一种氧气氧化醇或醛制备酸的方法转让专利
申请号 : CN202110259272.3
文献号 : CN113004108B
文献日 : 2022-06-07
发明人 : 麻生明 , 姜兴国
申请人 : 中国科学院上海有机化学研究所
摘要 :
权利要求 :
1.一种氧气氧化醛的方法,其特征在于,在室温下,在有机溶剂中,以氧气作为氧化剂,以醛为原料,以硝酸铁、2,2,6,6‑四甲基哌啶氮氧化物、无机卤化物作为催化剂,在中性条件下反应,所述醛氧化生成酸;
其中,
所述原料醛是R2CHO;R2包括C1‑C16的碳链,C3‑C8的碳环或杂环,含有氟、氯、溴、碘、芳基、杂环、酯基、醚键、炔基、双键官能团的烷基、萜类、甾体结构;
所述原料、硝酸铁、2,2,6,6‑四甲基哌啶氮氧化物、无机卤化物的摩尔比为100:10:10~20:10;所述无机卤化物是氯化钾;
所述反应的时间为12‑48小时。
2.如权利要求1所述氧气氧化醛的方法,其特征在于,
所述芳基为苯基、烷氧基苯基、硝基苯基、卤代苯基、噻吩基、呋喃基或萘基;所述烷氧基苯基为甲氧基苯基、乙氧基苯基,所述卤代苯基为氟代苯基、氯代苯基、溴代苯基、碘代苯基;
所述杂环为呋喃环、噻吩环。
3.如权利要求1所述氧气氧化醛的方法,其特征在于,所述原料、硝酸铁、2,2,6,6‑四甲基哌啶氮氧化物、无机卤化物的摩尔比为100:10:10:10。
4.如权利要求1所述氧气氧化醛的方法,其特征在于,所述氧气为纯的氧气或空气中的氧气。
5.如权利要求1所述氧气氧化醛的方法,其特征在于,所述中性条件是指不添加质子酸或碱。
6.如权利要求1所述氧气氧化醛的方法,其特征在于,所述有机溶剂为乙酸乙酯、二氯甲烷、1,2‑二氯乙烷、1,1‑二氯乙烷、1,2‑二氯丙烷、1,3‑二氯丙烷、硝基甲烷、乙二醇二甲醚、二氧六环、四氢呋喃、乙腈、苯或甲苯中的一种或多种混合。
7.如权利要求1所述氧气氧化醛的方法,其特征在于,所述氧气可以是空气中的氧气;
其中,通空气时采用的方法为以空气袋作为氧气的主要来源,反应1.5小时后,增加氧气球作为补充;或通过缓慢空气流方法,使空气缓慢流过反应容器。
说明书 :
一种氧气氧化醇或醛制备酸的方法
技术领域
背景技术
Thottathil,J.K.;Moniot,J.L.;Mueller,R.H.;Wong,M.K.Y.;Kissick,
T.P.J.Org.Chem.1986,51,3140‑3143)。氧气是一种廉价易得、清洁、高原子经济性、环境友好的氧化剂。空气是更为理想的氧化剂,无需制备和运输,在工业生产中更为安全。目前,以氧气为氧化剂实现从醇到酸的氧化方法非常有限,且集中在贵金属催化领域,空气氧化的报道更为少见。如1940‑年代发展的Pt催化的Heyns氧化,然而Pt昂贵的价格和易于毒化的特点限制了Heyns氧化在工业生产上的应用;姜标小组在2014年以Ag(NHC)/KOH体系实现了利用干燥的空气氧化卞醇生成酸;Davis等人报道了Au/H2O界面催化乙醇和丙三醇生成酸;
张泽会等人报道了负载的磁性Pd纳米催化剂催化氧气氧化5‑羟甲基糠醛生成2,5‑呋喃二甲酸;Buffin等人报道了Pd催化下,醇可被氧气氧化为羧酸和酯的混合物,卞醇可被氧化为醛和酸的混合物;2015年,李朝军小组报道了在AgO2/IPr体系中,由氧气氧化醛生成酸。Ag、Au、Ru、Pd等金属催化的氧化反应也有一定报道,但底物局限性强,大多需要纳米技术或负载实现(Dalmer,O.;Heyns,K.U.S.Pat.1940,2,190,377;Han,L.;Xing,P.;Jiang,B.Org.Lett.2014,16,3428‑3431;Zope,B.N.;Hibbitts,D.D.;Neurock,M.;Davis,R.J.Science,2010,330,74‑78;Kerdi,F.;Rass,H.A.;Pinel,C.;Besson,M.;Peru,G.;
Leger,B.;Rio,S.;Monflier,E.;Ponchel,A.Appl.Catal.A.2015,506,206‑219;Buffin,B.P.;Clarkson,J.P.;Belitz,N.L.;Kundu,A.J.Mol.Catal.A.2005,225,111‑116;eLiu,M.X.;Wang,H.N.;Zeng,H.Y.;Li,C.J.Sci.Adv.2015,1,e1500020)。TEMPO能提供一种稳定的氧自由基,在与Fe或者Cu协同催化氧化醇得到醛或酮的过程中发挥了重要的作用(Stahl S.S.;Ryland,B.L.Angew.Chem.Int.Ed.2014,53,8824‑8838;Cao,Q.;Dornan,L.M.;Rogan,L.;Hughes,N.L.;Muldoon,M.J.Chem.Commun.,2014,50,4524‑4543)。但在此类体系中还未能实现氧气氧化醇或醛生成酸的报道。
发明内容
通过β‑消除和还原消除得到了醛,TEMPOH,Fe 。在反应体系中,Fe 可以在NO2作用下重新被
3+ 2 2 3+
氧化为Fe ,而NO被还原为NO。NO 通过NO与O2的反应再生。TEMPOH通过和Fe 的反应被转化
3+
回到TEMPO。醛的水合物Int 3通过H2O在Fe 的调节下进攻醛生成。醛的水合物Int 3经历一个相似的过程得到羧酸,如图1所示。
附图说明
具体实施方式
胶柱层析(石油醚:乙酸乙酯=5:1)得到相应的十二酸(199.2mg,100%)。H NMR(400MHz,CDCl3)δ11.68(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),1.63(quint,J=7.3Hz,2H,CH2),
13
1.39‑1.21(m,16H,8×CH2),0.88(t,J=7.0Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.7,
34.1,31.9,29.6,29.4,29.3,29.2,29.0,24.6,22.7,14.1.
