piperacillin)及替卡西林(ticarcillin))、多肽(例如,桿菌肽、黏菌素及多黏菌素B)、喹啉酮(例如,環丙沙星(ciprofloxacin)、依諾沙星(enoxacin)、加替沙星(gatifloxacin)、左氧氟沙星(levofloxacin)、洛美沙星(lomefloxacin)、莫西沙星(moxifloxacin)、諾氟沙星(norfloxacin)、氧氟沙星(ofloxacin)及曲伐沙星(trovafloxacin))、磺醯胺(例如,磺胺米隆(mafenide)、磺乙醯胺、磺胺甲噻二唑、磺胺塞拉金(sulfasalazine)、磺胺異噁唑及甲氧苄啶-磺胺甲噁唑)及四環素(例如,地美環素(demeclocycline)、去氧羥四環素、米諾四環素(minocycline)及氧四環素)。在替代實施例中,藥物可係抗病毒蛋白酶抑制劑(例如,安瑞那韋(amprenavir)、呋山那韋(fosamprenavir)、茚地那韋(indinavir)、洛匹那韋(lopinavir)/利托那韋(ritonavir)、利托那韋、沙奎那韋(saquinavir)及奈芬那韋(nelfinavir))。在另一實施例中,藥物可係心血管藥物。適宜心血管藥劑之實例包括強心劑(例如,毛地黃(地高辛)、泛癸利酮(ubidecarenone)及多巴胺)、血管舒張劑(例如,硝化甘油、卡托普利(captopril)、雙肼苯噠嗪、地爾硫卓及硝酸異山梨酯(isosorbide dinitrate))、抗高血壓劑(例如,α-甲基多巴(α-methyldopa)、氯噻酮、蛇根鹼(reserpine)、昔洛舍平(syrosingopine)、瑞西那明(rescinnamine)、哌唑嗪、酚妥拉明(phentolamine)、非洛地平(felodipine)、普萘洛爾(propranolol)、吲哚洛爾(pindolol)、拉貝洛爾(labetalol)、可尼丁(clonidine)、卡托普利、依那普利(enalapril)及萊森普利(lisonopril))、β阻斷劑(例如,左布諾洛爾(levobunolol)、吲哚洛爾、馬來酸噻嗎洛爾(timolol maleate)、比索洛爾(bisoprolol)、卡維地洛(carvedilol)及布托沙明(butoxamine))、α阻斷劑(例如,多沙唑嗪(doxazosin)、哌唑嗪、苯氧苯紮明(phenoxybenzamine)、酚妥拉明、坦洛新(tamsulosin)、阿呋唑嗪(alfuzosin)及特拉唑嗪(terazosin))、鈣通道阻斷劑(例如,胺氯地平(amlodipine)、非洛地平、尼卡地平、硝苯地平、尼莫地平(nimodipine)、尼索地平(nisoldipine)、尼群地平(nitrendipine)、拉西地平(lacidipine)、樂卡地平(lercanidipine)、維拉帕米、戈洛帕米及地爾硫卓)及抗凝血劑(例如,雙嘧莫達(dipyrimadole))。 (iii) 賦形劑
營養組合物中可包括各種賦形劑。適宜賦形劑包括填充劑、黏合劑、pH調整劑、崩解劑、分散劑、防腐劑、潤滑劑、著色劑、調味劑、味道掩蔽劑或其組合。一般而言,賦形劑係適用於營養組合物中之級別。 在一些實施例中,賦形劑可包含至少一種填充劑。適宜填充劑(亦稱為稀釋劑)之非限制性實例包括纖維素、微晶纖維素、纖維素醚(例如,乙基纖維素、甲基纖維素、羥丙基纖維素、羥丙基甲基纖維素、羧甲基纖維素鈉等)、纖維素酯(即,乙酸纖維素、丁酸纖維素及其混合物)、澱粉(例如,玉米澱粉、稻穀澱粉、馬鈴薯澱粉、木薯澱粉澱粉及諸如此類)、改質澱粉、預膠凝澱粉、磷酸鹽化澱粉、澱粉-乳糖、澱粉-碳酸鈣、羥基乙酸澱粉鈉、葡萄糖、果糖、蔗糖、乳糖、木糖、乳糖醇、甘露醇、麥芽糖醇、山梨醇、木糖醇、麥芽糊精、海藻糖、碳酸鈣、硫酸鈣、磷酸鈣、矽酸鈣、碳酸鎂、氧化鎂、滑石或其組合。在其他實施例中,填充劑可包含如下文部分(III)(b)中所指定之聚合物。 在其他實施例中,賦形劑可包含至少一種黏合劑。適宜黏合劑之實例包括(但不限於)澱粉(例如,玉米澱粉、馬鈴薯澱粉、小麥澱粉、稻穀澱粉及諸如此類)、預膠凝澱粉、水解澱粉、纖維素、微晶纖維素、纖維素衍生物(例如,甲基纖維素、乙基纖維素、羥丙基纖維素、羥丙基甲基纖維素、羧甲基纖維素鈉及諸如此類)、醣(例如,蔗糖、乳糖等)、糖醇(例如,麥芽糖醇、山梨醇、木糖醇、聚乙二醇及諸如此類)、海藻酸鹽(例如,海藻酸、海藻酸鹽、海藻酸鈉等)、樹膠(例如,阿拉伯樹膠、瓜爾膠(guar gum)、結蘭膠(gellan gum)、黃原膠及諸如此類)、果膠、明膠、C12-C18脂肪酸醇、聚乙烯基吡咯啶酮(亦稱為共聚維酮(copovidone))、聚氧化乙烯、聚乙二醇、聚乙烯醇、蠟(例如,小燭樹蠟(candelilla wax)、棕櫚蠟、蜂蠟等)或前述任一者之組合。 在其他實施例中,賦形劑可係pH調整劑。作為非限制性實例,pH調整劑包括有機羧酸(例如,乙酸、抗壞血酸、檸檬酸、甲酸、乙醇酸、葡萄糖酸、乳酸、蘋果酸、馬來酸、丙酸、琥珀酸、酒石酸等)或其鹽及其他酸(例如,鹽酸、硼酸、硝酸、磷酸、硫酸等)、鹼金屬或銨之碳酸鹽、酸式碳酸鹽、氫氧化物、磷酸鹽、硝酸鹽及矽酸鹽;及有機鹼(例如吡啶、三乙胺(即,單乙醇胺)、二異丙基乙胺、N甲基嗎啉、N,N二甲基胺基吡啶)。 在其他實施例中,賦形劑可係崩解劑。適宜崩解劑之實例包括(但不限於)聚維酮、交聚維酮、交聯羧甲基纖維素鈉、羧甲基纖維素鈉、羧甲基纖維素鈣、羥基乙酸澱粉鈉、纖維素、微晶纖維素、甲基纖維素、二氧化矽(亦稱為膠體二氧化矽)、海藻酸鹽(例如,海藻酸、海藻酸鹽、海藻酸鈉等)、黏土(例如,膨潤土)或其組合。 在替代實施例中,賦形劑可係分散劑。適宜分散劑包括(但不限於)澱粉、海藻酸、聚乙烯基吡咯啶酮、瓜爾膠、高嶺土(kaolin)、膨潤土、純化木纖維素、羥基乙酸澱粉鈉、同形(isoamorphous)矽酸鹽及微晶纖維素作為高HLB乳化劑表面活性劑。 在其他實施例中,賦形劑可係防腐劑。適宜防腐劑之非限制性實例包括抗氧化劑(例如,α-生育酚、棕櫚酸抗壞血酸酯、丁基羥基茴香醚、二丁基羥基甲苯、檸檬酸、二氫癒創木酸、抗壞血酸鉀、山梨酸鉀、沒食子酸丙基酯、硫酸氫鈉、異抗壞血酸鈉、焦亞硫酸鈉、山梨酸、4-氯-2,6-二第三丁基酚等)、抗微生物劑(例如,苄醇、氯化十六烷基吡啶、甘油、對羥基苯甲酸酯、丙二醇、山梨酸鉀、苯甲酸鈉、山梨酸、丙酸鈉及諸如此類)或其組合。 在其他實施例中,賦形劑可係潤滑劑。適宜潤滑劑之實例包括金屬硬脂酸鹽(例如硬脂酸鎂、硬脂酸鈣、硬脂酸鋅)、聚乙二醇、泊洛沙姆(poloxamer)、膠體二氧化矽、山崳酸甘油酯、輕質礦物油、氫化植物油、月桂基硫酸鎂、三矽酸鎂、聚氧乙烯單硬脂酸鹽、硬脂醯延胡索酸鈉、硬脂延胡索酸鈉、苯甲酸鈉、月桂基硫酸鈉、硬脂酸、sterotex、滑石或其組合。 在其他實施例中,賦形劑可係色彩添加劑。適宜色彩添加劑包括(但不限於)食品、藥物及化妝品色彩(FD&C)、藥物及化妝品色彩(D&C)或外用藥物及化妝品色彩(Ext. D&C).藥物及化妝品色彩(D&C)或外用藥物及化妝品色彩(Ext. D&C)。該等色彩或染料以及其相應色澱及某些天然及衍生性著色劑可適用於該等組合物中。 在替代實施例中,賦形劑可係調味劑。調味劑可選自合成調味油及調味芳香族化合物及/或天然油、來自植物、葉、花、果實之提取物及其組合。舉例而言,該等調味劑可包括桂皮油、冬青油、薄荷油、苜蓿油、乾草油、大茴香油、桉樹油、香草、橘皮油(例如檸檬油、橙油、葡萄油及葡萄柚油)及水果香精(例如蘋果、桃、梨、草莓、樹莓、櫻桃、李、菠蘿及杏)。在另一實施例中,賦形劑可包括甜味劑。作為非限制性實例,甜味劑可選自葡萄糖(玉米糖漿)、右旋糖、轉化糖、果糖及其混合物(在不用作載劑時);糖精及其各種鹽,例如鈉鹽;二肽甜味劑,例如天冬甜素;二氫查耳酮化合物、甘草素;甜葉菊源甜味劑;蔗糖之氯衍生物,例如蔗糖素;糖醇,例如山梨醇、甘露醇、木糖醇及諸如此類。亦涵蓋氫化澱粉水解產物及合成甜味劑3,6-二氫-6-甲基-1,2,3-噁噻嗪-4-酮-2,2-二氧化物,尤其鉀鹽(乙醯胺基磺酸-K)及其鈉鹽及鈣鹽。在另一實施例中,賦形劑可包括味道掩蔽劑。 在一些實施例中,賦形劑可係味道掩蔽劑。適宜味道掩蔽劑包括纖維素羥基丙基醚(HPC);低取代羥基丙基醚(L-HPC);纖維素羥基丙基甲基醚(HPMC);甲基纖維素聚合物及其混合物;聚乙烯基醇(PVA);羥乙基纖維素;羧甲基纖維素及其鹽;聚乙烯基醇及聚乙二醇共聚物;甘油單酯或甘油三酯;聚乙二醇;丙烯酸聚合物;丙烯酸聚合物與纖維素醚之混合物;乙酸鄰苯二甲酸纖維素;或其組合。(b) 工業組合物
在其他實施例中,包含本文中所揭示調配物之組合物可具有工業用途。舉例而言,該等組合物可在半導體、能量或電子工業中用作蝕刻劑或電子製程化學品。在其他實施例中,組合物可用作製造用於飲料容器、食品容器、食品包裝產品、餐飲服務用具、消費品包裝及諸如此類之塑膠之聚合物或共聚物。在其他實施例中,組合物可用作特用塗層應用(例如,塗覆醫療器械或量子點塗層)中之聚合物/共聚物薄膜。在替代實施例中,組合物可用作金屬處理、紡織品處理、木材及紙處理、油收穫及/或油處理及回收製程中之潤濕劑、反乳化劑或處理助劑。 因此,本文中所詳述之組合物包含含有式(I)化合物之特用調配物及一或多種選自以下之試劑:溶劑、表面活性劑、潤濕劑、聚合物、塑化劑、黏合劑、填充劑、增稠劑、泡沫控制劑、分散劑、崩解劑、pH調整劑、螯合劑、防腐劑、顏料、熱穩定劑、UV/光穩定劑、阻燃劑、殺生物劑、處理助劑、熱改質劑、抗衝擊改質劑、發泡劑、潤滑劑、成核劑或其組合。 (i) 試劑
在一些實施例中,試劑可係溶劑。溶劑可為有機或無機溶劑。適宜有機溶劑包括(但不限於)含氧溶劑(例如醇、酯、酮、二醇醚、二醇醚酯、羥基醚及烷氧基丙醇)、烴溶劑(例如脂肪族及芳香族烴)及鹵化溶劑(例如氯化烴)。適宜無機溶劑包括水及氨。 在其他實施例中,試劑可係表面活性劑。表面活性劑可係非離子表面活性劑、陰離子表面活性劑或陽離子表面活性劑。適宜非離子表面活性劑(包括無淨電荷之兩性離子表面活性劑)之非限制性實例包括醇乙氧基化物、烷基酚乙氧基化物(例如,壬基苯基乙氧基化物)、硫醇乙氧基化物、脂肪酸乙氧基化物、甘油酯、己醣醇酯、胺乙氧基化物、烷基醯胺乙氧基化物及醯亞胺乙氧基化物。適宜陰離子表面活性劑包括(但不限於)烷基硫酸鹽、烷基醚硫酸鹽、硫酸化烷醇醯胺、硫酸甘油酯、十二烷基苯磺酸鹽、烷基苯磺酸鹽、α烯烴磺酸鹽及磺基羧酸化合物。適宜陽離子表面活性劑之非限制性實例包括烷基胺、四級烷基銨、酯胺及醚胺。 在其他實施例中,試劑可係潤濕劑。適宜潤濕劑包括(但不限於)非離子表面活性劑(例如聚氧乙烯表面活性劑、嵌段共聚物表面活性劑、烷基聚葡萄糖苷表面活性劑、經修飾之甲基封端嵌段共聚物表面活性劑、多具支鏈共聚物表面活性劑)陰離子表面活性劑及陽離子表面活性劑。 在替代實施例中,試劑可係聚合物。之實例適宜聚合物包括(但不限於)以下之聚合物:丙烯酸酯、丙烯酸、丙烯腈、胺基丙烯酸酯、琥珀酸伸烷基酯、草酸伸烷基酯、醯胺、胺、酸酐、芳基化物、碳酸酯、纖維素、纖維素衍生物、己內酯、氰基丙烯酸酯、二氫吡喃、二噁烷、二氧雜環己酮、醚醚酮、乙二醇、環氧乙烷、延胡索酸酯、羥基烷酸酯、羥基-酯、醯亞胺、縮酮、乳酸交酯、甲基丙烯酸酯、甲基烯烴、原酸酯、膦嗪、吡啶、吡啶衍生物、苯乙烯、苯乙烯衍生物、對苯二甲酸酯、三亞甲基碳酸酯、胺基甲酸酯、乙酸乙烯酯、乙烯基酯、乙烯基酮、乙烯基鹵化物、其衍生物、異構物、混合物或其共聚物。 在其他實施例中,試劑可係塑化劑。適宜塑化劑之實例包括(但不限於)己二酸酯、癸二酸酯/壬二酸酯、苯甲酸酯/二苯甲酸酯、檸檬酸酯、環己酸酯、環氧酯、磷酸酯、泊洛沙姆、聚乙二醇、鄰苯二甲酸酯、對苯二甲酸酯、偏苯三酸酯或其組合。 在其他實施例中,試劑可係黏合劑(即,成膜劑)。適宜黏合劑之非限制性實例包括丙烯酸系樹脂、乳膠(即,乙烯基-丙烯酸系或PVA)樹脂、乙酸乙烯酯/乙烯(VAE)樹脂、聚酯樹脂、酚樹脂、醇酸樹脂、胺基甲酸酯樹脂、三聚氰胺樹脂及環氧樹脂。 在其他實施例中,試劑可係填充劑。適宜填充劑之非限制性實例包括纖維素、甲基纖維素、羧甲基纖維素、微晶纖維素、硫酸鈣、碳酸鈣、碳酸鎂、磷酸氫鈣、碳酸鎂、氧化鎂、矽酸鈣、氯化鈉、二氧化鈦、滑石、玻璃、雲母、煅燒黏土、赤泥、白雲石、改質澱粉、乳糖、蔗糖、甘露醇、山梨醇或其組合。 