Page 222 - 《精细化工》2022年第6期

·1288· 精细化工 FINE CHEMICALS 第 39 卷

脱氢芳构化过程最初的投料量是 1.5 g（中间体Ⅱ）， 参考文献：
产物收率为 70%，将投料量放大至 100 g，产物收率 [1] YANG L, HUANG Z Y, LIU G, et al. Synthesis of phenols:
约为 62%。整个工艺放大前的总收率为 66%，放大 Organophotoredox/nickel dual catalytic hydroxylation of aryl halides
with water[J]. Angewandte Chemie International Edition, 2007, 1:
后的总收率约为 52%。 45-50.
从反应结果来看，整个反应过程产物的收率都 [2] ZANG Y L (臧阳陵), XU J B (徐建兵), YANG Y Q (阳永强), et al.
Synthesis of 4-(sec-butyl)-2,6-di-tert-butylphenol[J]. Fine Chemicals
有所下降。Robinson 环合过程可能是由于搅拌效果 (精细化工), 2012, 29(1): 70-72.
不佳或者冷凝效果不佳使乙醛在高温下挥发较多， [3] XIU J H (修景海), GE P Y (葛培元), CHEN F Y (陈福元), et al.
Research on the synthesis of 2,5-xylenol[J]. Fine Chemicals (精细化
从而导致产物收率降低；皂化脱羧过程和脱氢芳构
工), 1998, 15(1): 47-49.
化过程可能是由于反应时间较短或者搅拌效果不佳 [4] LIU L X, LI Z G, CHEN C J, et al. Efficient dealkylation of aryl
导致目标产物收率下降。此工艺存在一定的放大效 alkyl ethers catalyzed by Cu 2O[J]. Tetrahedron, 2018, 74(20): 2447-
2453.
应，还需进一步优化。 [5] GUALANDI A, SAVOINI A, SAPORETTI R, et al. A facile
2.7 3-甲基-5-丙基苯酚的合成 hydroxylation of arylboronic acids mediated by sodium ascorbate[J].
Organic Chemistry Frontiers, 2018, 5(10): 1573-1578.
基于环己烯酮脱氢芳构化法合成 3,5-二甲基苯 [6] MISAL B, PALAV A, GANWIR P, et al. Activator free, expeditious
酚具有选择性好、收率高等优势。本文进一步将该 and eco-friendly chlorination of activated arenes by N-chloro-N-
(phenylsulfonyl)benzene sulfonamide (NCBSI)[J]. Tetrahedron Letters,
工艺应用于另一种酚类物质即 3-甲基-5-丙基苯酚的
2021, 63: 152689.
合成，如图 8 所示。 [7] DEGANI I, FOCHI R, MAGISTRIS C. An easy and efficient
one-step procedure for the preparation of alkyl and aryl
alkylcarbamates from S-methyl N-alkylthiocarbamates[J]. Synthesis,
2008, 18: 2919-2924.
[8] BERSET J D, KREBS A. Synthesis and characterization of new
10-acylderivatives of the antipsoriatic agent dithranol: Coupling
products of dithranol with all-trans-retinoic acid, 13-cis-retinoid acid
and an aromatic analogue of retinoic acid: All-trans-9-(4-methoxy-
2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoate[J].
Pharmaceutica Acta Helvetiae, 1990, 11: 290-297.
[9] QIAN J L, YI W B, HUANG X, et al. One-pot synthesis of 3,
5-disubstituted and polysubstituted phenols from acyclic
precursors[J]. Organic Letters, 2015, 17(5): 1090-1093.
图 8 3-甲基-5-丙基苯酚的合成路线 [10] XU K X (徐克勋). Manual of fine organic chemical raw materials
Fig. 8 Synthetic route of 3-methyl-5-propylphenol and intermediates[M]. Beijing: Chemical Industry Press (化学工业
出版社), 1997.
3-甲基-5-丙基苯酚也是一种重要的精细化工原 [11] YAMAURA T, KAMATA K, YAMAGUCHI K, et al. Efficient
料和有机合成中间体。在同样条件下，乙酰乙酸乙 sulfoxidation with hydrogen peroxide catalyzed by a divanadium-
substituted phosphotungstate[J]. Catalysis Today, 2013, 203: 76-80.
酯和正丁醛的 Robinson 环合过程收率为 75%，最终 [12] CHEN F, LI N, WANG W T, et al. Catalytic conversion of
目标产物 3-甲基-5-丙基苯酚的收率为 68%，表明此 isophorone to jet-fuel range aromatic hydrocarbons over a
MoO x/SiO 2 catalyst[J]. Chemical Communications, 2015, 51(59):
法具有一定的普适性。
11876-11879.
[13] LIU Y X, SUN K P, MA H W, et al. Cr, Zr-incorporated hydrotalcites
3 结论 and their application in the synthesis of isophorone[J]. Catalysis
Communications, 2010, 11(10): 880-883.
建立了简单高效的 3,5-二甲基苯酚的合成工 [14] KIRICHENKO G N, GLAZUNOVA V I, KIRICHENKO V Y, et al.
Promising process for synthesis of 3,5-xylenol from isophorone[J].
艺。以乙酰乙酸乙酯和乙醛为原料，经过 Robinson Petroleum Chemistry, 2006, 46(6): 434-438.
环合、皂化脱羧以及脱氢芳构化反应，成功得到了 [15] ZHANG X, WANG R J, YANG X X, et al. Central composite
experimental design applied to the catalytic aromatization of
目标产物 3,5-二甲基苯酚。 isophorone to 3,5-xylenol[J]. Chemometrics & Intelligent Laboratory
通过对乙酰乙酸乙酯和乙醛的 Robinson 环合反 Systems, 2007, 89(1): 45-50.
[16] BI X H, DONG D W, LIU Q, et al. [5+1]Annulation: A synthetic
应的系统研究，发现碱催化剂的碱性对此环合反应
strategy for highly substituted phenols and cyclohexenones[J].
影响很大，筛选得到的无水碳酸钠催化体系能使乙 Journal of American Chemical Society, 2005, 127(13): 4578-4579.
酰乙酸乙酯和乙醛的 Robinson 环合反应高效进行， [17] HEGDE S G, KASSIM A M, KENNEDY A I. Aromatization
reactions of 2-cyclohexenones and 1,3-cyclohexadien-1-amines with
有效地避免了乙酰乙酸乙酯和乙醛的自身缩合，最 iodine/sodium alkoxide[J]. Tetrahedron, 2001, 57(9): 1689-1698.
终以 95%的收率得到 4-乙氧羰基-3,5-二甲基-2-环己 [18] CHONG B D, JI Y, OH S S, et al. Highly efficient synthesis of
methyl-substituted conjugate cyclohexenones[J]. Journal of Organic
烯-1-酮。 Chemistry, 1997, 62(26): 9323-9325.
该方法也以较高收率成功用于 3-甲基-5-丙基 [19] WILLIAMS R V, GADGIL V R, VIJ A, et al. Unexpected
stereoselectivity in the Weiss-Cook condensation of dimethyl 1,
苯酚的合成。 3-acetonedicarboxylate with pentane-2,3-dione[J]. Journal of the