85%)。H NMR(400MHz,CDCl3)δ11.47(brs,1H,COOH),2.35(t,J=7.4Hz,2H,CH2),1.63
13
(quint,J=7.4Hz,2H,CH2),1.39‑1.21(m,8H,4×CH2),0.88(t,J=7.0Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.6,34.1,31.6,29.0,28.9,24.6,22.6,14.0.
间为12小时,得到苯丙酸(147.1mg,98%)。H NMR(400MHz,CDCl3)δ11.48(brs,1H,COOH),
13
7.33‑7.15(m,5H,Ar‑H),2.95(t,J=8.0Hz,2H,CH2),2.67(t,J=7.8Hz,2H,CH2);C NMR(100MHz,CDCl3)δ179.6,140.1,128.5,128.2,126.3,35.6,30.5.
100/1重结晶)(文献值:62.2–63.3℃);H NMR(400MHz,CDCl3)δ11.60(brs,1H,COOH),2.35(t,J=7.4Hz,2H,CH2),1.63(quint,J=7.4Hz,2H,CH2),1.38‑1.19(m,24H,12×CH2),0.88
13
(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.7,34.1,31.9,29.71,29.69,29.68,‑1
29.66,29.65,29.60,29.44,29.37,29.2,29.1,24.7,22.7,14.1;IR(neat,cm ):3300‑+
2300,1698,1471,1430,1310,1293,1271,1250,1228,1207,1188;MS(EI)m/z(%):256(M ,
60.14),73(100).
H NMR(400MHz,CDCl3)δ9.21(brs,1H,COOH),3.68(s,3H,CH3),2.43‑2.31(m,4H,2×CH2),
13
1.75‑1.62(m,4H,2×CH2);C NMR(100MHz,CDCl3)δ179.4,173.8,51.6,33.6,24.2,24.0;
‑1
IR(neat,cm ):3400‑2700,1736,1707,1438,1416,1367,1259,1199,1175,1143,1080,‑
1016.MS(ESI,Neg)m/z(%):159(M‑1) .
间为12小时,得到8‑乙酰氧基辛酸(188.3mg,93%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ9.58(brs,1H,COOH),4.05(t,J=6.6Hz,2H,CH2),2.35(t,J=7.4Hz,2H,
13
CH2),2.05(s,3H,CH3),1.69‑1.57(m,4H,2×CH2),1.42‑1.30(m,6H,3×CH2);C NMR
(100MHz,CDCl3)δ179.9,171.4,64.5,33.9,28.81,28.78,28.4,25.6,24.5,20.9;IR(neat,‑1 +
cm ):3600‑2400,1706,1464,1413,1391,1366,1234,1100,1036;MS(EI)m/z(%):202(M ,
2.51),55(100).
1
5:1到2:1)。H NMR(400MHz,CDCl3)δ9.82(brs,1H,COOH),4.52(dd,J1=8.6Hz,J2=5.4Hz,
1H,CH),4.09‑4.00(m,1H,one proton of CH2),3.99‑3.90(m,1H,one proton of CH2),
2.38‑2.27(m,1H,one proton of CH2),2.16‑2.06(m,1H,one proton of CH2);2.04‑1.89
13 ‑1
(m,2H,CH2);C NMR(100MHz,CDCl3)δ177.8,76.2,69.6,30.1,25.2;IR(neat,cm ):3400‑+
2600,1722,1449,1411,1351,1310,1203,1176,1072,1037;MS(EI)m/z(%):116(M ,1.09),
71(100).
