藥物合成反應(yīng)第三章?；磻?yīng)(參考版)
2025-05-29 18:21本頁面
【正文】 RO39。 R C HC COR 39。 39。+二、烯烴的 C?；? R CH C H 2R CHCH39。 ? (3) the regioselectivity is not high, but orthoformyl products tend to predominate。 A r O H + N a O H + C H C l 3C C l4A r C H O△CC lC lC lCC lC lC lHC H C l 3O H C l C C l 2卡 賓機(jī) 理 :? (1) it is the only electrophilic aromatic substitution reaction that occurs under basic conditions in a protic solvent。 ? (3) mostly electronrich aromatic or heteroaromatic pounds as well as electronrich alkenes and 1,3dienes11 are substrates。 ? (8) A serious limitation of both title reactions is that they cannot be used for the formylation of aromatic amines due to numerous side reactions. RNRC HO RN HR+ P O C l 3 + A r HH 2 OA r C H O +通 式在 芳 環(huán) 上 導(dǎo) 入 甲 醛N H 2N H 2O HO HRRH OS…A r ：4 Vilsmelier反應(yīng) 用 N取代甲酰胺作?；瘎?，三氯氧磷催化芳環(huán)甲?；姆磻?yīng) RNRCHO PC lC l C lORNRC H+RNRC HC lO RHCC lNRRO RC H OO R親 電 取 代H2Oα 氯 化 亞 胺C lO P O C l2 反應(yīng)機(jī)理 VilsmeierHaack formylation ? 例 S SC H O① D M F / P O C l 3② H 2 OC H O① D M F / P O C l 3② H 2 OV i l s m e i e r? (1) the Vilsmeier reagent is prepared from any N,Ndisubstituted formamide by reacting it with an acid chloride (., POCl3, SOCl2, oxalyl chloride)。 ? (6) R. Adams generated it in situ along with ZnCl2 by reacting Zn(CN)2 with HCl in the presence of the aromatic substrate (Adams modification)。 however, no activator is needed at high pressure ? (3) monosubstituted substrates are formylated almost exclusively at the para position, but when there is already a para substituent present in the substrate, the formyl group is introduced at the ortho position。 O HH OO HO HH OO HCH 3 C N HO HH OO HCH 3 C O+ C H 3 C NH C l / Z n C l 2 H2 OC H 3H 3 CC H 3C H 3H 3 CC H 3C H OZ n ( C N ) 2 / H C lH 2 OZ n ( C N ) 2 + 2 H C l 2 H C N + Z n C l 2? GattermannKoch formylation ? (1) at high CO pressure (100250 atm) the reaction rate increases significantly and even nonactivated aromatics (chlorobenzene, benzene) can be formylated。 ? unlike in the alkylations, FriedelCrafts acylations require substantial amounts of catalyst (slightly more than one equivalent), since the acylating agent itself coordinates one equivalent of Lewis acid, and therefore excess is needed to observe catalysis。 ? unprotected Lewis basic functional groups (., amines) are poor substrates, since the acylation will preferentially take place on these functional groups instead of the aromatic ring。 +H C l( 加 去 酸 劑 ： 有 機(jī) 堿 P y , E t 3 N )HC C O C lN H H C lSNM e 3 S i O O CC H 3H 2 NO+E t 3 NC H 3 C N , 2 5 ℃4 酰氯為?；瘎? C H CON H 2SNH O O CC H 3HNO 脂 肪 胺 ＞ 芳 胺 N H 2Rp π 共 軛因 為二、芳胺 N?；? C O O E tC O O E tN H 2C lC O N HC O N HC lC l+ 2N a ? 第四節(jié) 碳原子上的?；磻?yīng) 一、芳烴的 C酰化 1 FriedelCrafts (FC )傅 克?；磻?yīng) R COZC RO+L e w i s ( Z = X , O C O R , O H , O R 39。3 酸酐為酰化劑 C OC OOC OC O O HH NC H C H 2 P hC O O H △C OC ON C H C H 2 P hC O O HP h C H 2 C H C O O HN H 2如用環(huán)狀酸酐?；瘯r，在低溫下常生成單?；a(chǎn)物，高溫加熱則可得雙酰化亞胺 ? R C C lOR CHN RO39。+ H 2 N R 39。RCC O O E tC O O E t+N HCCC N HCRROOO39。 + H O R 39。+ H 2 N R 39。OR C N H RO 39。 R C O N H R 39。 N R 39。39。 S O 2 O HC lC lC lC O C lC lC lC lC ROOOC+ R C O O H? iv 羧酸 磷酸混合酸酐 ? BOPCl DPPA ?其它 混合酸酐 ? CC lOC lCC lOO E tCE t O
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