在替代實施例中,試劑可係增稠劑(即,流變添加劑)。適宜增稠劑包括(但不限於)纖維素醚(例如羥基纖維素、羥丙基纖維素、羥甲基丙基纖維素、羥乙基纖維素、羧甲基纖維素、甲基羥乙基纖維素)、聚乙烯基吡咯啶酮、聚(乙烯基吡啶-N-氧化物)、丙烯酸系樹脂、乙烯基丙烯酸系樹脂、膨潤土、澱粉、樹膠及其組合。 在其他實施例中,試劑可係泡沫控制劑(即,消泡劑)。適宜泡沫控制劑之非限制性實例包括基於環氧乙烷/環氧丙烷共聚物之消泡劑、基於聚合物具有矽主鏈(例如,聚矽氧油、聚矽氧烷等)之消泡劑、基於油之消泡劑(例如,礦物油、植物油、長鏈脂肪酸或脂肪酸酯)或粉末消泡劑(例如,二氧化矽)。 在其他實施例中,試劑可係分散劑。適宜分散劑包括(但不限於)膦酸鹽、羧甲基菊糖、六偏磷酸鈉、三聚磷酸鈉、焦磷酸四鈉、三聚磷酸鉀及丙烯酸系聚合物。 在其他實施例中,試劑可係崩解劑。適宜崩解劑包括(但不限於)澱粉(例如玉米澱粉、馬鈴薯澱粉、其預膠凝及改質澱粉)、甜味劑、黏土(例如膨潤土)、微晶纖維素、海藻酸鹽、羥乙酸澱粉鈉、樹膠(例如瓊脂、瓜爾膠、刺槐豆膠、刺梧桐膠、果膠及黃蓍膠)。 在替代實施例中,試劑可係pH調整劑。適宜pH調整劑之非限制性實例包括有機羧酸(例如,乙酸、抗壞血酸、檸檬酸、甲酸、乙醇酸、葡萄糖酸、乳酸、蘋果酸、馬來酸、丙酸、琥珀酸、酒石酸等)或其鹽及其他酸(例如,鹽酸、硼酸、硝酸、磷酸、硫酸等)、鹼金屬或銨之碳酸鹽、酸式碳酸鹽、氫氧化物、磷酸鹽、硝酸鹽及矽酸鹽;及有機鹼(例如吡啶、三乙胺(即,單乙醇胺)、二異丙基乙胺、N甲基嗎啉、N,N二甲基胺基吡啶。 在其他實施例中,試劑可係螯合劑。適宜螯合劑包括(但不限於) EDTA、DTPA、HEDP、HEDTA、NTA、HEIDA、PBTC、膦酸鹽、羧甲基菊糖、三磷酸鈉、六偏磷酸鈉、三聚磷酸鈉、焦磷酸四鈉、三聚磷酸鉀、焦磷酸四鉀、檸檬酸、葡萄糖酸、葡萄糖酸鈉及DTPMP。 在其他實施例中,試劑可係防腐劑。適宜防腐劑之非限制性實例包括抗氧化劑(例如α-生育酚或抗壞血酸鹽)及抗微生物劑(例如對羥基苯甲酸酯、氯丁醇、酚、戊二醛、苯甲酸、四級銨鹽、布羅波爾(bronopol)、過氧化氫、二氯異氰尿酸鈉及次氯酸鈉)。 在其他實施例中,試劑可係顏料(或著色劑)。顏料係精細研磨之粒子或粉末,其提供對漆料調配物之著色及遮蓋。顏料可係底漆顏料,其提供白度或色彩及遮蓋,或係體質顏料,其確保底漆顏料之適當間隔以避免聚集及遮蓋損失。在一些實施例中,底漆顏料可係二氧化鈦或氧化鋅,即主要之白色顏料。底漆顏料亦可包括有機或無機色彩顏料(或色彩試劑)。色彩顏料或色彩試劑為業內所熟知。色彩顏料之非限制性實例包括鋅黃、聯苯胺黃、氧化鉻綠、酞青素綠、酞青素藍、朱紅、顏料棕6、紅色170、二噁嗪紫羅蘭、碳黑及氧化鐵(II)。適宜體質顏料(或增效劑)包括(但不限於)黏土(例如,高嶺土黏土)、二氧化矽、矽酸鹽、矽藻土(diatomaceous silica)、石英砂、碳酸鈣(亦稱為石灰石)、重晶石、滑石及氧化鋅。適宜著色劑包括(但不限於)食品、藥物及化妝品色彩(FD&C)、藥物及化妝品色彩(D&C)、外用藥物及化妝品色彩(Ext. D&C),以及行業內已知之其他染料。 在一些實施例中,試劑可係熱穩定劑。熱穩定劑通常包含金屬化合物,例如金屬皂、金屬鹽及有機金屬化合物。含於熱穩定劑中之主要金屬包括鈣、錫、鋅、鋇及鉛。適宜熱穩定劑之非限制性實例包括鈣-鋅穩定劑、鈣-有機物穩定劑(例如,乙醯基丙酮鈣、乙醯基丙酮鋅)、硬脂酸鈣、硬脂酸鋅、甲基錫穩定劑、硫醇有機錫及其組合。 在其他實施例中,試劑可係UV穩定劑或光穩定劑。適宜UV穩定劑或光穩定劑包括(但不限於) 2-(2’-羥基-5’-甲基苯基)-苯并三唑、2-羥基-4-辛氧基二苯甲酮、2-(2’-羥基-5’-第三辛基苯基)苯并三唑、2-(2’-羥基-3,5’-二第三丁基苯基)-苯并三唑、2-(2’-羥基-3,5’-二第三丁基苯基)-5-氯苯并三唑、2-(2’-羥基-3’-第三丁基-5’-甲基苯基)-5-氯苯并三唑、2-羥基-4-甲氧基二苯甲酮、琥珀酸聚[1-(2’-羥基乙基)-2,2,6,6-四甲基-4-羥基六氫吡啶基]酯、雙(2,2,6,6-四甲基-4-六氫吡啶)癸二酸酯、2-羥基-4-甲氧基二苯甲酮-5-磺酸、2-苯基-1H-苯并[d]咪唑-5-磺酸、2-(2’-羥基-3’-5’-二第三丁基)苯并三唑、2,2’-二羥基-4-甲氧基苯并三唑、受阻胺光穩定劑(HALS)、二氧化鈦及其組合。 在其他實施例中,試劑可係阻燃劑或消煙劑。適宜阻燃劑/消煙劑之非限制性實例包括三水合氧化鋁、氫氧化鎂、三氧化銻、水菱鎂礦、銅黏土、鉬酸鹽、硼酸鹽、氯橋酸(chlorendic acid)衍生物、氯化石蠟、十溴二苯醚、十溴二苯乙烷、溴化聚苯乙烯、溴化環氧寡聚物、四溴鄰苯二甲酸酐、四雙酚A、六溴環十二烷、磷酸三苯基酯、間苯二酚雙(二苯基磷酸酯)、雙酚A二苯基磷酸酯、磷酸三甲苯酯、甲基膦酸二甲基酯、二乙基亞膦酸氧化鋁、磷酸參(2,3-二溴丙基)酯、磷酸參(1,3-二氯-2-丙基)酯、二磷酸(2-氯乙基)二氯異戊基酯及其組合。 在其他實施例中,試劑可係殺生物劑。適宜殺生物劑之非限制性實例包括2-乙基己酸銅、匹塞翁鋅(zinc pyrithione)、10,10’-氧基雙酚噁胂、二碘甲基對甲苯基碸、丁基胺基甲酸3-碘-2-丙炔基酯、N-(三氯甲硫基)鄰苯二甲醯亞胺、正辛基-、二氯正辛基-異噻唑啉酮、丁基苯并異噻唑啉酮及其組合。 在其他實施例中,試劑可係處理助劑。處理助劑包括(但不限於)丙烯酸處理助劑、丙烯酸酯共聚物、苯乙烯-丙烯腈共聚物、甲基丙烯酸甲酯-苯乙烯-乙酸乙烯酯共聚物及其組合。 在其他實施例中,試劑可係熱改質劑。適宜熱改質劑之非限制性實例包括丙烯酸甲酯-丁二烯-苯乙烯三元共聚物(例如,Clearstrength E-920)、丙烯腈-丁二烯-苯乙烯共聚物、α-甲基苯乙烯共聚物、乙烯-丙烯共聚物、乙烯共聚物、丙烯酸酯改質劑(例如,甲基丙烯酸苯氧基乙基酯、乙二醇二甲基丙烯酸酯、1,3-丁二醇二甲基丙烯酸酯、己二醇二甲基丙烯酸酯、三甲基丙烯酸酯、三羥甲基丙烷三甲基丙烯酸酯)及其組合。 在其他實施例中,試劑可係抗衝擊改質劑。抗衝擊改質劑包括(但不限於)乙烯共聚物、乙烯/丙烯酸丁酯/甲基丙烯酸縮水甘油酯共聚物、乙烯-丙烯共聚物、丙烯酸抗衝擊改質劑、丙烯腈-丁二烯-苯乙烯共聚物、丙烯腈-苯乙烯-丙烯酸酯共聚物、苯乙烯-丁二烯-苯乙烯共聚物、苯乙烯-乙烯-丁二烯-苯乙烯共聚物、氯化聚乙烯、交聯聚丙烯酸酯及其組合。 在替代實施例中,試劑可係發泡劑。適宜發泡劑之非限制性實例包括偶氮二甲醯胺或其他基於偶氮之化合物、硝酸肼或其他基於肼之化合物、吸熱化學發泡劑(CFA)、放熱CFA、吸熱/放熱CFA摻合物、烴(例如,戊烷、異戊烷、環戊烷)、異氰酸酯及其組合。 在其他實施例中,試劑可係潤滑劑或共穩定劑。適宜潤滑劑或共穩定劑包括(但不限於)多元醇、環氧化酯、環氧化油、聚乙烯蠟、氧化聚乙烯蠟、石蠟、金屬皂(例如,硬脂酸鈣、硬脂酸鋅等)、酯(例如,聚乙烯單/二/三硬脂酸酯、甘油單硬脂酸酯、單油酸甘油基酯、褐煤蠟(Montan wax)、硬脂酸硬脂醯基酯、鄰苯二甲酸二硬脂醯基酯)、醯胺(例如,芥酸醯胺、油醯胺、硬脂醯胺、伸乙基雙(硬脂醯胺)等)、脂肪酸(例如,月桂酸、硬脂酸、油酸等)、脂肪醇(例如,鯨蠟醇、硬脂醇、山崳醇等)及其組合。 在其他實施例中,試劑可係成核劑。適宜成核劑之非限制性實例包括N,N’-伸乙基-雙-硬脂醯胺(EBS)、LAK-301 (芳香族磺酸鹽衍生物)、滑石、苯甲酸鈉、碳酸鈣、辛二酸之鈣鹽、庚二酸之鈣鹽、β-環糊精、聚甲醛、苯基膦酸鎂、苯基膦酸鈉或苯基膦酸鋅、氰尿酸、尿嘧啶、胸腺嘧啶、硝基咪唑、脂肪酸醯胺及其組合。(c) 農用組合物
在其他實施例中,組合物可在農業、林業或園林綠化反面具有用途。舉例而言,組合物可用作農用化學品調配物、可乳化農業濃縮物等。該等組合物包含含有式(I)化合物之特用調配物及至少一種選自以下之試劑:除草劑、殺真菌劑、殺蟲劑、肥料、溶劑、表面活性劑、黏合劑、填充劑、潤濕劑、增稠劑、泡沫控制劑、分散劑、崩解劑、pH調整劑、螯合劑、防腐劑、顏料或其組合。 (i) 試劑
在一些實施例中,試劑可係一或多種除草劑。適宜除草劑之非限制性實例包括咪唑啉酮、乙草胺、三氟羧草醚、苯草醚、丙烯醛、AKH-7088、甲草胺、禾草滅(alloxydim)、莠滅淨(ametryn)、醯嘧磺隆(amidosulfuron)、殺草強(amitrole)、胺基磺酸銨、莎稗磷(anilofos)、磺草靈(asulam)、草脫淨(atrazine)、草芬定(azafenidin)、四唑嘧磺隆、BAS 620H、BAS 654 00H、BAY FOE 5043、草除靈(benazolin)、氟草胺(benfluralin)、呋草黃(benfuresate)、苄嘧磺隆(bensulfuron-methyl)、地散磷(bensulide)、本達隆(bentazone)、吡草酮(benzofenap)、甲羧除草醚(bifenox)、雙丙胺磷(bilanafos)、雙草醚(bispyribac-sodium)、除草定(bromacil)、溴丁醯草胺(bromobutide)、殺草全(bromofenoxim)、溴苯腈(bromoxynil)、丁基拉草(butachlor)、抑草磷(butamifos)、丁樂靈(butralin)、丁苯草酮(butroxydim)、丁草特(butylate)、唑草胺(cafenstrole)、長殺草(carbetamide)、唑酮草酯(carfentrazone-ethyl)、甲氧除草醚(chlormethoxyfen)、草滅平(chloramben)、氯溴隆(chlorbromuron)、殺草敏(chloridazon)、氯嘧磺隆(chlorimuron-ethyl)、氯乙酸、綠麥隆(chlorotoluron)、氯苯胺靈(chlorpropham)、氯磺隆(chlorsulfuron)、二甲基敵草索(chlorthal-dimethyl)、草克樂(chlorthiamid)、環庚草醚(cinmethylin)、醚磺隆(cinosulfuron)、剋草同(clethodim)、炔草酯(clodinafop-propargyl)、異噁草酮(clomazone)、氯甲醯草胺(clomeprop)、克草立特(clopyralid)、氯酯磺草胺(cloransulam-methyl)、草淨津(cyanazine)、草滅特(cycloate)、環磺隆(cyclosulfamuron)、環殺草(cycloxydim)、丁基賽伏草(cyhalofop-butyl)、2,4-D、殺草隆(daimuron)、茅草枯(dalapon)、棉隆(dazomet)、2,4DB、甜菜安(desmedipham)、敵草淨(desmetryn)、麥草畏(dicamba)、敵草腈(dichlobenil)、2,4-滴丙酸(dichlorprop)、2,4-滴丙酸-P (dichlorprop-P)、禾草靈(diclofop-methyl)、野燕枯(difenzoquat metilsulfate)、吡氟醯草胺(diflufenican)、噁唑隆(dimefuron)、哌草丹(dimepiperate)、二甲草胺(dimethachlor)、異戊乙淨(dimethametryn)、二甲酚草胺(dimethenamid)、噻節因(dimethipin)、二甲基胂酸、撻乃安(dinitramine)、敵蟎普(dinocap)、特樂酚(dinoterb)、草乃敵(diphenamid)、二溴敵草快(diquat dibromide)、氟硫草定(dithiopyr)、達有龍(diuron)、DNOC、EPTC、戊草丹(esprocarb)、丁氟消草(ethalfluralin)、胺苯磺隆(ethametsulfuron-methyl)、乙氧呋草黃(ethofumesate)、乙氧嘧磺隆、乙氧苯草胺、精噁唑禾草靈(fenoxaprop-P-ethyl)、非草隆(fenuron)、硫酸亞鐵、麥草伏-M (flamprop-M)、啶嘧磺隆(flazasulfuron)、丁基吡氟禾草靈、丁基吡氟禾草靈-P、氟消草(fluchloralin)、唑嘧磺草胺(flumetsulam)、氟烯草酸、丙炔氟草胺、伏草隆(fluometuron)、乙羧氟草醚、氟胺草唑(flupoxam)、氟丙酸(flupropanate)、氟啶嘧磺隆鈉(flupyrsulfuron-methyl-sodium)、抑草丁(flurenol)、氟啶草酮(fluridone)、氟咯草酮(flurochloridone)、氟草煙(fluroxypyr)、呋草酮(flurtamone)、嗪草酸甲酯、氟磺胺草醚、殺木膦(fosamine)、草銨膦(glufosinate-ammonium)、草甘膦(glyphosate)、草丁膦(glyphosinate)、氯吡嘧磺隆(halosulfuron-methyl)、吡氟氯禾靈(haloxyfop)、HC-252、環嗪酮(hexazinone)、咪草酸(imazamethabenz-methyl)、甲氧咪草煙(imazamox)、滅草煙(imazapyr)、滅草喹(imazaquin)、咪唑乙煙酸(imazethapyr)、咪唑磺隆(imazosuluron)、咪唑啉酮(imidazilinone)、茚草酮(indanofan)、碘苯腈(ioxynil)、異丙隆(isoproturon)、異噁隆(isouron)、異噁醯草胺(isoxaben)、異噁唑草酮、乳氟草靈(lactofen)、環草定(lenacil)、利穀隆(linuron)、MCPA、脫禾草(MCPA-thioethyl)、MCPB、2-甲基-4-氯丙酸(mecoprop)、2-甲基-4-氯丙酸-P (mecoprop-P)、苯噻草胺(mefenacet)、苯嗪草酮(metamitron)、滅草胺(metazachlor)、甲基苯噻隆(methabenzthiazuron)、甲基胂酸、甲基殺草隆(methyldymron)、異硫氰酸甲基酯、甲氧苯草隆(metobenzuron)、秀穀隆(metobromuron)、異丙甲草胺(metolachlor)、磺草唑胺(metosulam)、甲氧隆(metoxuron)、嗪草酮(metribuzin)、甲磺隆(metsulfuron-methyl)、草達滅(molinate)、綠穀隆(monolinuron)、萘丙胺(naproanilide)、敵草胺(napropamide)、萘草胺(naptalam)、草不隆(neburon)、煙嘧磺隆(nicosulfuron)、壬酸、達草滅(norflurazon)、油酸(脂肪酸)、坪草丹(orbencarb)、黃草消(oryzalin)、丙炔噁草酮、噁草酮、環氧嘧磺隆(oxasulfuron)、乙氧氟草醚、二氯百草枯(paraquat dichloride)、克草猛(pebulate)、施得圃(pendimethalin)、五氯酚、蔬草滅(pentanochlor)、環戊噁草酮、石油(petroleum oils)、苯敵草(phenmedipham)、毒莠定(picloram)、哌草磷(piperophos)、丙草胺(pretilachlor)、甲基氟嘧磺隆(primisulfuron-methyl)、胺基丙氟靈(prodiamine)、撲滅通(prometon)、撲草淨(prometryn)、毒草安(propachlor)、敵稗(propanil)、喔草酯(propaquizafop)、撲滅津(propazine)、苯胺靈(propham)、異丙草胺(propisochlor)、戊炔草胺(propyzamide)、苄草丹(prosulfocarb)、氟磺隆(prosulfuron)、吡草醚(pyraflufen-ethyl)、吡唑特(pyrazolynate)、吡嘧磺隆(pyrazosulfuron-ethyl)、苄草唑(pyrazoxyfen)、稗草畏(pyributicarb)、噠草特(pyridate)、嘧草醚(pyriminobac-methyl)、嘧硫草醚(pyrithiobac-sodium)、快克草(quinclorac)、喹草酸(quinmerac)、滅藻醌(quinoclamine)、喹禾靈(quizalofop)、喹禾靈-P、玉嘧磺隆(rimsulfuron)、西殺草(sethoxydim)、環草隆(siduron)、西瑪津(simazine)、西草淨(simetryn)、氯酸鈉、STS系統(磺醯脲)、磺草酮、甲磺草胺、甲嘧磺隆(sulfometuron-methyl)、磺醯磺隆(sulfosulfuron)、硫酸、煤焦油、2,3,6-TBA、TCA-鈉、牧草胺(tebutam)、丁噻隆(tebuthiuron)、特草定(terbacil)、特丁通(terbumeton)、特丁津(terbuthylazine)、特丁淨(terbutryn)、甲氧噻草胺 (thenylchlor)、噻草定(thiazopyr)、甲基噻吩磺隆(thifensulfuron-methyl)、殺草丹(thiobencarb)、仲草丹(tiocarbazil)、三甲苯草酮(tralkoxydim)、野麥畏(tri-allate)、醚苯磺隆(triasulfuron)、三嗪氟草胺(triaziflam)、苯磺隆(tribenuron-methyl)、綠草定(triclopyr)、草達津(trietazine)、氟樂靈(trifluralin)、氟胺磺隆(triflusulfuron-methyl)、滅草猛(vernolate)或其組合。 在其他實施例中,試劑可係一或多種殺真菌劑。適宜殺真菌劑包括(但不限於)胺基甲酸酯殺真菌劑,例如3,3’-伸乙基雙(四氫-4,6-二甲基-2H-1,3,5-噻二嗪-2-硫酮)、伸乙基雙(二硫代胺基甲酸)鋅或伸乙基雙(二硫代胺基甲酸)鋅錳、雙(二甲基二硫代胺甲醯基)二硫化物、伸丙基雙(二硫代胺基甲酸)鋅、雙(二甲基二硫代胺甲醯基)乙二胺、二甲基二硫代胺基甲酸鎳、1-(丁基胺甲醯基)-2-苯并咪唑胺基甲酸甲基酯、1,2-雙(3-甲氧基羰基-2-硫脲基)苯、1-異丙基胺甲醯基-3-(3,5-二氯苯基)乙內醯脲、N-羥甲基-N-甲基二硫代胺基甲酸鉀及5-甲基-10-丁氧基羰基胺基-10,11-去氫二苯并(b,f)氮呯;吡啶殺真菌劑,例如雙(1-羥基-2(1H)吡啶硫代硫酸)鋅及2-吡啶硫醇-1-氧化物鈉鹽;磷殺真菌劑,例如S-苄基硫代磷酸O,O-二異丙基酯及S,S-二苯基二硫代磷酸O-乙基酯;酞醯亞胺殺真菌劑,例如N-(2,6-二乙基苯基)酞醯亞胺及N-(2,6-二乙基苯基)-4-甲基酞醯亞胺;二羧基醯亞胺殺真菌劑,例如N-三氯甲硫基-4-環己烯-1,2-二羧基醯亞胺及N-四氯乙基硫基-4-環己烯-1,2-二羧基醯亞胺;氧硫雜環己二烯(oxathine)殺真菌劑,例如5,6-二氫-2-甲基-1,4-氧硫雜環己二烯-3-甲醯苯胺基-4,4-二氧化物及5,6-二氫-2-甲基-1,4-氧硫雜環己二烯-3-苯胺基甲醯;萘并醌殺真菌劑,例如2,3-二氯-1,4-萘并醌、2-氧基-3-氯-1,4-萘并醌硫酸銅;五氯硝基苯;1,4-二氯-2,5-二甲氧基苯;5-甲基-s-三唑(3,4-b)苯并噻唑;2-(硫基氰基甲硫基)苯并噻唑;3-羥基-5-甲基異噁唑;N-2,3-二氯苯基四氯鄰胺甲醯苯甲酸;5-乙氧基-3-三氯甲基-1-2,4-噻二唑;2,4-二氯-6-(O-氯苯胺基)-1,3,5-三嗪;2,3-二氰基-1,4-二硫基蒽醌;8-喹啉酸銅、多抗黴素(polyoxine);有效黴素(validamycin);環己醯亞胺;甲基胂酸鐵;二異丙基-1,3-二硫戊環-2-依瑞丁(iridene)丙二酸酯;3-烯丙基氧基-1,2-苯并異噻唑-1,1-二氧化物;春日黴素(kasugamycin);殺稻瘟菌素S (Blasticidin S);4,5,6,7-四氯苯酞;3-(3,5-二氯苯基)-5-乙烯基-5-甲基噁唑嗪-2,4-二酮;N-(3,5-二氯苯基)-1,2-二甲基環丙烷-1,2-二羧基醯亞胺;二硫代羰基亞胺酸S-正丁基-5’-對第三丁基苄基-N-3-吡啶基酯;4-氯苯氧基-3,3-二甲基-1-(1H,1,3,4-三唑-1-基)-2-丁酮;D,L-N-(2,6-二甲基苯基)-N-(2’-甲氧基乙醯基)丙胺酸甲基酯;正丙基-N-[2-(2,4,6-三氯苯氧基)乙基]咪唑-1-甲醯胺;N-(3,5-二氯苯基)琥珀醯亞胺;四氯異酞腈;2-二甲基胺基-4-甲基-5-正丁基-6-羥基嘧啶;2,6-二氯-4-硝基苯胺;3-甲基-4-氯苯并噻唑-2-酮;1,2,5,6-四氫-4H-吡咯並[3,2,1-i,j]喹啉-2-酮;3’-異丙氧基-2-甲基苯醯替苯胺;1-[2-(2,4-二氯苯基)-4-乙基-1,3-二氧戊環-2-基甲基]-1H,1,2,4-三唑;1,2-苯并異噻唑啉-3-酮;鹼式氯化銅;鹼式硫酸銅;N’-二氯氟甲硫基-N,N-二甲基-N-苯基磺醯胺;乙基-N-(3-二甲基胺基丙基)硫代胺基甲酸酯鹽酸鹽;皮歐黴素(piomycin);二硫代碳酸S,S-6-甲基喹喏啉-2,3-二基酯;鋅及錳乃浦(manneb)之錯合物;雙(二甲基二硫代胺基甲酸)伸乙基雙(二硫代胺基甲酸)二鋅鹽及草甘膦;基於百菌清(chlorothalonil)之殺真菌劑;基於嗜毬果傘素(strobilurin)之殺真菌劑,例如嘧菌酯(azoxystrobin)、唑菌胺酯(pyraclostrobin)及肟菌酯(trifloxystrobin);及基於三唑之殺真菌劑,例如腈菌唑(myclobutanil)、丙環唑(propiconazole)、戊唑醇(tebuconazol)、氟醚唑(tetraconazole)或其組合。 在其他實施例中,試劑可係至少一種殺蟲劑。適宜殺蟲劑之非限制性實例包括磷殺蟲劑,例如硫代磷酸O,O-二乙基酯O-(2-異丙基-4-甲基-6-嘧啶基)酯、二硫代磷酸O,O-二甲基酯S-2-[(乙基硫基)乙基]酯、硫代磷酸O,O-二甲基酯O-(3-甲基-4-硝基苯基)酯、二硫代磷酸O,O-二甲基酯S-(N-甲基胺甲醯基甲基)酯、二硫代磷酸O,O-二甲基酯S-(N-甲基-N-甲醯基胺甲醯基甲基)酯、二硫代磷酸O,O-二甲基酯S-2-[(乙基硫基)乙基]酯、二硫代磷酸O,O-二乙基酯S-2-[(乙基硫基)乙基]酯、膦酸O,O-二甲基酯1-羥基-2,2,2-三氯乙基酯、硫代磷酸O,O-二乙基酯O-(5-苯基-3-異噁唑基)酯、硫代磷酸O,O-二甲基酯O-(2,5-二氯-4-溴苯基)酯、硫代磷酸O,O-二甲基酯O-(3-甲基-4-甲基巰基苯基)酯、硫代磷酸O-乙基酯O-對氰基苯基苯基酯、二硫代磷酸O,O-二甲基酯S-(1,2-二羰乙氧基乙基)酯、磷酸2-氯-(2,4,5-三氯苯基)乙烯基酯二甲基酯、磷酸2-氯-1-(2,4-二氯苯基)乙烯基酯二甲基酯、硫代磷酸O,O-二甲基酯O-對氰基苯基酯、磷酸2,2-二氯乙烯基酯二甲基酯、硫代磷酸O,O-二乙基酯O-2,4-二氯苯基酯、巰基苯基乙酸乙基酯、二硫代磷酸O,O-二甲基酯、二硫代磷酸S-[(6-氯-2-側氧基-3-苯并噁唑啉基)甲基]酯O,O-二乙基酯、磷酸2-氯-1-(2,4-二氯苯基)乙烯基酯二乙基酯、硫代磷酸O,O-二乙基酯O-(3-側氧基-2-苯基-2H-嗒嗪-6-基)酯、硫代磷酸O,O-二甲基酯S-(1-甲基-2-乙基亞磺醯基)-乙基酯、二硫代磷酸O,O-二甲基酯S-苯二甲醯亞胺基甲基酯、二硫代磷酸O,O-二乙基酯S-(N-乙氧基羰基-N-甲基胺甲醯基甲基)酯、二硫代磷酸O,O-二甲基酯S-[2-甲氧基-1,3,4-噻二唑-5-(4H)-酮基-(4)-甲基]酯、2-甲氧基-4H-1,3,2-苯并氧雜磷雜苯2-硫化物、硫代磷酸O,O-二乙基酯O-(3,5,6-三氯-2-吡啶基)酯、硫羰基苯膦酸O-乙基酯O-2,4-二氯苯基酯、二硫代磷酸S-[4,6-二胺基-s-三嗪-2-基-甲基]酯O,O-二甲基酯、硫代磷酸O-乙基酯O-對硝基苯基苯基酯、硫代磷醯胺酸O,S-二甲基酯N-乙醯基酯、硫代磷酸2-二乙基胺基-6-甲基嘧啶-4-基酯二乙基酯、硫代磷酸2-二乙基胺基-6-甲基嘧啶-4-基酯二甲基酯、硫代磷酸O,O-二乙基酯O-N-(甲基亞磺醯基)苯基酯、二硫代磷酸O-乙基S-丙基酯O-2,4-二氯苯基酯及順式-3-(二甲氧基膦氧基)N-甲基-順式-克羅酮(crotone)醯胺;胺基甲酸酯殺蟲劑,例如N-甲基胺基甲酸1-萘基酯、N-[甲基胺甲醯氧基]硫代乙醯亞胺酸S-甲基酯、甲基胺基甲酸間甲苯基酯、甲基胺基甲酸3,4-二甲苯基酯、甲基胺基甲酸3,5-二甲苯基酯、N-甲基胺基甲酸2-第二丁基苯基酯、甲基胺基甲酸2,3-二氫-2,2-二甲基-7-苯并呋喃基酯、N-甲基胺基甲酸2-異丙氧基苯基酯、1,3-雙(胺甲醯基硫基)-2-(N,N-二甲基胺基)丙烷鹽酸鹽及二甲基胺基甲酸2-二乙基胺基-6-甲基嘧啶-4-基酯;及其他殺蟲劑,例如N,N-二甲基N’-(2-甲基-4-氯苯基)甲脒鹽酸鹽、硫酸菸鹼、倍脈心(milbemycin)、6-甲基-2,3-喹喏啉二硫代環S,S-二硫代碳酸酯、二甲基丙烯酸2,4-二硝基-6-第二丁基苯基酯、1,1-雙(對氯苯基) 2,2,2-三氯乙醇、亞硫酸2-(對第三丁基苯氧基)異丙基酯-2’-氯乙基酯、氧化偶氮苯、二-(對氯苯基)-環丙基甲醇、二[三(2,2-二甲基-2-苯基乙基)錫]氧化物、1-(4-氯苯基)-3-(2,6-二氟苯甲醯基)脲、O,O-二異丙基二硫代磷酸S-三環己基錫或其組合。 在其他實施例中,試劑可係肥料。多種肥料適於納入組合物中。肥料可係單一營養肥料(N、P或K)、二元肥料(例如,NP、NK或PK)、NPK 肥料或多營養肥料(例如,可提供以下之一或多者:鈣、鎂、硫、銅、鐵、錳、鉬、鋅、硼、矽、鈷或釩)。肥料可為天然來源或合成來源,且肥料可係液體或固體,且可提供緩慢或受控釋放。 在替代實施例中,試劑可係一或多種溶劑、表面活性劑、黏合劑、填充劑、潤濕劑、增稠劑、泡沫控制劑、分散劑、崩解劑、pH調整劑、螯合劑、防腐劑或顏料,其實例詳細闡述於上文部分(III)(b)中。 (IV) 製備式 (I) 化合物之衍生物之方法