62.4℃(石油醚/乙酸乙酯重结晶)(文献值:61‑62.5℃);H NMR(400MHz,CDCl3)δ10.89
13
(brs,1H,COOH),7.24‑7.20(m,1H,Ar‑H),6.98‑6.94(m,2H,Ar‑H),3.87(s,2H,CH2);C NMR‑1
(100MHz,CDCl3)δ177.0,134.0,127.2126.9,125.3,35.0;IR(neat,cm ):3300‑2300,1692,+
1438,1417,1399,1362,1331,1222,1188,1148,1128,1081,1040;MS(EI)m/z(%):142(M ,
48.52),97(100).
点:35.3‑36.5℃(石油醚/乙酸乙酯重结晶)(文献值:35‑36.5℃);H NMR(400MHz,CDCl3)δ
11.54(brs,1H,COOH),3.41(t,J=6.8Hz,2H,CH2),2.36(t,J=7.6Hz,2H,CH2),1.85(quint,
13
J=7.2Hz,2H,CH2),1.63(quint,J=7.3Hz,2H,CH2),1.48‑1.28(m,8H,4×CH2);C NMR‑1
(100MHz,CDCl3)δ180.4,34.0,33.9,32.7,29.0,28.8,28.5,28.0,24.5;IR(neat,cm ):
3100‑2500,1689,1468,1427,1406,1338,1303,1275,1241,1211,1188,1097,1043;MS(EI)
81 + 79 +
m/z(%):238(M( Br) ,1.16),236(M( Br) ,1.16),60(100).
反应时间为12小时,得到2‑己氧基乙酸(147.7mg,92%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ10.14(brs,1H,COOH),4.13(s,2H,CH2),3.56(t,J=6.8Hz,2H,CH2),
13
1.67‑1.59(m,2H,CH2),1.41‑1.24(m,6H,3×CH2),0.88(t,J=7.0Hz,3H,CH3);C NMR‑1
(100MHz,CDCl3)δ175.6,72.1,67.6,31.5,29.3,25.5,22.5,13.9.IR(neat,cm ):3600‑+
2500,2930,2862,1729,1462,1431,1239,1126,298,807,727,676;MS(EI)m/z(%):160(M ,
2.82),83(100).
12小时,得到7‑辛炔酸(111.7mg,80%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ11.41(brs,1H,COOH),2.38(t,J=7.4Hz,2H,CH2),2.20(td,J1=6.9Hz,J2=2.5Hz,
2H,≡CCH2),1.95(t,J=2.6Hz,2H,≡CH),1.71‑1.61(m,2H,CH2),1.60‑1.42(m,4H,2×
13
CH2);C NMR(100MHz,CDCl3)δ180.3,84.2,68.4,33.9,28.02,27.98,24.1,18.2.
应时间为12小时,得到4‑戊炔酸(59.3mg,60%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ11.29(brs,1H,COOH),2.66‑2.60(m,2H,CH2),2.56‑2.48(m,2H,CH2),2.01
13
(t,J=2.8Hz,1H,≡CH);C NMR(100MHz,CDCl3)δ178.2,82.1,69.2,33.1,14.0.
间为12小时,得到10‑十一炔酸(186.5mg,95%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ11.18(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),2.15‑2.08(m,2H,CH2),
1.78(t,J=2.6Hz,3H,CH3),1.63(quint,J=7.3Hz,2H,CH2),1.46(quint,J=7.2Hz,2H,
13
CH2),1.41‑1.24(m,8H,4×CH2);C NMR(100MHz,CDCl3)δ180.5,79.3,75.3,34.1,29.1,
28.98,28.95,28.91,28.8,24.6,18.7,3.4.
应时间为36小时,得到3‑三甲基硅基丙炔酸(93.7mg,66%)(石油醚:乙酸乙酯=5:1)。H
13
NMR(400MHz,CDCl3)δ9.91(brs,1H,COOH),0.26(s,9H,3×CH3);C NMR(100MHz,CDCl3)δ‑1
157.6,97.4,93.8,‑1.0;IR(neat,cm ):3600‑2500,2964,2176,1687,1400,1252,913,840,+
760;MS(EI)m/z(%):142(M ,12.82),75(100).
1
=5:1)。H NMR(400MHz,CDCl3)δ11.01(brs,1H,COOH),5.74‑5.64(m,2H,CH=CH),2.65‑
13
2.56(m,1H,CH),2.35‑2.25(m,2H,CH2),2.20‑1.99(m,3H,CH2),1.78‑1.65(m,1H,CH2);C +
NMR(100MHz,CDCl3)δ182.5,126.6,124.8,39.0,27.0,24.7,24.2.MS(EI)m/z(%):126(M ,
27.78),79(100).
(文献值:144℃);H NMR(400MHz,DMSO‑d6)δ12.00(s,3H,CH3),2.19(t,J=7.2Hz,4H,2×
13 6
CH2),1.54‑1.42(m,4H,2×CH2),1.31‑1.20(m,4H,2×CH2);C NMR(100MHz,d ‑DMSO)δ‑1
174.5,33.6,28.3,24.4.IR(neat,cm ):3500‑2200,1688,1466,1408,1332,1252,1190,+
1065,1011.MS(EI)m/z(%):174(M ,0.23),138(100).
