A monolithic 5-(pyrrolidin-2-yl)tetrazole flow microreactor for the asymmetric aldol reaction in water-ethanol solvent

被引：21

作者：

Greco, Roberto ^{[1
]}

Caciolli, Lorenzo ^{[1
]}

Zaghi, Anna ^{[1
]}

Pandoli, Omar ^{[2
]}

Bortolini, Olga ^{[1
]}

Cavazzini, Alberto ^{[1
]}

De Risi, Carmela ^{[1
]}

Massi, Alessandro ^{[1
]}

机构：

[1] Univ Ferrara, Dipartimento Sci Chim & Farmaceut, Via Fossato Mortara 17, I-44121 Ferrara, Italy

[2] Pontificia Univ Catolica Rio de Janeiro, Dept Quim, Rua Marques de Sao Vincente 225, BR-22451900 Rio de Janeiro, Brazil

来源：

REACTION CHEMISTRY & ENGINEERING | 2016年 / 1卷 / 02期

关键词：

PHASE LIQUID-CHROMATOGRAPHY; ORGANOCATALYTIC ROUTE; CARBONYL-COMPOUNDS; ORGANIC-SYNTHESIS; PROLINE; CHEMISTRY; CATALYSTS; TETRAZOLE; MICHAEL; MANNICH;

D O I：

10.1039/c5re00017c

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

An (S)-5-(pyrrolidin-2-yl)-1H-tetrazole organocatalyst has been prepared in the form of a monolithic column through the radical copolymerization of a styryl-functionalized pyrrolidinyl-tetrazole derivative, styrene and divinylbenzene in the presence of porogens (dodecanol and toluene). The activity of the monolithic pyrrolidinyl-tetrazole organocatalyst (triturated polymer) has been initially tested under batch conditions using the asymmetric aldol reaction of cyclohexanone and p-nitrobenzaldehyde as the benchmark. A prerequisite of the study has been the utilization of the eco-friendly water-ethanol mixture as the solvent. After having established the high efficiency and recyclability of the catalyst under these conditions, the effect of the flow regime has been evaluated by fabricating the corresponding monolithic microreactor (pressure-resistant stainless steel column). It has been demonstrated by a brief substrate scope study that the flow regime contributes to preserve the activity of the pyrrolidinyl-tetrazole catalyst over time (5 days on stream) with an almost twofold increase in productivity moving from batch to flow conditions. An added value of the flow procedure has been the optimization of a suitable 2D instrumental setup for simultaneous flow reaction and online flow-injection analysis.

引用

页码：183 / 193

页数：11

共 60 条

[21] Reversal of the enantioselectivity in aldol addition over immobilized di- and tripeptides: studies under continuous flow conditions [J].

Gurka, Andras ;

Bucsi, Imre ;

Kovacs, Lenke ;

Szollosi, Gyorgy ;

Bartok, Mihaly .

RSC ADVANCES, 2014, 4 (106) :61611-61618

[22] 5-(Pyrrolidine-2-yl)tetrazole: Rationale for the increased reactivity of the tetrazole analogue of proline in organocatalyzed aldol reactions [J].

Hartikka, A ;

Arvidsson, PI .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2005, 2005 (20) :4287-4295

[23] Rational design of asymmetric organocatalysts - increased reactivity and solvent scope with a tetrazolic acid [J].

Hartikka, A ;

Arvidsson, PI .

TETRAHEDRON-ASYMMETRY, 2004, 15 (12) :1831-1834

[24] The application of monoliths for gas phase catalytic reactions [J].

Heck, RM ;

Gulati, S ;

Farrauto, RJ .

CHEMICAL ENGINEERING JOURNAL, 2001, 82 (1-3) :149-156

[25] Novel Process Windows for Enabling, Accelerating, and Uplifting Flow Chemistry [J].

Hessel, Volker ;

Kralisch, Dana ;

Kockmann, Norbert ;

Noel, Timothy ;

Wang, Qi .

CHEMSUSCHEM, 2013, 6 (05) :746-789

[26]

Hutchings MJ, 2013, MICROREACTORS IN ORGANIC CHEMISTRY AND CATALYSIS, 2ND EDITION, P197

[27] A "Catch-React-Release" Method for the Flow Synthesis of 2-Aminopyrimidines and Preparation of the Imatinib Base [J].

Ingham, Richard J. ;

Riva, Elena ;

Nikbin, Nikzad ;

Baxendale, Ian R. ;

Ley, Steven V. .

ORGANIC LETTERS, 2012, 14 (15) :3920-3923

[28] Continuous flow techniques in organic synthesis [J].

Jas, G ;

Kirschning, A .

CHEMISTRY-A EUROPEAN JOURNAL, 2003, 9 (23) :5708-5723

[29] A sequential enantioselective, organocatalytic route to chiral 1,2-oxazines and chiral pyridazines [J].

Kumarn, Sirirat ;

Oelke, Alexander J. ;

Shaw, David M. ;

Longbottom, Deborah A. ;

Ley, Steven V. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2007, 5 (16) :2678-2689

[30] Oxidation Reactions in Segmented and Continuous Flow Chemical Processing Using an N-(tert-Butyl)phenylsulfinimidoyl Chloride Monolith [J].

Lange, Heiko ;

Capener, Matthew J. ;

Jones, Alexander X. ;

Smith, Catherine J. ;

Nikbin, Nikzad ;

Baxendale, Ian R. ;

Ley, Steven V. .

SYNLETT, 2011, (06) :869-873

← 1 2 3 4 5 6 →