本揭示內容之另一態樣涵蓋製備式(I)化合物之衍生物之方法,其中該等衍生物包含低含量之硫酸根離子及硫酸氫鹽。(a) 式 (I) 化合物之金屬螯合物或金屬鹽
式(I)化合物可藉由使上文部分(I)中所揭示之調配物與金屬離子源接觸而轉化為金屬螯合物或金屬鹽。適宜金屬離子源包括金屬氧化物、金屬碳酸鹽或金屬氫氧化物。通常,金屬離子係選自鈣離子、鉻離子、鈷離子、銅離子、鐵離子、錳離子、銀離子、鈉離子、鋅離子或其組合。倘若金屬離子係銅、錳、鉻、鈷及鐵,則其較佳為二價。螯合物分子中式(I)化合物對金屬離子之比率通常可自1:1至3:1或更高變化。通常,金屬螯合物可包含1:1、2:1及3:1物質之混合物。在具體實施例中,螯合物分子中式(I)化合物對金屬離子之平均比率通常可自1.5:1至2.5:1變化。 通常,反應實質上係在大氣壓下進行,且反應物料加熱至90℃至130℃範圍內之溫度。在反應實質上完成之後,繼續加熱反應物料以產生實質上乾燥之產物。最終,游離水含量降低至以重量計約2%或更少,且產物物料轉變為自由流動之微粒固體。 自部分(I)中所詳述之調配物製備之式(I)化合物之金屬螯合物或金屬鹽具有低含量之硫酸根離子及硫酸氫鹽。舉例而言,式(I)化合物之金屬螯合物或金屬鹽包含約2700 ppm或更少之硫酸根離子及約500 ppm或更少之硫酸氫鹽。(b) 環狀二聚體衍生物
在一些實施例中,式(I)化合物可經受環化反應以形成環狀二聚體衍生物。製程包含使上文部分(I)中所詳述之調配物與酸觸媒在脫水條件下接觸以將式(I)化合物轉化為式(II)之環狀二聚體化合物:其中R1
及n係如上文部分(I)(a)中所定義。 (i) 酸觸媒
各種酸觸媒可用於環化反應中。在一些實施例中,酸觸媒可選自有機酸、無機酸及固體樹脂。例示性酸觸媒包括(但不限於)磷酸、乙酸、硼酸、鹽酸、三氟乙酸、甲磺酸、鄰甲苯磺酸、間甲苯磺酸及對甲苯磺酸、多磷酸、硫酸、甲苯磺酸、二甲苯磺酸、Dowex樹脂、Amberlyst樹脂、Zn塵及基於Sn之觸媒(例如Sn塵、氧化錫、氯化錫(II)、二月桂酸二丁基錫及辛酸亞錫)、二氧化鍺、三氧化銻、氧化鋅、氧化鐵(III)、氧化鋁、二氧化矽、二氧化鈦、其混合物及組合。在具體實施例中,酸觸媒可係對甲苯磺酸。 酸觸媒可以一系列比率添加至式(I)化合物。在一些態樣中,反應中所使用之觸媒之量可在式(I)化合物之0.0001 mol%至約5 mol%範圍內。在一些實施例中,反應中所使用之酸觸媒之量可係少於約5 mol%、少於約2 mol%或少於約1 mol%。在其他實施例中,反應中所使用之酸觸媒之量對於式(I)化合物可係約0.001 mol%、0.002 mol%、0.003 mol%、0.004 mol%、0.005 mol%、0.006 mol%、0.007 mol%、0.008 mol%、0.009 mol%或0.010 mol%。 (ii) 可選溶劑
反應可在溶劑存在下實施或反應可純淨地實施。在反應包括溶劑之情形下,溶劑之類型可端視反應物之身份而變化。因此,溶劑可係非極性溶劑、質子極性溶劑、非質子極性溶劑或其組合。適宜非極性溶劑之非限制性實例包括茴香醚、苯、乙酸丁酯、第三丁基甲醚、氯苯、氯仿、氯甲烷、環己烷、二氯甲烷、二氯乙烷、二-第三丁基醚、二甲醚、二乙二醇、二乙醚、二甘二甲醚、二異丙基醚、乙基第三丁基醚、環氧乙烷、氟苯、庚烷、己烷、甲基第三丁基醚、甲苯、二甲苯及其組合。適宜質子極性溶劑之實例包括(但不限於)水、醇(例如,甲醇、乙醇、異丙醇、正丙醇、異丁醇、正丁醇、第二丁醇、第三丁醇)、二醇(例如,丙二醇及諸如此類)、有機酸(例如,甲酸、乙酸等)、醯胺(例如,甲醯胺、乙醯胺及諸如此類)及以上任一者之組合。適宜非質子極性溶劑之非限制性實例包括丙酮、乙腈、二乙氧基甲烷、N,N-二甲基甲醯胺(DMF)、二甲亞碸(DMSO)、N,N-二甲基丙醯胺、1,3-二甲基-3,4,5,6-四氫-2(1H)-嘧啶酮(DMPU)、1,3-二甲基-2-咪唑啶酮(DMI)、1,2-二甲氧基乙烷(DME)、二甲氧基甲烷、雙(2-甲氧基乙基)醚、N,N-二甲基乙醯胺(DMAC)、N-甲基-2-吡咯啶酮(NMP)、1,4-二噁烷、乙酸乙酯、甲酸乙酯、甲醯胺、六氯丙酮、六甲基磷醯胺、乙酸甲酯、N-甲基乙醯胺、甲基乙基酮、甲基異丁基酮、N-甲基甲醯胺、二氯甲烷、甲氧基乙烷、嗎啉、硝基苯、硝基甲烷、丙腈、丙基乙酸酯、環丁碸、四甲脲、四氫呋喃(THF)、2-甲基四氫呋喃、四氫吡喃、三氯甲烷或其組合。在例示性實施例中,溶劑選自甲苯、二甲苯、茴香醚或其混合物。 溶劑對式(I)化合物之體積:質量比率可變化且將有所變化。通常,溶劑對式(I)化合物之體積:質量比率可在約1:1至約100:1範圍內。在各個實施例中,溶劑對式(I)化合物之體積:質量比率可在約1:1至約3:1、約3:1至約10:1、約10:1至約30:1或約30:1至約100:1範圍內。在一些實施例中,溶劑對式(I)化合物之體積:質量比率可係約30:1或約60:1。 (iii) 反應條件
一般而言,反應係在在脫水條件下進行以促進環化及環狀二聚體之形成。在某些實施例中,脫水可經由蒸餾來完成。舉例而言,反應可經受簡單蒸餾、分級蒸餾、共沸蒸餾、蒸汽蒸餾、真空蒸餾、使用迪安斯達克分離器(Dean Stark trap)或另一類似分離器之蒸餾、使用迪安斯達克或另一類似分離器之共沸蒸餾及諸如此類。在其他實施例中,脫水可經由乾燥試劑來完成,該乾燥試劑可包括分子篩、硫酸鈣、硫酸鎂、硫酸鈉、氫氧化鉀、碳酸鉀及諸如此類。 反應發生之溫度在不同實施例中及反應過程中可有所變化。在一個實施例中,反應可在約100℃至約200℃範圍內之溫度下進行。在另一實施例中,反應可在約100℃、110℃、120℃、130℃、140℃、150℃、160℃、170℃、180℃、190℃、200℃或該等值之任兩者之間且包括該等值之任兩者範圍內之溫度下進行。在另一實施例中,溫度可在約130℃至約150℃範圍內。在另一實施例中,溫度可在約110℃至約120℃範圍內。一般而言,反應係在大氣壓下進行,但在某些實施例中,反應亦可在大氣壓以上或以下進行。 反應之持續時間可變化且將有所變化。一般而言,可容許反應進行若干小時至若干天。然而,通常容許反應進行足夠時期直至反應完成為止,如藉由熟習此項技術者所熟知之方式測定。在此情況下,與反應開始時所存在之每一者之量相比,最終反應混合物含有顯著減少量之式(I)化合物及顯著增加量之式(II)化合物。在一些實施例中,可容許反應進行約1小時至約10小時範圍內之時期。在另一實施例中,可容許反應進行約1小時至約5小時範圍內之時期。在較佳實施例中,可容許反應進行約3小時至約5小時之時期。 式(II)化合物之產率可變化且將有所變化。一般而言,式(II)化合物之產率將係至少約15%、至少約20%、30%、至少約40%、至少約50%、至少約60%、至少約70%、至少約80%或至少約90%。 式(II)化合物可藉由包括以下之方式自反應混合物分離及/或純化:粒徑篩析層析、高效液相層析(HPLC)、離子交換層析、手性層析、其他類型之層析、沈澱、蒸餾或結晶。 自上文部分(I)中所詳述之調配物製備之式(II)化合物具有低含量之硫酸根離子及硫酸氫鹽。舉例而言,式(II)化合物包含約2700 ppm或更少之硫酸根離子及約500 ppm或更少之硫酸氫鹽。 (iv) 應用
式(II)之環狀二聚體化合物可用於各種應用中。適宜應用包括(但不限於)用作塑化劑、乳化劑、添加劑、處理助劑、營養劑、抗氧化劑、抗微生物劑、防蝕劑及飼料添加劑。(c) 酯衍生物
在其他實施例中,式(I)化合物可經歷酯化反應以形成酯衍生物。製程包含使上文部分(I)中所詳述之調配物與醇R3
OH接觸以將式(I)化合物轉化為式(III)之酯化合物:其中R1
、n及k係如上文部分(I)(a)中所定義,且R3
係烴基或經取代之烴基。 (i) 醇
在各個實施例中,R3
可係烷基、經取代之烷基、烯基、經取代之烯基、炔基、經取代之炔基、芳基或經取代之芳基。烷基、烯基及炔基可為直鏈、具支鏈或環狀。在一些實施例中,R3
可係C1
至C30
烷基,例如C1
、C2
、C3
、C4
、C5
、C6
、C7
、C8
、C9
、C10
、C11
、C12
、C13
、C14
、C15
、C16
、C17
、C18
、C19
、C20
、C21
、C22
、C24
、C26
、C28
或C30
烷基。在其他實施例中,R3
可係C1
至C30
烯基,例如C2
、C3
、C4
、C5
、C6
、C7
、C8
、C9
、C10
、C11
、C12
、C13
、C14
、C15
、C16
、C17
、C18
、C19
、C20
、C21
、C22
、C24
、C26
、C28
或C30
烯基。在其他實施例中,R3
可係經取代之烷基。舉例而言,經取代之烷基可包含一或多個醚鍵聯,例如聚醚(例如-(CH(R’)CH2
O)m
H或-(CH(R’)CH2
O)m
R”),其中R’係氫、烷基、經取代之烷基、羥基或胺基;R”係烷基、經取代之烷基、烯基或經取代之烯基;且m係1或更大之整數。在一些實施例中,聚醚可係聚(伸乙基氧化物)烷基。 在各個實施例中,R3
OH可係甲醇、乙醇、1-丙醇、2-丙醇、1-丁醇、2-丁醇、1-戊醇、2-戊醇、1-己醇、2-己醇、1-庚醇、2-庚醇、1-辛醇、2-辛醇、2-乙基己醇、3-乙基己醇、4-乙基己醇、1-甲基庚醇、2-甲基庚醇、3-乙基庚醇、4-甲基庚醇、1-壬醇、1-癸醇、1-十一醇、1-十二醇、1-十三醇、1-十四醇、1-十五醇、1-十六醇、順式-
9-十六烯-1-醇、1-正十七烷醇、1-十八烷醇、1-十九烷醇、1-二十烷醇、1-二十一烷醇、1-二十二烷醇、順式-
13-二十二烯-1-醇、1-二十四烷醇、1-二十六烷醇、1-二十八烷醇、1-三十烷醇或醇乙氧基化物。 與式(I)化合物接觸之R3
OH之量可變化且將有所變化。一般而言,式(I)化合物對R3
OH之莫耳:莫耳比率可在約1:0.1至約1:10範圍內。在各個實施例中,式(I)化合物對R3
OH之莫耳:莫耳比率可在約1:0.2至約1:8、約1:0.4至約1:6、約1:0.6至約1:5、約1:0.8至約1:4、約1:0.9至約1:3或約1:1至約1:2範圍內。 (ii) 觸媒