28.7
123.7‑124.5℃(石油醚/乙酸乙酯重结晶)(文献值:121‑124℃);比旋光[α]D =47.9(c=
20 1
1.01,CHCl3)(文献值:[α]D =47(c=1.01,CHCl3));H NMR(400MHz,CDCl3)δ2.41(dd,J1=
16.0Hz,J2=14.8Hz,1H,one proton of CH2),2.23(dd,J1=16.4Hz,J2=6.4Hz,1H,CH2),
2.08(dt,J1=11.6Hz,J2=3.2Hz,1H),1.97(dd,J1=14.8Hz,J2=6.6Hz,1H,CH2),1.92‑1.84(m,1H,CH2),1.74‑1.60(m,2H,CH2),1.50‑1.31(m,7H),1.20(dt,J1=14.0Hz,J2=4.0Hz,
13
1H,CH2),1.10‑1.00(m,2H),0.91(s,3H,CH3),0.89(s,3H,CH3),0.84(s,3H,CH3);C NMR(100MHz,CDCl3)δ176.8,86.3,59.0,56.5,42.0,39.3,38.6,35.9,33.05,32.99,28.6,‑1
21.4,20.8,20.4,18.0,14.9;IR(neat,cm ):2928,2897,2869,1766,1460,1390,1223,+
1178,1122,1017;MS(EI)m/z(%):250(M ,3.96),123(100).
139.9‑142.1℃(石油醚/乙酸乙酯重结晶)(文献值:137.7℃);比旋光[α]D =28.7(c=
25.3 1
1.02,CHCl3)(文献值:[α]D =28.1(c=0.01,CHCl3));H NMR(400MHz,CDCl3)δ11.45(brs,1H,COOH),2.70(t,J=14.2Hz,1H,CH2),2.46‑2.22(m,3H),2.21‑2.13(m,1H),2.08‑
1.98(m,3H),1.94‑1.76(m,4H),1.65‑1.55(m,1H),1.55‑1.04(m,15H),1.02(s,3H,CH3),
13
0.93(d,J=6.4Hz,3H,CH3),0.69(s,3H,CH3);C NMR(100MHz,CDCl3)δ213.9,180.4,56.3,
55.8,44.2,42.7,42.2,40.5,39.9,37.1,36.9,35.4,35.2,34.8,31.0,30.6,28.1,26.5,‑1
25.7,24.1,22.6,21.1,18.2,12.0.IR(neat,cm ):3400‑2500,1699,1448,1412,1380,+
1304,1262,1225,1182,1099.MS(EI)m/z(%):374(M ,12.22),55(100).
73.4℃(石油醚/乙酸乙酯重结晶)(文献值:72‑74℃).H NMR(400MHz,CDCl3)δ7.94(d,J=
7.6Hz,1H,Ar‑H),7.70(td,J1=7.6Hz,J2=0.8Hz,1H,Ar‑H),7.57‑7.48(m,2H,Ar‑H),5.34
13
(s,2H,CH2);C NMR(100MHz,CDCl3)δ171.0,146.5,133.9,128.9,125.6,125.6,122.1,‑1
69.6;IR(neat,cm ):2944,2924,1745,1615,1593,1466,1436,1364,1317,1286,1191,+
1108,1047;MS(EI)m/z(%):134(M ,46.06),105(100).
空旋干溶剂后,硅胶柱层析(石油醚:乙酸乙酯=5:1)纯化得到十二酸(189.7mg,95%)。H NMR(400MHz,CDCl3)δ11.68(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),1.63(quint,J=
13
7.3Hz,2H,CH2),1.39‑1.21(m,16H,8×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,‑1
CDCl3)δ180.7,34.1,31.9,29.6,29.4,29.3,29.2,29.0,24.6,22.7,14.1.IR(neat,cm ):
+
3400‑2500,1694,1466,1429,1351,1301,1278,1247,1218,1192;MS(EI)m/z(%):200(M ,
21.87),73(100).
间为16小时,得到辛酸(128.6mg,89%)(石油醚:乙酸乙酯=5:1)。H NMR(400MHz,CDCl3)δ
10.26(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),1.63(quint,J=7.4Hz,2H,CH2),1.39‑
13
1.22(m,8H,4×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.5,34.1,‑1
31.6,29.0,28.9,24.6,22.6,14.0;IR(neat,cm ):2925,2857,1707,1462,1413,1277,+
1231,1203,1109,933,725;MS(EI)m/z(%):144(M ,3.74),60(100).
47.6℃(石油醚/乙酸乙酯重结晶);H NMR(400MHz,CDCl3)δ10.35(brs,1H,COOH),7.33‑
13
7.16(m,5H,Ar‑H),2.95(t,J=7.8Hz,2H,CH2),2.68(t,J=7.8Hz,2H,CH2);C NMR
‑1
(100MHz,CDCl3)δ179.4,140.1,128.5,128.2,126.3,35.6,30.5;IR(neat,cm ):3400‑+
2400,1693,1448,1427,1300,1216,928,785,753,723,698;MS(EI)m/z(%):150(M ,38),91(100).
