烏爾曼二芳醚合成

烏爾曼二芳醚合成，又稱烏爾曼縮合反應、烏爾曼聯苯醚合成、烏爾曼型反應，指酚與芳基鹵化物在銅或銅鹽催化下偶聯為二芳醚。^[1] 例如，對硝基苯酚與溴苯在銅存在下偶聯為對硝基聯苯醚。^[2]

這個反應是烏爾曼反應的變體，也是以德國化學家弗里茨·烏爾曼的名字命名。

反應常在高沸點溶劑（如N-甲基吡咯烷酮、硝基苯、二甲基甲酰胺）中、高溫下（一般超過210°C）和計量的銅存在下進行。反應中需要用到的活性銅粉可通過用鋅還原熱的硫酸銅水溶液來製備。芳鹵底物芳環上的吸電子基或鄰位羧基使反應更容易進行。^[4]

最近發現了在鹼和二胺配體存在下，用催化量的碘化銅介導的烏爾曼二芳醚合成，重新引發了對這個反應的研究興趣。^[5]^[6]

{\rm {\ Cu\!-\!X+Ar\!-\!OH\ +}}

　鹼　

{\rm {\ \rightarrow Cu\!-\!O\!-\!Ar+HX\ +}}

　鹼

{\rm {\ Cu\!-\!O\!-\!Ar+Ar'\!-\!X\rightarrow Ar\!-\!O\!-\!Cu(\!-\!Ar)\!-\!X}}

（氧化加成）

{\rm {\ Ar\!-\!O\!-\!Cu(\!-\!Ar)\!-\!X\rightarrow Ar\!-\!O\!-\!Ar'+Cu\!-\!X}}

（還原消除）

戈爾德貝格反應（Goldberg reaction）是用苯胺或芳基酰胺^[7]^[8]^[9]代替酚進行的烏爾曼二芳醚合成。由德國女化學家、弗里茨·烏爾曼的妻子伊爾瑪·戈爾德貝格^[10]發現。

例如，鄰氯苯甲酸與苯胺縮合，可得芬那酸。^[11]

利用戈爾德貝格反應合成芬那酸

鄰溴苯乙酮與苯甲酰胺進行偶聯的產物，可以用作Camps環化反應的起始原料。^[12]

戈爾德貝格等報道了一種用從碘化亞銅和鄰二氮菲製備的催化劑介導的芳基碘化物和芳胺之間的烏爾曼型芳香胺化偶聯反應。富電子的芳基碘化物也能進行反應，因此這種方法可用於彌補布赫瓦爾德-哈特維希反應有些情況下不適用於富電子芳滷的缺點。^[13]

Hurtley反應（Hurtley reaction）是芳鹵與氫碳酸在鹼和銅或銅鹽存在下進行偶聯。^[14]

這個反應是烏爾曼二芳醚合成的一種變體。原始文獻是用鄰溴苯甲酸與丙二酸酯（和其他二羰基化合物）在乙醇鈉存在下進行偶聯。

化學反應列表

[1]
Fritz Ullmann, Paul Sponagel. Ueber die Phenylirung von Phenolen. Berichte der deutschen chemischen Gesellschaft. 1905, 38 (2): 2211–2212. doi:10.1002/cber.190503802176.
[2]
Ray Q. Brewster and Theodore Groening, "Ether, p-nitrophenyl phenyl （頁面存檔備份，存於互聯網檔案館）", Organic Syntheses, Coll. Vol. 2, p.445.
[3]
Iram Goldberg. Ueber Phenylirungen bei Gegenwart von Kupfer als Katalysator. Berichte der deutschen chemischen Gesellschaft. 1906, 39 (2): 1691–1692. doi:10.1002/cber.19060390298.
[4]
Florian Monnier, Marc Taillefer. Minireview Catalytic CC, CN, and CO Ullmann-Type Coupling Reactions. Angewandte Chemie International Edition. 2009, 48 (38): 6954–6971. doi:10.1002/anie.200804497.
[5]
Buchwald, Stephen L.; et al. Copper-Catalyzed Formation of Carbon-Heteroatom and Carbon-Carbon Bonds. 2003 WO02/085838. 2003.^{[永久失效連結]}
[6]
Irina P. Beletskaya. Copper in cross-coupling reactions: The post-Ullmann chemistry. Coordination Chemistry Reviews. 2004, 248 (21-24): 2337–2364. doi:10.1016/j.ccr.2004.09.014.
[7]
Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. A General and Efficient Copper Catalyst for the Amidation of Aryl Halides and the N-Arylation of Nitrogen Heterocycles. J. Am. Chem. Soc.（Communication）. 2001, 123 (31): 7727–7729. doi:10.1021/ja016226z.
[8]
Klapars, A.; Huang, X.; Buchwald, S. L. A General and Efficient Copper Catalyst for the Amidation of Aryl Halides. J. Am. Chem. Soc.（Article）. 2002, 124 (25): 7421–7428. doi:10.1021/ja0260465.
[9]
Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. The Role of Chelating Diamine Ligands in the Goldberg Reaction: A Kinetic Study on the Copper-Catalyzed Amidation of Aryl Iodides. J. Am. Chem. Soc.（Communication）. 2005, 127 (12): 4120–4121. doi:10.1021/ja050120c.
[10]
Iram Goldberg. Ueber Phenylirungen bei Gegenwart von Kupfer als Katalysator. Berichte der deutschen chemischen Gesellschaft. 1906, 39 (2): 1691–1692. doi:10.1002/cber.19060390298.
[11]
C. F. H. Allen and G. H. W. McKee (1943). "Acridone". Org. Synth.; Coll. Vol. 2: 15.
[12]
Jones, C. P.; Anderson, K. W.; Buchwald, S. L. Sequential Cu-Catalyzed Amidation-Base-Mediated Camps Cyclization: A Two-Step Synthesis of 2-Aryl-4-quinolones from o-Halophenones. J. Org. Chem. 2007, 72 (21): 7968–7973. doi:10.1021/jo701384n.
[13]
H.B. Goodbrand, Nan-Xing Hu. Ligand-Accelerated Catalysis of the Ullmann Condensation: Application to Hole Conducting Triarylamines. Journal of Organic Chemistry. 1999, 64: 670–674. doi:10.1021/jo981804o.
[14]
William Robert Hardy Hurtley. CCXLIV.—Replacement of halogen in orthobromo-benzoic acid. J. Chem. Soc. 1929: 1870–1873. doi:10.1039/JR9290001870.