一般而言,反應係在觸媒存在下進行。觸媒可係化學觸媒,例如質子供體、有機金屬化合物(例如錫化合物)或業內已知之另一化學觸媒。或者,觸媒可係酶觸媒,例如脂肪酶。脂肪酶可催化酯鍵聯之形成(以及水解)。 在其中觸媒係質子供體之實施例中,在製程中可使用各種質子供體。適宜質子供體之非限制性實例包括酸式鹽(例如,硫酸氫鹽、硫酸氫鹽(hydrosulfate))、礦物質酸(例如,氫鹵化物(例如鹽酸、氫溴酸);鹵素含氧酸(例如次氯酸、氯酸、過氯酸、過碘酸;硫酸;硼酸;硝酸、磷酸等));磺酸(例如,甲磺酸、對甲苯磺酸);固體結合質子供體(例如,Amberlyst 15、Amberlyst 35及諸如此類);離子交換樹脂(例如,Amberlite、Amberjet、Dowex等);離聚物(例如,聚磺苯乙烯、Nafion、Hycar等);及具有酸性特徵之離子液體。 式(I)化合物對質子供體觸媒之莫耳:莫耳比率可端視質子供體之身份變化且將有所變化。一般而言,式(I)化合物對質子供體之莫耳:莫耳比率可在約1:0.005至約1:0.25範圍內。在一些實施例中,式(I)化合物對質子供體之莫耳:莫耳比率可係約1:0.01、約1:0.02、約1:0.04、約1:0.05、約1:0.06、約1:0.08、約1:0.10、約1:0.12、約1:0.14、約1:0.16、約1:0.18或約1:0.20。 (iii) 可選溶劑
酯化反應可在不存在溶劑或存在溶劑下進行。在其中存在溶劑之實施例中,溶劑之類型可端視反應物而變化。因此,溶劑可係非極性溶劑、極性溶劑或其組合。適宜非極性溶劑之非限制性實例包括苯、乙酸丁酯、第三丁基甲醚、氯苯、氯仿、氯甲烷、環己烷、二氯甲烷(DCM)、二氯乙烷、二-第三丁基醚、二甲醚、二乙二醇、二乙醚、二甘二甲醚、二異丙基醚、乙基第三丁基醚、環氧乙烷、氟苯、庚烷、己烷、甲基第三丁基醚、甲苯及其組合。適宜極性溶劑之非限制性實例包括丙酮、乙腈、二乙氧基甲烷、N,N-二甲基甲醯胺(DMF)、二甲亞碸(DMSO)、N,N-二甲基丙醯胺、1,3-二甲基-3,4,5,6-四氫-2(1H)-嘧啶酮(DMPU)、1,3-二甲基-2-咪唑啶酮(DMI)、1,2-二甲氧基乙烷(DME)、二甲氧基甲烷、雙(2-甲氧基乙基)醚、N,N-二甲基乙醯胺(DMAC)、N-甲基-2-吡咯啶酮(NMP)、1,4-二噁烷、乙酸乙酯、甲酸乙酯、甲醯胺、六氯丙酮、六甲基磷醯胺、乙酸甲酯、N-甲基乙醯胺、甲基乙基酮、甲基異丁基酮、N-甲基甲醯胺、二氯甲烷、甲氧基乙烷、嗎啉、硝基苯、硝基甲烷、丙腈、丙基乙酸酯、環丁碸、四甲脲、四氫呋喃(THF)、2-甲基四氫呋喃、四氫吡喃、三氯甲烷及其組合。在具體實施例中,溶劑可係甲苯。 溶劑對式(I)化合物之體積:質量比率可變化且將有所變化。通常,溶劑對式(I)化合物之體積:質量比率可在約1:1至約100:1範圍內。在各個實施例中,溶劑對式(I)化合物之體積:質量比率可在約1:1至約3:1、約3:1至約10:1、約10:1至約30:1或約30:1至約100:1範圍內。 (iv) 反應條件
反應可在約30℃至約200℃範圍內之溫度下進行。在某些實施例中,反應溫度可係約40℃、50℃、60℃、70℃、80℃、90℃、100℃、110℃、120℃、130℃、140℃或150℃。在具體實施例中,反應可在約80℃至約150℃之溫度下進行。 反應之持續時間可變化且將有所變化。一般而言,可容許反應進行約1小時至約24小時或更久。在一些實施例中,可容許反應過夜進行(或約12小時至約18小時)。然而,通常容許反應進行足夠時期直至反應進行至期望之完成度為止,如藉由熟習此項技術者所熟知之方式測定。在其中容許反應進行至完成之實施例中,「完全反應」通常意指與反應開始時所存在之每一者之量相比,最終反應混合物含有顯著減少量之式(I)化合物及顯著增加量之式(III)之酯化合物。 式(III)化合物可藉由業內已知之方式自反應混合物分離。適宜方式包括萃取、洗滌、沈澱、過濾、蒸餾、蒸發、乾燥、層析及其組合。式(III)化合物可包含單體、二聚體、三聚體及/或更長之寡聚物。在一些實施例中,可分離個別單體、二聚體等。 式(III)化合物之產率可變化且將有所變化。一般而言,化合物之產率將係至少約20%、至少約30%、至少約40%、至少約50%、至少約60%、至少約70%、至少約80%或至少約90%。 自上文部分(I)中所詳述之調配物製備之式(III)化合物具有低含量之硫酸根離子及硫酸氫鹽。舉例而言,式(III)化合物包含約2700 ppm或更少之硫酸根離子及約500 ppm或更少之硫酸氫鹽。 (v) 應用
在其中R3
係C1
至C12
烷基之實施例中,式(III)化合物具有溶劑性質,即,可溶解另一物質或另一物質可溶解於其中。因此,該等化合物可在各種應用及產品中用作溶劑,包括清潔及個人護理產品、農業應用、工業應用及塗料或漆料調配物。 在其中Z係SO且R3
係C8
至C30
烷基或烯基或R3
係聚(環氧乙烷)烷基之實施例中,式(III)化合物具有表面活性劑性質。具有表面活性劑性質之化合物可在多種消費者/工業產品及/或應用中用作清潔劑、淨化劑、潤濕劑、分散劑、乳化劑、發泡劑或消泡劑。(d) α 酯衍生物
在其他實施例中,式(I)化合物可經歷酯化反應,使得α碳處之羥基轉化為酯基。製程包含使上文部分(I)中所闡述之調配物與式R6
C(O)Y之醯鹵接觸以將式(I)化合物轉化為式(IV)化合物:其中R1
、k及n係如上文部分(I)(a)中所定義,R4
係脂肪族或經取代之脂肪族,且Y係鹵根離子。 (i) 醯鹵
在某些實施例中,R4
可係烷基、經取代之烷基、烯基、經取代之烯基、炔基或經取代之炔基。在一些實施例中,R4
可係C1
至C30
烷基、經取代之C1
至C30
烷基、C2
至C30
烯基或經取代之C2
至C30
烯基。烷基及烯基可係直鏈、具支鏈或環狀,且烯基可含有1至6個碳-碳雙鍵。在一些實施例中,R4
可係C6
至C24
烷基或C6
至C24
烯基。在具體實施例中,R4
可係C6
、C7
、C8
、C9
、C10
、C11
、C12
、C13
、C14
、C15
、C16
、C17
、C18
、C19
、C20
、C21
、C22
、C23
或C24
烷基或烯基。醯鹵之鹵根離子(Y)可係氯離子、溴離子、氟離子或碘離子。 醯鹵可源自天然脂肪酸(該天然脂肪酸可係直鏈、具支鏈、飽和或不飽和脂肪酸)。適宜醯鹵之非限制性實例包括己醯鹵、庚醯鹵、辛醯鹵、壬醯鹵、十一醯鹵、十二醯鹵(月桂醯鹵)、十三醯鹵、十四醯鹵(肉豆蔻醯鹵)、十五醯鹵、十六醯鹵(棕櫚醯鹵)、十七醯鹵、十八醯鹵(硬脂醯鹵)、十九醯鹵、花生醯鹵(arachidoyl halide)、山崳醯鹵(behenoyl halide)、木質醯鹵(lignoceroyl halide)、巴豆醯鹵(crotoyl halide)、肉豆蔻醯鹵(myristoloyl halide)、棕櫚醯鹵(palmitoloyl halide)、杉皮醯鹵(sapienoyl halide)、油醯鹵、反油醯鹵(elaidoyl halide)、十八烯醯鹵(vaccenoyl halide)、亞油醯鹵(linoloyl halide)、反亞油醯鹵(linoelaidoyl halide)、亞麻醯鹵(linolenoyl halide)、花生四烯醯鹵(arachidonoyl halide)、二十碳五烯醯鹵(eicosapentaenoyl halide)、瓢兒菜基鹵(erucoyl halide)及二十二碳六烯醯鹵(docosahexaenoyl halide)。 與式(I)化合物接觸之醯鹵之量可變化且將有所變化。一般而言,式(I)化合物對醯鹵R2
C(O)Y之莫耳:莫耳比率可在約1:0.2至約1:2.0範圍內。在一些實施例中,式(I)化合物對醯鹵之莫耳:莫耳比率可在約1:0.3至約1:1.5、約1:0.4至約1:1.2或約1:0.5至約1:1.0範圍內。 (ii) 可選觸媒及質子受體
酯化反應可在觸媒及質子受體存在下進行。在具體實施例中,觸媒可係親核觸媒。適宜親核觸媒之非限制性實例包括4-二甲基胺基吡啶(DMAP)、吡啶或其衍生物、咪唑或其衍生物、脒、異硫脲及胍。在具體實施例中,親核觸媒可係DMAP。通常,製程中使用催化量之觸媒。 適宜質子受體包括(但不限於)有機鹼,例如三乙胺、二異丙基乙胺、N-甲基嗎啉及其混合物;有機緩衝劑(例如,4-(2-羥基乙基)六氫吡嗪-1-乙磺酸(HEPES)、2 (4嗎啉基)乙磺酸(MES)、4-嗎啉丙烷磺酸(MOPS)、1,4-六氫吡嗪二乙磺酸(PIPES)、其鹽及/或混合物);硼酸鹽;二-及三-鹼式磷酸酯鹽;酸式碳酸鹽;氫氧化物鹽;碳酸鹽或其混合物。一般而言,式(I)化合物對質子受體之莫耳:莫耳比率在約1:0.1至約1:10範圍內。在各個實施例中,式(I)化合物對質子受體之莫耳:莫耳比率可在約1:0.5至約1:5、約1:1至約1:4或約1:1.8至約1:2.2範圍內。 (iii) 可選溶劑
反應可純淨地進行或在溶劑存在下進行。溶劑可係非極性溶劑、質子極性溶劑、非質子極性溶劑或其組合。適宜非極性溶劑之非限制性實例包括苯、乙酸丁酯、第三丁基甲醚、氯苯、氯仿、氯甲烷、環己烷、二氯甲烷(DCM)、二氯乙烷、二-第三丁基醚、二甲醚、二乙二醇、二乙醚、二甘二甲醚、二異丙基醚、乙基第三丁基醚、環氧乙烷、氟苯、庚烷、己烷、甲基第三丁基醚、甲苯及其組合。適宜質子極性溶劑包括(但不限於)醯胺,例如甲醯胺、乙醯胺及諸如此類。適宜非質子極性溶劑之非限制性實例包括丙酮、乙腈、二乙氧基甲烷、N,N-二甲基甲醯胺(DMF)、二甲亞碸(DMSO)、N,N-二甲基丙醯胺、1,3-二甲基-3,4,5,6-四氫-2(1H)-嘧啶酮(DMPU)、1,3-二甲基-2-咪唑啶酮(DMI)、1,2-二甲氧基乙烷(DME)、二甲氧基甲烷、雙(2-甲氧基乙基)醚、N,N-二甲基乙醯胺(DMAC)、N-甲基-2-吡咯啶酮(NMP)、1,4-二噁烷、乙酸乙酯、甲酸乙酯、甲醯胺、六氯丙酮、六甲基磷醯胺、乙酸甲酯、N-甲基乙醯胺、甲基乙基酮、甲基異丁基酮、N-甲基甲醯胺、二氯甲烷、甲氧基乙烷、嗎啉、硝基苯、硝基甲烷、丙腈、丙基乙酸酯、環丁碸、四甲脲、四氫呋喃(THF)、2-甲基四氫呋喃、四氫吡喃、三氯甲烷及其組合。在具體實施例中,溶劑可係二氯甲烷(DCM)。 溶劑對式(I)化合物之體積:質量比率可變化且將有所變化。通常,溶劑對式(I)化合物之體積:質量比率可在約1:1至約100:1範圍內。在各個實施例中,溶劑對式(I)化合物之體積:質量比率可在約1:1至約3:1、約3:1至約10:1、約10:1至約30:1或約30:1至約100:1範圍內。在較佳實施例中,溶劑對式(I)化合物之體積:質量比率可在約10:1至約30:1範圍內。 (iv) 反應條件
反應可在約-10℃至約80℃範圍內之溫度下進行。在某些實施例中,反應溫度可在約0℃至約20℃、約40℃至約40℃、約40℃至約60℃或約60℃至約80℃範圍內。在具體實施例中,反應可在約0℃下起始,且然後溫度可增加至約室溫。一般而言,反應將在大氣壓下進行。 反應之持續時間可變化且將有所變化。一般而言,可容許反應進行約1小時至約24小時或更久。在一些實施例中,可容許反應過夜進行(或約12小時至約18小時)。然而,通常容許反應進行足夠時期直至反應進行至期望之完成度為止,如藉由熟習此項技術者所熟知之方式測定。在其中容許反應進行至完成之實施例中,「完全反應」通常意指與反應開始時所存在之每一者之量相比,最終反應混合物含有顯著減少量之式(I)化合物及顯著增加量之式(IV)化合物。 式(IV)化合物可藉由業內已知之方式自反應混合物分離。適宜方式包括萃取、洗滌、沈澱、過濾、蒸餾、蒸發、乾燥、層析及其組合。式(IV)化合物可包含單體、二聚體、三聚體及/或更長之寡聚物。在一些實施例中,可分離個別單體、二聚體等。 式(IV)化合物之產率可變化且將有所變化。一般而言,化合物之產率可係至少約20%、至少約30%、至少約40%、至少約50%、至少約60%、至少約70%、至少約80%或至少約90%。 自上文部分(I)中所詳述之調配物製備之式(IV)化合物具有低含量之硫酸根離子及硫酸氫鹽。舉例而言,式(IV)化合物包含約2700 ppm或更少之硫酸根離子及約500 ppm或更少之硫酸氫鹽。 (v) 式 (IV) 化合物之羧酸鹽之製備