反应时间为16小时,得到十六烷基酸(250.5mg,98%)。H NMR(400MHz,CDCl3)δ11.43(brs,
1H,COOH),2.35(t,J=7.4Hz,2H,CH2),1.63(quint,J=7.4Hz,2H,CH2),1.36‑1.21(m,24H,
13
12×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.6,34.1,31.9,29.70,
29.68,29.66,29.65,29.60,29.44,29.37,29.2,29.1,24.7,22.7,14.1.
H NMR(400MHz,CDCl3)δ9.10(brs,1H,COOH),3.68(s,3H,CH3),2.43‑2.30(m,4H,2×CH2),
13
1.75‑1.62(m,4H,2×CH2);C NMR(100MHz,CDCl3)δ179.3,173.8,51.6,33.6,24.2,24.0.[0127] 实施例25:8‑乙酰氧基辛酸的合成
间为16小时,得到8‑乙酰氧基辛酸(188.9mg,93%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ10.62(brs,1H,COOH),4.05(t,J=6.6Hz,2H,CH2),2.35(t,J=7.6Hz,2H,
13
CH2),2.05(s,3H,CH3),1.69‑1.57(m,4H,2×CH2),1.42‑1.30(m,6H,3×CH2);C NMR
(100MHz,CDCl3)δ180.0,171.4,64.5,33.9,28.82,28.78,28.4,25.6,24.5,20.9.
1
5:1到2:1)。H NMR(400MHz,CDCl3)δ9.74(brs,1H,COOH),4.51(dd,J1=8.6Hz,J2=5.4Hz,
1H,CH),4.09‑4.01(m,1H,one proton of CH2),3.99‑3.91(m,1H,one proton of CH2),
2.38‑2.27(m,1H,one proton of CH2),2.17‑2.06(m,1H,one proton of CH2);2.04‑1.89
13
(m,2H,CH2);C NMR(100MHz,CDCl3)δ177.8,76.3,69.6,30.1,25.2.
(132.0mg,1.0mmol)。H NMR(400MHz,CDCl3)δ10.90(brs,1H,COOH),7.25‑7.21(m,1H,Ar‑
13
H),6.98‑6.93(m,2H,Ar‑H),3.87(s,2H,CH2);C NMR(100MHz,CDCl3)δ177.0,133.9,
127.2126.9,125.3,35.0.
反应时间为16小时,得到9‑溴‑1‑壬酸(233.5mg,98%)(石油醚:乙酸乙酯=5:1到3:1)。H NMR(400MHz,CDCl3)δ11.59(brs,1H,COOH),3.41(t,J=6.8Hz,2H,CH2),2.35(t,J=7.4Hz,
2H,CH2),1.85(quint,J=7.2Hz,2H,CH2),1.63(quint,J=7.3Hz,2H,CH2),1.48‑1.27(m,
13
8H,4×CH2);C NMR(100MHz,CDCl3)δ180.5,34.0,33.9,32.7,29.0,28.9,28.5,28.0,
24.5.
1
到2:1)。H NMR(400MHz,CDCl3)δ8.83(brs,1H,COOH),4.12(s,2H,CH2),3.56(t,J=6.6Hz,
13
2H,CH2),1.68‑1.58(m,2H,CH2),1.41‑1.24(m,6H,3×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ175.7,72.1,67.6,31.5,29.3,25.5,22.5,13.9.
为16小时,得到7‑辛炔酸(112.2mg,80%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ11.01(brs,1H,COOH),2.38(t,J=7.6Hz,2H,CH2),2.21(td,J1=6.9Hz,J2=2.5Hz,
2H,≡CCH2),1.95(t,J=2.6Hz,1H,≡CH),1.71‑1.62(m,2H,CH2),1.61‑1.42(m,4H,2×
13
CH2);C NMR(100MHz,CDCl3)δ180.1,84.2,68.4,33.9,28.04,27.99,24.1,18.2.IR(neat)‑1
ν(cm )3298,2940,2864,2117,1707,1461,1413,1278,1225,1141,1085;MS(ESI,Neg)m/z‑
(%):139(M‑1) .
55.9‑57.0℃(石油醚/乙酸乙酯重结晶);H NMR(400MHz,CDCl3)δ11.37(brs,1H,COOH),
13
2.66‑2.60(m,2H,CH2),2.56‑2.49(m,2H,CH2),2.01(t,J=2.6Hz,1H,≡CH);C NMR‑1
(100MHz,CDCl3)δ178.3,82.0,69.2,33.1,14.0.IR(neat)ν(cm )3500‑2000,3276,2927,+
2627,2119,1694,1426,1353,1299,1217,1024,890.MS(EI)m/z(%):98(M ,3.7),70(100)[0148] 实施例32:10‑十一炔酸的合成
51.3‑52.2℃(石油醚/乙酸乙酯重结晶);H NMR(400MHz,CDCl3)δ9.57(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),2.15‑2.08(m,2H,CH2),1.78(t,J=2.6Hz,3H,CH3),1.63(quint,J=
13
7.3Hz,2H,CH2),1.46(quint,J=7.1Hz,2H,CH2),1.41‑1.24(m,8H,4×CH2);C NMR
(100MHz,CDCl3)δ180.4,79.3,75.3,34.1,29.1,28.98,28.96,28.91,28.8,24.6,18.7,‑1
3.4.IR(neat)ν(cm )3500‑2400,1693,1464,1434,1410,1347,1321,1293,1260,1226,+
1193.MS(EI)m/z(%):196(M ,0.57),68(100).