[1] [1]
Fritz Ullmann, Paul Sponagel. Ueber die Phenylirung von Phenolen. Berichte der deutschen chemischen Gesellschaft. 1905, 38 (2): 2211–2212. doi:10.1002/cber.190503802176.

[2] [2]
Ray Q. Brewster and Theodore Groening, "Ether, p-nitrophenyl phenyl （頁面存檔備份，存於互聯網檔案館）", Organic Syntheses, Coll. Vol. 2, p.445.

[3] [3]
Iram Goldberg. Ueber Phenylirungen bei Gegenwart von Kupfer als Katalysator. Berichte der deutschen chemischen Gesellschaft. 1906, 39 (2): 1691–1692. doi:10.1002/cber.19060390298.

[4] [4]
Florian Monnier, Marc Taillefer. Minireview Catalytic CC, CN, and CO Ullmann-Type Coupling Reactions. Angewandte Chemie International Edition. 2009, 48 (38): 6954–6971. doi:10.1002/anie.200804497.

[5] [5]
Buchwald, Stephen L.; et al. Copper-Catalyzed Formation of Carbon-Heteroatom and Carbon-Carbon Bonds. 2003 WO02/085838. 2003.^{[永久失效連結]}

[6] [6]
Irina P. Beletskaya. Copper in cross-coupling reactions: The post-Ullmann chemistry. Coordination Chemistry Reviews. 2004, 248 (21-24): 2337–2364. doi:10.1016/j.ccr.2004.09.014.

[7] [7]
Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. A General and Efficient Copper Catalyst for the Amidation of Aryl Halides and the N-Arylation of Nitrogen Heterocycles. J. Am. Chem. Soc.（Communication）. 2001, 123 (31): 7727–7729. doi:10.1021/ja016226z.

[8] [8]
Klapars, A.; Huang, X.; Buchwald, S. L. A General and Efficient Copper Catalyst for the Amidation of Aryl Halides. J. Am. Chem. Soc.（Article）. 2002, 124 (25): 7421–7428. doi:10.1021/ja0260465.

[9] [9]
Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. The Role of Chelating Diamine Ligands in the Goldberg Reaction: A Kinetic Study on the Copper-Catalyzed Amidation of Aryl Iodides. J. Am. Chem. Soc.（Communication）. 2005, 127 (12): 4120–4121. doi:10.1021/ja050120c.

[10] [10]
Iram Goldberg. Ueber Phenylirungen bei Gegenwart von Kupfer als Katalysator. Berichte der deutschen chemischen Gesellschaft. 1906, 39 (2): 1691–1692. doi:10.1002/cber.19060390298.

[11] [11]
C. F. H. Allen and G. H. W. McKee (1943). "Acridone". Org. Synth.; Coll. Vol. 2: 15.

[12] [12]
Jones, C. P.; Anderson, K. W.; Buchwald, S. L. Sequential Cu-Catalyzed Amidation-Base-Mediated Camps Cyclization: A Two-Step Synthesis of 2-Aryl-4-quinolones from o-Halophenones. J. Org. Chem. 2007, 72 (21): 7968–7973. doi:10.1021/jo701384n.

[13] [13]
H.B. Goodbrand, Nan-Xing Hu. Ligand-Accelerated Catalysis of the Ullmann Condensation: Application to Hole Conducting Triarylamines. Journal of Organic Chemistry. 1999, 64: 670–674. doi:10.1021/jo981804o.

[14] [14]
William Robert Hardy Hurtley. CCXLIV.—Replacement of halogen in orthobromo-benzoic acid. J. Chem. Soc. 1929: 1870–1873. doi:10.1039/JR9290001870.

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烏爾曼二芳醚合成

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烏爾曼二芳醚合成

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反應機理

戈爾德貝格反應

Hurtley反應

參見

參考資料