在一些實施例中,式(IV)化合物可與鹽接觸以形成羧酸鹽,其中陽離子與羧基之去質子化羥基錯合。適宜陽離子之實例包括銨及金屬(例如鈉、鉀、鋰、銫、鎂、鈣、錳、鈷、鎳、銅、鋅及鐵)。適宜鹽包括(但不限於)氫氧化物、氧化物、碳酸鹽、酸式碳酸鹽及諸如此類。在一些實施例中,鹽係游離的(例如,於溶液中)。在其他實施例中,鹽結合至樹脂(例如,離子交換樹脂)。 與式(IV)化合物接觸之鹽之量可變化且將有所變化。一般而言,式(IV)化合物對鹽之莫耳:莫耳比率可在約1:0.5至約1:2範圍內。在具體實施例中,式(IV)化合物對鹽之莫耳:莫耳比率可係約1:1。 反應可在溶劑存在下實施。適宜溶劑及比率詳細闡述於上文中。反應可在均相或異相反應條件下進行。反應溫度可有所變化,但通常係在約10℃至約50℃範圍內。反應之持續時間可有所變化,但通常係在約1小時至約1天範圍內。一般而言,容許反應進行直至反應完成或實質上完成為止,如藉由熟習此項技術者所熟知之方式測定。 (vi) 應用
在其中R4
係C6
至C24
烷基或C6
至C24
烯基之實施例中,式(IV)化合物或其羧酸鹽具有表面活性劑性質,且可在多種消費者/工業產品及/或應用中用作清潔劑、淨化劑、潤濕劑、分散劑、乳化劑、發泡劑、消泡劑或抗微生物劑。(e) 二酯衍生物
在其他實施例中,式(I)化合物可經歷兩個酯化反應以形成二酯衍生物。製程包含使上文部分(I)中所闡述之調配物與R3
OH接觸以形成酯,並使該酯與R4
C(O)Y接觸以形成式(V)之二酯:其中R1
、k及n係如上文部分(I)(a)中所定義,R3
係如上文部分(IV)(c)中所定義,且R4
及Y係如上文部分(IV)(d)中所定義。 第一酯化反應基本上如上文部分(IV)(c)中所闡述。第二酯化反應基本上如上文部分(IV)(d)中所闡述。式(V)化合物可包含單體、二聚體、三聚體及/或更長之寡聚物。 自上文部分(I)中所詳述之調配物製備之式(V)化合物具有低含量之硫酸根離子及硫酸氫鹽。舉例而言,式(V)化合物包含約2700 ppm或更少之硫酸根離子及約500 ppm或更少之硫酸氫鹽。 式(V)之二酯化合物具有塑化性質且可用於改良聚合物之撓性及/或抗衝擊性質。在一些實施例中,式(V)之二酯化合物可具有表面活性劑性質。因此,此化合物可在多種消費者/工業產品及/或應用中用作清潔劑、淨化劑、潤濕劑、分散劑、乳化劑、發泡劑或消泡劑。(f) 式 (I) 化合物之聚合物
在其他實施例中,式(I)化合物可經歷聚合反應以形成具有式(VI)之重複單元之聚合物。製程包含使上文部分(I)中所闡述之調配物與酸觸媒在脫水條件下接觸以形成混合物;及使該混合物經受減壓及升溫以形成聚合物,其中在起始調配物中式(VI)之重複單元之平均數大於k。式(VI)之重複單元:其中R1
及n係如上文部分(I)(a)中所定義。 (i) 酸觸媒
製程中所使用之酸觸媒可變化且將有所變化,且可選自業內已知之觸媒。在一些實施例中,酸觸媒可選自有機酸、無機酸或固體樹脂。例示性酸觸媒包括(但不限於)硼酸、鹽酸、三氟乙酸、甲磺酸、鄰甲苯磺酸、間甲苯磺酸及對甲苯磺酸、硫酸、磷酸、甲苯磺酸、二甲苯磺酸、Dowex樹脂、Amberlyst樹脂、Zn塵及基於Sn之觸媒(例如Sn塵、氧化錫、氯化錫(II)、二月桂酸二丁基錫及辛酸亞錫)、二氧化鍺、三氧化銻、氧化鋅、氧化鐵(III)、氧化鋁、二氧化矽、二氧化鈦、其混合物及組合。在具體實施例中,酸觸媒可係辛酸亞錫。 酸觸媒可以一系列比率添加至式(I)化合物。在一些態樣中,所添加觸媒之量可在式(I)化合物之約0.01 wt %至約1 wt %或更高之範圍內。在一些實施例中,酸觸媒可以式(I)化合物之約0.1 wt %至約0.5 wt %範圍內之量添加。在其他實施例中,酸觸媒係以式(I)化合物之約0.1 wt %、0.2 wt %、0.3 wt %、0.4 wt %或0.5 wt %之量添加。 (ii) 可選溶劑
製程可在溶劑存在下實施,或可在溶劑不存在下進行。溶劑可係非極性溶劑、質子極性溶劑、非質子極性溶劑或其組合。適宜非極性溶劑之非限制性實例包括茴香醚、苯、乙酸丁酯、第三丁基甲醚、氯苯、氯仿、氯甲烷、環己烷、二氯甲烷、二氯乙烷、二-第三丁基醚、二甲醚、二乙二醇、二乙醚、二甘二甲醚、二異丙基醚、乙基第三丁基醚、環氧乙烷、氟苯、庚烷、己烷、甲基第三丁基醚、甲苯、二甲苯及其組合。適宜質子極性溶劑之實例包括(但不限於)水、醇(例如,甲醇、乙醇、異丙醇、正丙醇、異丁醇、正丁醇、第二丁醇、第三丁醇)、二醇(例如,丙二醇及諸如此類)、有機酸(例如,甲酸、乙酸等)、醯胺(例如,甲醯胺、乙醯胺及諸如此類)及以上任一者之組合。適宜非質子極性溶劑之非限制性實例包括丙酮、乙腈、二乙氧基甲烷、N,N-二甲基甲醯胺(DMF)、二甲亞碸(DMSO)、N,N-二甲基丙醯胺、1,3-二甲基-3,4,5,6-四氫-2(1H)-嘧啶酮(DMPU)、1,3-二甲基-2-咪唑啶酮(DMI)、1,2-二甲氧基乙烷(DME)、二甲氧基甲烷、雙(2-甲氧基乙基)醚、N,N-二甲基乙醯胺(DMAC)、N-甲基-2-吡咯啶酮(NMP)、1,4-二噁烷、乙酸乙酯、甲酸乙酯、甲醯胺、六氯丙酮、六甲基磷醯胺、乙酸甲酯、N-甲基乙醯胺、甲基乙基酮、甲基異丁基酮、N-甲基甲醯胺、二氯甲烷、甲氧基乙烷、嗎啉、硝基苯、硝基甲烷、丙腈、丙基乙酸酯、環丁碸、四甲脲、四氫呋喃(THF)、2-甲基四氫呋喃、四氫吡喃、三氯甲烷及其組合。在另一實施例中,溶劑可係共沸蒸餾溶劑。在具體實施例中,溶劑可係茴香醚、甲苯或二甲苯。 溶劑對式(I)化合物之重量:重量比率可變化且將有所變化。通常,溶劑對式(I)化合物之重量:重量比率可在約1:1至約20:1範圍內。在各個實施例中,溶劑對式(I)化合物之重量:重量比率可係約2:1、3:1、3.5:1、4.0:1、4.5:1、5.0:1、5.5:1、6.0:1、6.5:1. 7.0:1、7.5:1、8:1、8:1或10:1。 (iii) 可選試劑
在一些實施例中,反應混合物可補充至少一種額外單體,使得產生共聚物。適宜單體之非限制性實例包括二元酸、二醇、羥基酸、丙烯酸酯、胺基丙烯酸酯、琥珀酸伸烷基酯、草酸伸烷基酯、酸酐、芳基化物、碳酸酯、纖維素、己內酯、氰基丙烯酸酯、環醚、二氫吡喃、二噁烷、二氧雜環己酮、醚醚酮、乙二醇、酯、延胡索酸酯、羥基烷酸酯、羥基酯、醯亞胺、縮酮、乳酸交酯、內酯、甲基丙烯酸酯、甲基烯烴、原酸酯、膦嗪、苯乙烯、對苯二甲酸酯、四氫呋喃、三亞甲基碳酸酯、胺基甲酸酯、乙酸乙烯酯、乙烯基酮、乙烯基鹵化物、前述任一者之衍生物或其混合物。 式(I)化合物對一或多種額外單體之重量比可端視所期望之共聚物性質而變化。在一些態樣中,式(I)化合物對一或多種額外單體之重量比可在約99.9:0.1至約0.1:99.9範圍內。在各個實施例中,式(I)化合物對一或多種額外單體之重量比可係約99:1、95:5、90:10、85:15、80:20、75:25、70:30、65:35、60:40、55:45、50:50、45:55、40:60、35:65、30:70、25:75、20:80、15:85、10:90、5:95或1:99重量%。 在其他實施例中,可向反應混合物添加鏈延長劑。鏈延長劑可係選自業內已知之彼等。適宜鏈延長劑包括(但不限於)己二酸、琥珀酸、檸檬酸、異氰酸酯(例如1,6-六亞甲基二異氰酸酯)、噁唑啉延長劑(例如2,2-雙(2-噁唑啉)琥珀酸酐)及聚乙二醇(PEG)。在一些實施例中,鏈延長劑可以約0.01 wt%至約10 wt %範圍內之量添加至式(I)化合物。 (iv) 反應條件 - 製程之第一步
使反應混合物經受脫水以促進聚合物之形成。在某些實施例中,脫水可經由蒸餾來完成。舉例而言,反應混合物可經受簡單蒸餾、分級蒸餾、共沸蒸餾、使用迪安斯達克或另一類似分離器之共沸蒸餾、蒸汽蒸餾、真空蒸餾、使用迪安斯達克分離器或另一類似分離器之蒸餾及諸如此類。在一個實施例中,反應混合物經受共沸蒸餾。 製程之第一步可在約100℃至約200℃範圍內之溫度下進行。在一些態樣中,第一步可在約100℃、110℃、120℃、130℃、140℃、150℃、160℃、170℃、180℃、190℃、200℃或該等值之任兩者之間且包括該等值之任兩者範圍內之溫度下進行。在具體實施例中,在製程之整個此步驟中可將溫度維持在約120℃至約150℃下。 一般而言,製程之此步驟係在減壓下進行。在一些實施例中,壓力可降低至約100 mmHg至約300 mmHg之壓力。在其他實施例中,壓力可降低至約200 mmHg。在替代實施例中,製程可在大氣壓(即,760 mmHg)下開始,且然後可在一段時期之後將壓力降低。在其他實施例中,製程之此步驟可在惰性氛圍下進行,例如在氬或氮氛圍中。 製程之此步驟之持續時間可變化且將有所變化。一般而言,第一步可容許進行約2小時至約20小時。在一些態樣中,反應進展可藉由量測製程期間所去除之水之量來監測。 (v) 反應條件 - 製程之第二步
製程之第二步包含使反應混合物經受升溫及減壓以形成包含式(VI)之重複單元之聚合物。 在各個實施例中,製程之此步驟可在約140℃至約250℃範圍內之溫度下實施。在其他實施例中,反應可在約140℃、150℃、160℃、170℃、180℃、190℃、200℃、210℃、220℃、230℃、240℃、250℃或該等值之任兩者之間且包括該等值之任兩者範圍內之溫度下進行。在具體實施例中,溫度可係約170℃。 在一些實施例中,壓力可維持在近似於第一步之壓力,且可在約100 mmHg至約300 mmHg範圍內。在其他實施例中,壓力可降低至0 mmHg至約50 mmHg。在其他實施例中,壓力可降低至約0 mmHg、10 mmHg、20 mmHg、30 mmHg、40 mmHg或50 mmHg。在具體實施例中,壓力可降低至約30 mmHg。在一些實施例中,製程之第二步可在類似於第一步中所闡述之彼等之脫水條件下進行。 第二步之持續時間可變化且將有所變化。一般而言,可容許反應進行約2小時至約10小時,或更佳約3小時至約5小時。然而,通常容許反應進行足夠時期直至反應完成為止,如藉由熟習此項技術者所熟知之方式測定。在此情況下,「完全反應」通常意指與反應開始時所存在之每一者之量相比,最終反應混合物含有顯著減少量之式(I)化合物及顯著增加量之包含式(IV)之重複單元之聚合物。在一些態樣中,反應完全性可藉由監測製程中所去除之水之量並與水之理論量比較來量測。 藉由此製程所產生之聚合物之產率可係至少約30%、至少約40%、至少約50%、至少約60%、至少約70%、至少約80%或至少約90%。在一些實施例中,所得均聚物或共聚物可具有較低含量之游離單體或二聚體。游離單體及二聚體之百分比可在所產生之總均聚物或共聚物之約0%至約40%範圍內。在一些實施例中,游離單體及二聚體可佔總組合物之30%以下、或總組合物之20%以下、或總組合物之10%以下。在一些實施例中,游離單體百分比可係小於約10%、小於約9%、小於約8%、小於約7%、小於約6%、小於約5%、小於約4%、小於約3%、小於約2%或小於約1%。 自上文部分(I)中所詳述之調配物製備之包含式(VI)之重複單元之聚合物具有低含量之硫酸根離子及硫酸氫鹽。舉例而言,該等聚合物包含以重量計約2700 ppm或更少之硫酸根離子及約500 ppm或更少之硫酸氫鹽。 聚合物可原樣使用或聚合物可視情況藉由包括以下之方式來純化:粒徑篩析層析(SEC)、高效液相層析(HPLC)、離子交換層析、其他類型之層析、沈澱或結晶。 聚合物之平均分子量可端視且將端視反應物及反應條件而變化。一般而言,聚合物之平均分子量可為約數百直至約數萬。 (vi) 應用
包含式(VI)之重複單元之聚合物(或共聚物)在工業或農業應用中具有各種用途。有利地,該等聚合物係可生物降解及生物相容聚合物。(g) 亞碸或碸衍生物
上文所詳述之任一化合物可經歷一或多個氧化反應以將硫轉化為亞碸或碸。 在此製程中可使用各種氧化劑。適宜氧化劑之非限制性實例包括過氧酸(例如,氯過氧苯甲酸、過乙酸、過氧硫酸)、過氧化氫、過氯酸鹽、亞氯酸鹽、次氯酸鹽、氯酸鹽、硫酸、過硫酸、六價鉻化合物、過錳酸鹽化合物、過硼酸鈉、硝酸、硝酸鹽化合物、金屬氧化劑(例如,苯硒酸、四乙酸鉛、四氧化鋨、磷鉬酸水合物、氯鉻酸吡啶鎓鹽、重鉻酸吡啶鎓鹽、重鉻酸喹啉鎓鹽及諸如此類)及其組合。在較佳實施例中,氧化劑可係間氯過氧苯甲酸或過氧化氫。 式(I)、(II)、(III)、(IV)、(V)或(VI)化合物對氧化劑之莫耳:莫耳比率可變化且將有所變化。一般而言,化合物對氧化劑之莫耳:莫耳比率可在約1:0.1至約1:20、約1:0.2至約1:10、約1:0.5至約1:5或約1:1至約1:3範圍內。 氧化反應可在溶劑存在下實施。溶劑可係非極性溶劑、質子溶劑或非質子溶劑,此取決於反應物之本性。適宜溶劑詳細闡述於上文中。溶劑對式(I)、(II)、(III)、(IV)、(V)或(VI)化合物之體積:質量比率可變化且將有所變化。通常,溶劑對化合物之體積:質量比率可在約1:1至約60:1範圍內。在各個實施例中,溶劑對化合物之體積:質量比率可在約4:1至約40:1範圍內。 氧化反應可在約-10℃至約50℃範圍內之溫度下進行。在某些實施例中,反應溫度可係約0℃、約10℃、約20℃、約25℃或約30℃。在一個實施例中,可容許反應在約0℃下進行。在另一實施例中,可容許反應在0℃下進行第一段時期且在室溫下進行第二段時期。在另一實施例中,反應可在室溫下進行。通常,反應將在大氣壓下進行。 反應之持續時間可變化且將有所變化。一般而言,可容許反應進行若干小時至若干天。然而,通常可容許反應進行足夠時期直至反應完成或實質上完成為止,如藉由熟習此項技術者所熟知之方式測定。定義