应时间为48小时,得到3‑三甲基硅基丙炔酸(92.9mg,65%)(石油醚:乙酸乙酯=5:1)。H
13
NMR(400MHz,CDCl3)δ6.78(brs,1H,COOH),0.26(s,9H,3×CH3);C NMR(100MHz,CDCl3)δ
157.4,97.4,93.7,‑1.0.
1
5:1)。H NMR(400MHz,CDCl3)δ11.63(brs,1H,COOH),5.75‑5.60(m,2H,CH2),2.68‑2.55(m,
13
1H,CH),2.36‑2.00(m,5H,CH2),1.78‑1.65(m,1H,CH2);C NMR(100MHz,CDCl3)δ182.7,
126.7,124.9,39.1,27.1,24.8,24.3.
时间为48小时,得到辛二酸(144.4mg,83%)(乙酸乙酯/正己烷重结晶)。H NMR(400MHz,DMSO‑d6)δ12.00(s,3H,CH3),2.19(t,J=7.4Hz,4H,2×CH2),1.54‑1.41(m,4H,2×CH2),
13 6
1.31‑1.21(m,4H,2×CH2);C NMR(100MHz,d‑DMSO)δ174.5,33.6,28.3,24.4.
28.7 20 1
[α]D =46.9(c=1.00,CHCl3)(文献值:[α]D =47(c=1.01,CHCl3));H NMR(400MHz,CDCl3)δ2.41(dd,J1=15.6Hz,J2=15.6Hz,1H,CH2),2.23(dd,J1=15.0Hz,J2=6.4Hz,1H,CH2),2.08(dt,J1=11.6Hz,J2=3.3Hz,1H),1.97(dd,J1=14.8Hz,J2=6.6Hz,1H,CH2),
1.92‑1.84(m,1H,CH2),1.74‑1.63(m,2H,CH2),1.50‑1.31(m,7H),1.20(dt,J1=13.5Hz,J2=4.3Hz,1H,CH2),1.10‑1.00(m,2H),0.91(s,3H,CH3),0.89(s,3H,CH3),0.84(s,3H,CH3);
13
C NMR(100MHz,CDCl3)δ176.7,86.2,59.0,56.5,42.0,39.4,38.6,35.9,33.05,32.99,
28.6,21.5,20.8,20.4,18.0,14.9.
应时间为16小时,得到苯酞(88.3mg,66%)(石油醚:乙酸乙酯=15:1到10:1)。H NMR(400MHz,CDCl3)δ7.92(d,J=7.6Hz,1H,Ar‑H),7.70(td,J1=7.6Hz,J2=1.2Hz,1H,Ar‑H),
13
7.58‑7.49(m,2H,Ar‑H),5.34(s,2H,CH2);C NMR(100MHz,CDCl3)δ171.1,146.5,134.0,
129.0,125.62,125.57,122.1,69.6.
5.0mmol)和1,2‑二氯乙烷(DCE,20.0mL)。反应在室温下搅拌20小时,TLC监测(石油醚:乙酸乙酯=5:1)直至反应完成。反应混合物经过粗硅胶短柱过滤,乙醚(3×40mL)淋洗。真空旋
1
干溶剂,硅胶柱层析(石油醚:乙酸乙酯=5:1到2:1)得到产品7‑辛炔酸(599.1mg,85%)。H NMR(400MHz,CDCl3)δ11.29(brs,1H,COOH),2.38(t,J=7.6Hz,2H,CH2),2.20(td,J1=
7.0Hz,J2=2.8Hz,2H,C≡CCH2),1.95(t,J=2.8Hz,1H,C≡CH),1.71‑1.61(m,2H,CH2),
13
1.60‑1.41(m,4H,2×CH2);C NMR(100MHz,CDCl3)δ180.3,84.2,68.4,33.9,28.02,27.99,
24.1,18.2.
1
94%)。H NMR(400MHz,DMSO‑d6)δ11.99(brs,1H,COOH),2.18(t,J=7.4Hz,2H,CH2),1.53‑
13
1.42(m,2H,CH2),1.32‑1.16(m,24H,12×CH2),0.85(t,J=6.6Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.8,34.1,31.9,29.69,29.67,29.66,29.59,29.43,29.37,29.2,29.0,24.6,
22.7,14.1.
120mL)淋洗.真空旋干溶剂后,粗产品重结晶(石油醚:乙酸乙酯=15:1)纯化得到十六烷基
1
酸(9.0540g,88%)。H NMR(400MHz,DMSO‑d6)δ11.99(brs,1H,COOH),2.18(t,J=7.4Hz,2H,
13
CH2),1.52‑1.43(m,2H,CH2),1.30‑1.19(m,24H,12×CH2),0.85(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.6,34.1,31.9,29.70,29.69,29.67,29.66,29.65,29.59,29.44,
29.37,29.24,29.1,24.7,22.7,14.1.