在介紹本文所述實施例之要素時,冠詞「一(a、an)」、「該(the)」及「該(said)」意欲意指存在該等要素中之一或多者。術語「包含(comprising)」、「包括(including)」及「具有(having)」意欲具有包括性且意指除所列示要素以外亦可存在其他要素。 如本文中單獨或作為另一基團之一部分所使用之術語「醯基」表示藉由自有機羧酸之基團COOH去除羥基形成之部分(例如RC(O)-),其中R係R1
、R1
O-、R1
R2
N-或R1
S-,R1
係烴基、雜取代烴基或雜環,且R2
係氫、烴基或經取代之烴基。 如本文中單獨或作為另一基團之一部分所使用之術語「醯氧基」表示藉助氧鍵聯(O)鍵結之如上文所述之醯基(例如RC(O)O-),其中R係如結合術語「醯基」所定義。 如本文中所使用,術語「脂肪族」係指其中碳原子以開鏈鏈接之烴基,即直鏈或具支鏈但非環狀。視情況經取代之烷基、烯基及炔基係脂肪族基團。 如本文中所使用之術語「烷基」描述主鏈中含有1至30個碳原子之基團。其可為直鏈或具支鏈或環狀且包括甲基、乙基、丙基、異丙基、丁基、己基及諸如此類。 如本文中所使用之術語「烯基」描述主鏈中含有2至30個碳原子且進一步包含至少一個碳-碳雙鍵之基團。其可為直鏈或具支鏈或環狀且包括乙烯基、丙烯基、異丙烯基、丁烯基、異丁烯基、己烯基及諸如此類。 如本文中所使用之術語「烷氧化物」或「烷氧基」係醇之共軛鹼。醇可為直鏈、具支鏈、環狀,且包括芳基氧基化合物。 如本文中所使用之術語「炔基」描述主鏈中含有2至30個碳原子且進一步包含至少一個碳-碳三鍵之基團。其可為直鏈或具支鏈且包括乙炔基、丙炔基、丁炔基、異丁炔基、己炔基及諸如此類。 如本文中所使用之術語「醯胺」描述包含羰基-氮鍵聯之化合物。 術語「胺基醯基」係指胺基酸殘基。 如本文中單獨或作為另一基團之一部分所使用之術語「芳香族」表示視情況經取代之包含非定域電子之同素或雜環狀共軛平面環或環系統。該等芳香族基團較佳為在環部分中含有5至14個原子之單環狀(例如呋喃或苯)、雙環狀或三環狀基團。術語「芳香族」涵蓋下文中所定義之「芳基」基團。 如本文中單獨或作為另一基團之一部分所使用之術語「芳基」表示視情況經取代之同素環狀芳香族基團,較佳在環部分中含有6至10個碳之單環狀或雙環狀基團,例如苯基、聯苯、萘基、經取代之苯基、經取代之聯苯或經取代之萘基。 如本文中所使用,術語「發色體」係指可見色彩或有色雜質,其可藉由使用分光光度色度儀在可見光範圍內使用大約400-700 nm之波長來量化。 如本文中單獨或作為另一基團之一部分所使用之術語「鹵素」或「鹵基」係指氯、溴、氟及碘。 術語「雜原子」係指除碳及氫以外之原子。 如本文中單獨或作為另一基團之一部分所使用之術語「雜芳香族」表示在至少一個環中具有至少一個雜原子且較佳在每一環中具有5或6個原子之視情況經取代之芳香族基團。雜芳香族基團較佳在環中具有1或2個氧原子及/或1至4個氮原子,且藉助碳鍵結至分子之其餘部分。例示性基團包括呋喃基、苯并呋喃基、噁唑基、異噁唑基、噁二唑基、苯并噁唑基、苯并噁二唑基、吡咯基、吡唑基、咪唑基、三唑基、四唑基、吡啶基、嘧啶基、吡嗪基、嗒嗪基、六氫吡啶基、吲哚基、異吲哚基、吲嗪基、苯并咪唑基、吲唑基、苯并三唑基、四唑并嗒嗪基、咔唑基、嘌呤基、喹啉基、異喹啉基、咪唑并吡啶基及諸如此類。例示性取代基包括以下基團中之一或多者:烴基、經取代之烴基、烷基、烷氧基、醯基、醯氧基、烯基、烯氧基、芳基、芳基氧基、胺基、醯胺基、縮醛、胺甲醯基、碳環、氰基、酯、醚、鹵素、雜環、羥基、酮基、縮酮、二氧磷基、硝基及硫基。 如本文中單獨或作為另一基團之一部分所使用之術語「雜環基(heterocyclo)」或「雜環(heterocyclic)」係表示在至少一個環中具有至少一個雜原子、且較佳在每一環中具有5或6個原子之視情況經取代、完全飽和或不飽和、單環或二環、芳香族或非芳香族基團。雜環基團較佳在環中具有1或2個氧原子及/或1至4個氮原子,且藉助碳或雜原子鍵結至分子之其餘部分。例示性雜環基團包括如上文所闡述之雜芳香族基。例示性取代基包括以下基團中之一或多者:烴基、經取代之烴基、烷基、烷氧基、醯基、醯氧基、烯基、烯氧基、芳基、芳基氧基、胺基、醯胺基、縮醛、胺甲醯基、碳環、氰基、酯、醚、鹵素、雜環、羥基、酮基、縮酮、二氧磷基、硝基及硫基。 如本文中所使用之術語「烴」及「烴基」描述僅由元素碳及氫組成之有機化合物或基團。該等部分包括烷基、烯基、炔基及芳基部分。該等部分亦包括經其他脂肪族或環狀烴基取代之烷基、烯基、炔基及芳基部分,例如烷芳基、烯芳基及炔芳基。其可係直鏈、具支鏈或環狀。 如本文中所使用之術語「保護基團」表示能夠保護官能基(例如,醇或胺)之基團,其中可在採用保護之反應之後去除保護基團,而不干擾分子之其餘部分。適宜醇保護基團之非限制性實例包括乙醯基(Ac)、苯甲醯基(Bz)、苄基(Bn,Bnl)、β-甲氧基乙氧基甲醚(MEM)、二甲氧基三苯甲基(DMT)、甲氧基甲醚(MOM)、甲氧基三苯甲基(MMT)、對甲氧基苄基醚(PMB)、甲硫基甲醚、特戊醯基(Piv)、四氫吡喃基(THP)、三苯甲基(三苯基甲基,Tr)、矽基醚(例如,三甲基矽基(TMS)、第三丁基二甲基矽基(TBDMS)、三異丙基矽基氧基甲基(TOM)及三異丙基矽基(TIPS)醚)、甲醚及乙氧基乙基醚(EE)及諸如此類。適宜胺保護基團包括(但不限於)苄氧羰基(Cbz);對甲氧基苄基羰基(Moz或MeOZ)、第三丁基氧基羰基(BOC)、9-茀基甲基氧基羰基(FMOC)、乙醯基(Ac)、苯甲醯基(Bz)、苄基(Bn)、胺基甲酸酯、對甲氧基苄基(PMB)、3,4-二甲氧基苄基(DMPM)、對甲氧基苯基(PMP)、甲苯磺醯基(Ts)及其他磺醯胺(例如,Nosyl & Nps)及諸如此類。各種保護基團及其合成可參見「Protective Groups in Organic Synthesis」,T.W. Greene及P.G.M. Wuts,John Wiley & Sons, 2006。 如本文中所使用,術語「鹽雜質」係指硫酸氫鹽、硫酸根及其他陰離子及/或銨以及其他陽離子。 本文中所闡述之「經取代之烴基」部分係經至少一個除碳以外之原子取代之烴基部分,其包括其中碳鏈原子經雜原子(例如氮、氧、矽、磷、硼或鹵素原子)取代之部分及其中碳鏈包含其他取代基之部分。該等取代基包括烷基、烷氧基、醯基、醯氧基、烯基、烯氧基、芳基、芳基氧基、胺基、醯胺基、縮醛、胺甲醯基、碳環、氰基、酯、醚、鹵素、雜環、羥基、酮基、縮酮、二氧磷基、硝基及硫基。 已對本發明進行詳細闡述,顯而易見在不背離隨附申請專利範圍中所定義之本發明範圍下可進行修改及改變。實例
以下實例說明本揭示內容之各個實施例。 實例 1 :高純度 HMTBA 樣品之製備
用作起始材料及對照之高純度HMTBA之製備係藉由在80℃下於水中水解HMTBA之環狀二聚體來達成,如以下反應方案中所示:去除反應混合物中之水直至水濃度為大約11%為止。HPLC顯示所得HMTBA產物(HMTBA-hp)含有單體、二聚體、三聚體及少量四聚體(n = 1-4)。每一組分在210 nm處之面積%分佈示於表1中。
進一步分析揭示所得HMTBA-hp含有35 ppm之硫酸根離子且APHA值為54。此調配物用作起始材料以研究在升高溫度下各種硫酸鹽及硫酸氫鹽濃度之效應。 已知更高之溫度除了增加寡聚物含量以外亦引起HMTBA調配物變暗。實例2及3檢查在140℃下加熱及寡聚化期間增加硫酸或硫酸氫銨之濃度對所得HMTBA調配物之色彩之效應。該等實例提供加速測試以評價HMTBA調配物之色彩及氣味穩定性。 實例 2 :硫酸濃度對 HMTBA 調配物之色彩之效應
將大約22.5-30.5克之HMTBA-hp稱重至配備有攪拌棒之40 ml透明玻璃小瓶中。將量測量之硫酸溶液(9.8 wt/wt%)添加至每一小瓶以達成期望之硫酸根含量,如表2中所示。取出等分試樣(0.3克)並用去離子水(1.7克)稀釋,並使用pH計在室溫下量測每一(15%)溶液之pH。將五種溶液之每一者之等分試樣(6.5 g)溶解於四氫呋喃(6.5 g)中以製備50 wt%溶液,並藉由標準ASTM方法D1209利用Lovibond PFXi 195 Series儀器量測APHA色彩值。每一樣品以一式三份量測,且平均值報告於表2中。 小瓶用隔膜覆蓋並加熱至140℃,同時在氮下在Chemglass PieBlock反應器站中以500 rpm攪拌。在溶液達到140℃之後量測經過時間。在140℃下12小時之後,將小瓶快速冷卻至環境溫度。將五種反應之每一者之等分試樣(6.5 g)溶解於四氫呋喃(6.5 g)中以製備50 wt%溶液,並如上文所詳述進行APHA色彩分析。將剩餘樣品自小瓶轉移至經配衡20 mL玻璃頂空小瓶中並加熱至140℃,並在氮下以500 rpm再攪拌12小時。然後將樣品快速冷卻至環境溫度,並藉由上文所闡述者測定及每一樣品之APHA色彩。APHA色彩值隨時間之變化示於表2及圖1中。樣品1 (即,HMTBA-hp)及樣品2 (即,具有0.1%硫酸之HMTBA-hp)二者之APHA色彩值甚至在140℃下加熱24小時之後仍保持較低。
藉由HPLC分析加熱24小時之後樣品之寡聚物組成。每一組分在210 nm處之面積%分佈報告於表3中。
總之,在140℃下24小時之後,等於或小於0.1% (按照硫酸根量測)之硫酸濃度不會產生顯著著色(APHA <250)之HMTBA調配物。大於0.27%之硫酸根濃度產生深色HMTBA調配物(APHA >500)。正如預期,所有HMTBA樣品在加熱後普遍寡聚化(n>5) (參見表3)。然而,此實例指示寡聚化本身並不有害影響樣品色彩。樣品色彩僅受所存在之硫酸之量影響。 實例 3 :所添加之硫酸氫鹽對 HMTBA 調配物之色彩之效應
將大約22.5-30.5克之HMTBA-hp稱重至配備有攪拌棒之五個40 ml透明玻璃小瓶中。將硫酸氫銨溶液(5 wt/wt%)添加至四個樣品以達成期望之硫酸根含量(參見表4)。取出等分試樣(0.3克)並用去離子水(1.7克)稀釋,並在室溫下使用pH計量測每一溶液之pH。藉由比色法測定每一樣品之初始APHA色彩值,基本上如實例2中所述。將剩餘樣品加蓋並加熱至140℃且在氮下以500 rpm攪拌12小時或24小時,並基本上如上文實例2中所闡述測定APHA色彩值。色彩變化示於表4及圖2中。
藉由HPLC分析加熱24小時之後樣品之寡聚物組成。報告每一組分在210 nm處之面積%分佈(參見表5)。
總之,在140℃下24小時之後,等於或小於0.01%之硫酸氫根濃度(來自硫酸氫銨)不會產生顯著著色(APHA <250)之HMTBA調配物。大於0.27%之硫酸根濃度產生深色HMTBA樣品(APHA >500)。數據亦顯示所有反應混合物寡聚化(n>5)至相同程度。該等數據明確指示,寡聚化本身並不有害影響樣品色彩。樣品色彩僅受所存在之硫酸氫銨之量影響。 實例 4 :藉由與吸附劑接觸自市售 HMTBA 來源產生特用 HMTBA 產物或調配物之方法
脫色調配物(HMTBA OP)係自HMTBA動物補充劑(88% HMTBA)藉由以下來製備:用水稀釋以提供具有期望HMTBA濃度之水溶液,並使所得溶液通過活性木炭管柱以去除發色體(參見圖3A中所圖解之方法)。自該經脫色之溶液去除水以提供 HMTBA OP。此製程不去除硫酸氫鹽或硫酸。 實例 5 :藉由溶劑萃取自市售 HMTBA 來源產生特用 HMTBA 產物或調配物之方法