1
油醚:乙酸乙酯=20:1)纯化得到十六烷基酸(55.0232g,89%)。H NMR(400MHz,DMSO‑d6)δ
11.99(brs,1H,COOH),2.18(t,J=7.4Hz,2H,CH2),1.52‑1.43(m,2H,CH2),1.31‑1.18(m,
13
24H,12×CH2),0.85(t,J=6.6Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.5,34.1,31.9,
29.67,29.65,29.64,29.62,29.57,29.42,29.35,29.2,29.0,24.7,22.7,14.1.
酯重结晶)(文献值:43‑44℃);H NMR(400MHz,CDCl3)δ=11.56(brs,1H,COOH),2.35(t,J=
7.4Hz,2H,CH2),1.63(quint,J=7.1Hz,2H,CH2),1.40‑1.18(m,16H,8×CH2),0.88(t,J=
13
6.6Hz,3H,CH3);C NMR(100MHz,CDCl3)δ180.6,34.1,31.9,29.6,29.4,29.3,29.2,29.0,+
24.7,22.7,14.1;MS(EI)m/z(%):200(M ,20.99),73(100);IR(neat):v=2954,2916,‑1
2871,2848,1697,1470,1429,1411,1351,1328,1302,1277,1248,1220,1193,1084cm .[0181] 实施例42:环己基甲酸的合成
(115.4mg,90%)(石油醚:乙酸乙酯=5:1)。H NMR(400MHz,CDCl3)δ=11.43(brs,1H,COOH),2.33(tt,J=11.2,3.6Hz,1H,Ha),2.00‑1.88(m,2H,Hb),1.84‑1.70(m,2H,He),1.70‑
13
1.58(m,1H,Hf),1.55‑1.38(m,2H,Hc),1.37‑1.18(m,3H,Hd and Hg);C NMR(100MHz,+
CDCl3)δ=182.9,42.9,28.7,25.6,25.3;MS(EI)m/z(%):128(M ,53.29),55(100);IR‑1
(neat):v=2930,2855,1698,1451,1417,1311,1295,1256,1212,1182,1136,1021cm .[0184] 实施例43:辛酸的合成
酸(138.4mg,96%)(石油醚:乙酸乙酯=5:1)。H NMR(400MHz,CDCl3)δ11.33(brs,1H,COOH),2.35(t,J=7.4Hz,2H,CH2),1.63(quint,J=7.3Hz,2H,CH2),1.38‑1.22(m,8H,4×
13
CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ=180.6,34.1,31.6,29.0,28.9,+ ‑1
24.6,22.6,14.0;MS(EI)m/z(%):144(M ,2.09),60(100);IR(neat,cm )=2956,2925,‑1
2857,1706,1459,1412,1379,1275,1230,1203,1108cm .
时间为12小时,得到苯丙酸(144.9mg,96%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ11.56(brs,1H,COOH),7.32‑7.25(m,2H,Ar‑H),7.23‑7.16(m,2H,Ar‑H),
13
2.95(t,J=7.8Hz,2H,CH2),2.67(t,J=7.8Hz,2H,CH2);C NMR(100MHz,CDCl3)δ179.6,+
140.1,128.5,128.2,126.3,35.6,30.5;MS(EI)m/z(%):150(M ,50.1),91(100);IR(neat,‑1 ‑1
cm )3030‑2620,1693,1602,1497,1448,1427,1407,1358,1300,1216,1158,1082cm .[0190] 实施例45:十二酸的合成
1
后,硅胶柱层析(石油醚:乙酸乙酯=5:1)纯化得到十二酸(176.5mg,88%)。H NMR
(400MHz,CDCl3)δ11.49(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),1.63(quint,J=7.3Hz,
13
2H,CH2),1.40‑1.18(m,16H,8×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ=180.5,34.1,31.9,29.6,29.4,29.3,29.2,29.0,24.6,22.7,14.1.
16小时,得到环己基甲酸(106.4mg,83%)(石油醚:乙酸乙酯=5:1)。H NMR(400MHz,CDCl3)δ=11.42(brs,1H,COOH),2.33(tt,J=11.2,3.6Hz,1H,Ha),2.00‑1.88(m,2H,Hb),1.84‑
1.70(m,2H,He),1.70‑1.60(m,1H,Hf),1.55‑1.38(m,2H,Hc),1.37‑1.18(m,3H,Hd and Hg)
13
;C NMR(100MHz,CDCl3)δ=182.9,42.9,28.7,25.6,25.3.
时,得到辛酸(139.7mg,97%)(石油醚:乙酸乙酯=5:1)。H NMR(400MHz,CDCl3)δ=11.02(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),1.63(quint,J=7.4Hz,2H,CH2),1.38‑1.18(m,
13
8H,4×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ=180.6,34.1,31.6,
29.0,28.9,24.6,22.6,14.0.