特用HMTB調配物(HMTBA P5)係自HMTBA動物補充劑(88% HMTBA)使用圖3B中所圖解之溶劑萃取製程來製備。為此,將HMTBA動物補充劑用水稀釋以提供具有期望HMTBA濃度之水溶液並使所得溶液通過活性木炭管柱以去除有色體。用甲基異丁基酮(MIBK)萃取經脫色之HMTBA溶液。為此,使1 g之HMTBA與0.75 g之MIBK接觸,並分離各相。有機相含有HMTBA,而硫酸及硫酸氫鹽保留在水相中。然後將MIBK自有機相蒸餾出以提供HMTBA P5樣品。 實例 6 :藉由離子交換製程自市售 HMTBA 來源產生特用 HMTBA 產物或調配物之方法
特用HMTBA調配物(HMTBA IEX)係自HMTBA動物補充劑(88% HMTBA)使用圖3C中所圖解之離子交換製程來製備。將HMTBA動物補充劑(88% HMTBA)用水稀釋以提供具有期望HMTBA濃度之水溶液,並使所得溶液通過活性木炭管柱以去除有色體。然後使該經脫色之HMTBA溶液通過強酸陽離子交換管柱,之後弱鹼陰離子交換樹脂,並將最終水溶液濃縮以提供HMTBA IEX。 表6顯示藉由實例4及5中所闡述之製程獲得之HMTB調配物與起始HMTBA動物補充劑之比較。 實例 7 :市售 HMTBA 來源之稀釋及過濾
將HMTBA動物補充劑(88% HMTBA)用水稀釋以提供包含15% HMTBA之水溶液。將15% HMTBA之水溶液充分混合並使其在室溫下靜置18-24小時。在此期間形成油性發色體。藉助CELITE®過濾包含油性發色體之水溶液以去除油性發色體。 可使15% HMTBA之經過濾水溶液與活性木炭接觸,如實例4中所闡述,並藉由如實例5中所闡述之溶劑萃取或如實例6中所闡述之離子交換進行進一步純化。
圖1
圖解說明在添加硫酸並加熱至140℃之HMTBA樣品中APHA色彩值隨時間之變化。所繪製的係在140℃下APHA色彩值隨小時之變化。 圖2
顯示在添加硫酸氫銨並加熱至140℃之HMTBA樣品中APHA色彩值隨時間之變化。所繪製的係在140℃下APHA色彩值隨小時之變化。 圖3A
圖解自HMTBA去除有色雜質(或發色體)之製程。 圖3B
呈現製備特用HMTBA之溶劑萃取製程之圖表。 圖3C
顯示用於製備特用HMTBA之離子交換製程之圖表。
Claims (24)
- 如請求項1之調配物,其中R1 係甲基且n係2。
- 如請求項1之調配物,其具有200或更小之美國公共衛生協會(American Public Health Association,APHA)色彩值。
- 如請求項1之調配物,其在140℃下加熱長達約12小時之後具有500或更小之APHA色彩值。
- 如請求項1之調配物,其包含以重量計約500 ppm或更少之硫酸氫根離子。
- 如請求項1之調配物,其包含以重量計15%之水且pH值為至少1.3。
- 如請求項7之調配物,其中R1 係甲基且n係2。
- 如請求項7之調配物,其中在140℃下加熱長達約12小時之後該APHA色彩值為500或更小。
- 如請求項7之調配物,其包含以重量計約2700 ppm或更少之硫酸根離子。
- 如請求項7之調配物,其包含以重量計約500 ppm或更少之硫酸氫根離子。
- 如請求項7之調配物,其包含以重量計15%之水且pH值為至少1.3。
- 一種營養組合物,其包含如請求項1或請求項7之調配物及至少一種選自營養劑、生物活性劑、賦形劑或其組合之試劑。
- 如請求項13之營養組合物,其中該營養劑係選自碳水化合物源、蛋白質源、脂質源或其組合,且該生物活性劑係選自維生素、礦物質、胺基酸或胺基酸類似物、抗氧化劑、有機酸、聚不飽和脂肪酸、精油、酶、益菌生(prebiotic)、益生菌、藥草、顏料、醫藥活性劑或其組合。
- 如請求項13之營養組合物,其係食品組合物、營養補充劑、膳食補充劑、飼料組合物、飼料預混料、寵物食品、寵物食品補充劑或貓尿路保健食品。
- 一種工業組合物,其包含如請求項1或請求項7之調配物及至少一種選自以下之試劑:溶劑、表面活性劑、潤濕劑、聚合物、塑化劑、黏合劑、填充劑、增稠劑、泡沫控制劑、分散劑、崩解劑、pH調整劑、螯合劑、防腐劑、顏料、熱穩定劑、UV/光穩定劑、阻燃劑、殺生物劑、處理助劑、熱改質劑、抗衝擊改質劑、發泡劑、潤滑劑、成核劑或其組合。
- 一種農業組合物,其包含如請求項1或請求項7之調配物及至少一種選自以下之試劑:除草劑、殺真菌劑、殺蟲劑、肥料、溶劑、表面活性劑、黏合劑、填充劑、潤濕劑、增稠劑、泡沫控制劑、分散劑、崩解劑、pH調整劑、螯合劑、防腐劑、顏料或其組合。
- 一種自包含式(I)化合物之飼料級調配物製備如請求項1或請求項7之調配物之方法,該飼料級調配物進一步包含硫酸根離子、硫酸氫根離子及發色體,該方法包含: (a) 使該包含式(I)化合物之飼料級調配物之水溶液與吸附劑接觸以去除發色體,藉此產生經脫色之水溶液; (b1) 用具有有限水可混溶性之溶劑萃取來自步驟(a)之該經脫色之水溶液,以形成包含該具有有限水可混溶性之溶劑及式(I)化合物之有機相及包含硫酸根及硫酸氫根離子之水相;及 (c1) 自該有機相去除該溶劑以製備如請求項1之調配物; 或 (b2) 使來自步驟(a)之該經脫色之水溶液與至少一種離子交換樹脂接觸,以去除硫酸根及硫酸氫根離子並形成水性析出液;及 (c2) 自該水性析出液去除水以製備如請求項1之調配物。
- 如請求項18之方法,其中該包含式(I)化合物之飼料級調配物之水溶液包含以重量計18%或更少之式(I)化合物。
- 如請求項18之方法,其中使該包含式(I)化合物之飼料級調配物之水溶液在步驟(a)中與該吸附劑接觸之前經過濾。
- 如請求項18之方法,其中該吸附劑係活性木炭。
- 如請求項18之方法,其中步驟(b1)中所使用之該具有有限水可混溶性之溶劑係苯、正丁醇、乙酸丁酯、四氯化碳、氯苯、氯仿、氯甲烷、環己烷、二氯甲烷、1,2-二氯乙烷、二-第三丁基醚、二甲醚、二乙二醇、胺基甲酸二乙基酯、二乙醚、二甘二甲醚、二異丙基醚、乙酸乙酯、乙基第三丁基醚、環氧乙烷、氟苯、庚烷、己烷、甲基異丁基酮、甲基第三丁基醚、戊烷、三氯乙烯、甲苯、二甲苯或其組合。
- 如請求項22之方法,其中該具有有限水可混溶性之溶劑係甲基異丁基酮、乙酸乙酯或甲基第三丁基醚。
- 如請求項18之方法,其中步驟(b2)之該接觸包含與陽離子交換樹脂接觸,之後再與陰離子交換樹脂接觸,或步驟(b2)之該接觸包含與陰離子交換樹脂接觸,之後再與陽離子交換樹脂接觸。
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| TWI791754B (zh) * | 2018-02-09 | 2023-02-11 | 丹麥商托普索公司 | α-羥基化合物的製造方法及其用途 |
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| FR3064006B1 (fr) * | 2017-03-16 | 2019-03-29 | Adisseo France S.A.S. | Procede de fabrication de l'acide-2-hydroxy-4-methylthio-butyrique |
| US11185524B2 (en) | 2019-05-15 | 2021-11-30 | Novus International, Inc. | Means for protecting methionine hydroxy analog from rumen degradation |
| CN110483348B (zh) * | 2019-09-03 | 2021-12-07 | 蓝星安迪苏南京有限公司 | 包含蛋氨酸羟基类似物及其低聚物的混合物及其制备方法 |
| AU2020343325A1 (en) * | 2019-09-06 | 2022-03-03 | Kemin Industries, Inc. | Processes for the preparation of alpha-hydroxy esters by esterification of alpha-hydroxy acids |
| CA3178094A1 (en) * | 2020-05-26 | 2021-12-02 | Olaf SCHLACHTER | Process for preparing pet food and pet food obtainable thereby |
| CN111610273B (zh) * | 2020-06-05 | 2021-02-02 | 常州制药厂有限公司 | 一种硫酸双肼屈嗪有关物质的高效液相色谱分析方法 |
| CN116639710B (zh) * | 2023-04-13 | 2025-08-05 | 河北东丽新材料有限公司 | 一种4,4-二硝基二苯醚副产物的回收处理方法 |
| CN118599065B (zh) * | 2024-06-21 | 2025-01-28 | 山东三佳聚合高分子材料有限公司 | 一种npa净醛水性丙烯酸乳液及其制备方法 |
| US12290084B1 (en) * | 2024-10-31 | 2025-05-06 | Tae Yoon Kim | Composition for improving intestinal beneficial bacteria in companion animals |
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2017
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- 2017-06-21 CA CA3025792A patent/CA3025792A1/en active Pending
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- 2017-06-23 TW TW106120987A patent/TW201803846A/zh unknown
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI791754B (zh) * | 2018-02-09 | 2023-02-11 | 丹麥商托普索公司 | α-羥基化合物的製造方法及其用途 |
| US11882852B2 (en) | 2018-02-09 | 2024-01-30 | Haldor Topsøe A/S | Process of producing alpha-hydroxy compounds and uses thereof |
Also Published As
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| MY198309A (en) | 2023-08-22 |
| AR108876A1 (es) | 2018-10-03 |
| WO2017223172A1 (en) | 2017-12-28 |
| EP3474678A4 (en) | 2020-02-26 |
| CA3025792A1 (en) | 2017-12-28 |
| BR112018075185A2 (pt) | 2019-03-26 |
| CN109310110A (zh) | 2019-02-05 |
| RU2019101813A (ru) | 2020-07-27 |
| US20190016675A1 (en) | 2019-01-17 |
| AU2017280075A1 (en) | 2018-12-13 |
| US20170369434A1 (en) | 2017-12-28 |
| RU2019101813A3 (zh) | 2020-07-27 |
| US10106496B2 (en) | 2018-10-23 |
| RU2738419C2 (ru) | 2020-12-14 |
| EP3474678A1 (en) | 2019-05-01 |
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