时间为16小时,得到苯丙酸(147.7mg,98%)(石油醚:乙酸乙酯=5:1到2:1)。H NMR(400MHz,CDCl3)δ11.09(brs,1H,COOH),7.32‑7.25(m,2H,Ar‑H),7.24‑7.17(m,2H,Ar‑H),
13
2.95(t,J=7.8Hz,2H,CH2),2.67(t,J=7.8Hz,2H,CH2);C NMR(100MHz,CDCl3)δ179.5,
140.1,128.5,128.2,126.3,35.6,30.5.
1
83%):H NMR(400MHz,CDCl3)δ3.67(s,3H,OMe),2.33(t,J=7.4Hz,2H,CH2),2.20(td,J1=
6.9Hz,J2=2.5Hz,2H,≡CCH2),1.95(t,J=2.6Hz,1H,≡CH),1.70‑1.60(m,2H,CH2),1.60‑
13
1.50(m,2H,CH2),1.49‑1.39(m,2H,CH2);C NMR(100MHz,CDCl3)δ174.0,84.2,68.3,51.4,‑1
33.8,28.1,28.0,24.3,18.1;IR(neat)ν(cm )3296,2943,2863,2117,1738,1460,1436,‑
1364,1325,1263,1205,1174,1145,1087,1071,1008.MS(ESI)m/z(%):155.1(M+1) .
30.6 1
22.1min);[α]D =‑36.8(c=1.015,CHCl3);H NMR(400MHz,CDCl3)δ5.11‑5.00(m,2H,CH=C=CH),3.66(s,3H,CH3),2.30(t,J=7.6Hz,2H,CH2),2.02‑1.93(m,4H,2×CH2),1.63
13
(quint,J=7.5Hz,2H,CH2),1.46‑1.20(m,22H,11×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ203.8,174.2,91.1,90.5,51.4,34.0,31.9,29.65,29.63,29.62,‑1
29.5,29.3,29.2,29.1,29.0,28.73,28.71,28.6,24.8,22.7,14.1;IR(neat)ν(cm )2923,+
2853,1962,1742,1462,1437,1362,1255,1199,1170,1087,1012;MS(EI)m/z(%)322(M ,+
6.73),150(100);HRMS calcd.for C21H38O2(M):322.2872;Found:322.2876.
1
到天然产物phlomic acid(283.6mg,92%)。H NMR(400MHz,CDCl3)δ11.7(brs,1H,COOH),
5.11‑5.01(m,2H,CH=C=CH),2.35(t,J=7.6Hz,2H,CH2),2.02‑1.93(m,4H,2×CH2),1.65
13
(quint,J=7.5Hz,2H,CH2),1.49‑1.20(m,22H,11×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ203.8,180.5,91.1,90.5,34.1,31.9,29.67,29.66,29.64,29.5,‑1
29.4,29.2,29.1,29.0,28.71,28.69,28.5,24.5,22.7,14.1;IR(neat)ν(cm )2915,2849,+
1964,1708,1683,1458,1415,1331,1285,1246,1200.MS(EI)m/z(%):308(M ,5.91),168+
(100);HRMS calcd.for C20H36O2(M):308.2715;Found:308.2717.
(major)=23.7min,tR(minor)=32.3min);[α]D =‑39.9(c=0.99,CHCl3);H NMR(400MHz,CDCl3)δ5.11‑5.01(m,2H,CH=C=CH),3.67(s,3H,CH3),2.36(t,J=7.6Hz,2H,CH2),2.03‑1.92(m,4H,2×CH2),1.63(quint,J=7.5Hz,2H,CH2),1.46‑1.20(m,22H,11×
13
CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ203.8,174.2,91.1,90.6,51.4,
34.0,31.9,29.66,29.63,29.5,29.3,29.2,29.1,29.0,28.73,28.71,28.6,24.8,22.7,
14.1.
1
作内标,核磁定量氢谱(H NMR)测得十二酸的产率为78%,十二过氧酸的产率为11%。该粗产品通过硅胶柱层析(石油醚:乙酸乙酯=20:1到5:1)得到十二酸和十二过氧酸。十二酸:
1
H NMR(400MHz,CDCl3)δ11.49(brs,1H,COOH),2.35(t,J=7.6Hz,2H,CH2),1.63(quint,J=
13
7.2Hz,2H,CH2),1.38‑1.21(m,16H,8×CH2),0.88(t,J=6.6Hz,3H,CH3);C NMR(100MHz,
1
CDCl3)δ=180.6,34.1,31.9,29.6,29.4,29.3,29.2,29.0,24.6,22.7,14.1.十二过氧酸:H NMR(400MHz,CDCl3)δ11.38(brs,1H,CO3H),2.42(t,J=7.6Hz,2H,CH2),1.70(quint,J=
13
7.3Hz,2H,CH2),1.39‑1.19(m,16H,8×CH2),0.88(t,J=6.8Hz,3H,CH3);C NMR(100MHz,CDCl3)δ=174.7,31.9,30.4,29.54,29.51,29.32,29.29,29.0,28.9,24.6,22.7,14.1.