A practical synthesis of 2,3-dihydro-1,5-benzothiazepines

A practical synthesis of 2,3-dihydro-1,5-benzothiazepines

Green Chem., 2017, 19,5703-5707
DOI: 10.1039/C7GC02097J, Paper

Domenico C. M. Albanese, Nicoletta Gaggero, Meng Fei
Hexafluoro-2-propanol as the solvent allows a catalyst free domino approach to 2,3-dihydro-1,5-benzothiazepines in up to 98% yield.

 

A practical synthesis of 2,3-dihydro-1,5-benzothiazepines

 

Domenico C. M. Albanese,^a  Nicoletta Gaggero*^b  and  Meng Fei^b 

*Corresponding authors

^aDepartment of Chemistry, Università degli Studi di Milano, via C. Golgi 19, Milano, Italy

^bDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, via L. Mangiagalli 25, Milano, Italy
E-mail:nicoletta.gaggero@unimi.it

Domenico C. M. Albanese

University of Milan

LocationMilano, Italy

DepartmentDepartment of Chemistry

Positionassociate professor

Domenico Albanese received his Ph.D. degree in 1993 with Prof. Dario Landini working on phase transfer catalysis. After short stays at Imperial College London and the Technical University of Denmark, he gained a permanent position at the Università degli Studi di Milano, where he was appointed associate professor in 2008. His research interests include novel developments of phase-transfer catalysis, green chemistry and the development of new environmentally friendly antifouling agents.

Nicoletta Gaggero

Nicoletta Gaggero received her Ph.D. degree in 1992 working on stereoselective reactions with natural proteins, enzymes and models of enzymes. After working at the Laboratoire de Chimie de Coordination du CNRS of Toulouse, she obtained a permanent position at the Università degli Studi di Milano. Her research interests cover the field of biocatalysis and asymmetric synthesis.

Abstract

2,3-Dihydro-1,5-benzothiazepines have been obtained through a domino process involving a Michael addition of 2-aminothiophenols to chalcones, followed by in situ cyclization. Up to 98% chemical yields have been obtained at room temperature under essentially neutral conditions by using hexafluoro-2-propanol as an efficient medium.
http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02097J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

 

 

2,4-Diphenyl-2,3-dihydro-1,5-benzothiazepine (4a)

 

Yellow solid; mp 114-116 C [lit.1 , 114-115 °C], AcOEt/PE 1:9. 1H NMR (300 MHz, CDCl3,): 3.07 (t, J = 12.6 Hz, 1 H), 3.32 (dd, J = 4.7, 13.1 Hz, 1 H), 4.99 (dd, J = 4.5, 12.0 Hz, 1 H), 7.12-7.17 (m, 1 H), 7.25-7.30 (m, 5 H), 7.44-7.51 (m, 4 H), 7.62 (d, J = 6.1 Hz, 2 H), 8.06 (d, J = 7.5 Hz, 2 H). Isolated Yield: 339 mg, 86%.

 

2-(4-Hydroxyphenyl)-4-phenyl-2,3-dihydro-1,5-benzothiazepine (4e)

Light brown solid; mp 131-134 °C. AcOEt/PE 40:60.

1H NMR (CDCl3, 300 MHz):  = 3.01 (t, J = 12.7 Hz, 1 H), 3.28 (dd, J = 4.8, 12.9 Hz, 1 H), 4.95 (dd, J = 4.7, 12.5 Hz, 1 H), 5.10 (bs, 1 H), 6.76 (d, J = 8.5 Hz, 2 H), 7.18-7.21 (m, 3 H), 7.35 (d, J = 8.5 Hz, 1 H), 7.46- 7.55 (m, 4 H), 7.63 (dd, J =1.5, 7.7 Hz, 1 H), 8.06 (m, 2 H).

13C NMR (CDCl3, 75 MHz): 37.99 (CH2), 60.07 (CH), 115.53 (CH), 123.08 (C), 127.40 (CH), 128.79 (CH), 131.17 (CH), 136.54 (C), 141.59 (C), 155.24 (C). IR (KBr): 1599, 2921, 3350 cm-1 .

MS (ESI): m/z= 332.24 (MH)+ .

Anal. Calcd. for C21H17NOS: C, 76.10; H, 5.17; N, 4.23, found: C, 76.21; H, 5.15; N, 4.24.

Isolated Yield: 360 mg, 87%.

 

 

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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Ruthenium-Catalyzed Tandem C–H Fluoromethylation/Cyclization of N-Alkylhydrazones with CBr3F: Access to 4-Fluoropyrazoles

4-Fluoropyrazoles are accessible in a single step from readily available aldehyde-derived N-alkylhydrazones through double C–H fluoroalkylation with tribromofluoromethane (CBr3F). RuCl2(PPh3)3 has been proven to be the most efficient catalyst for this transformation when compared to a range of other Cu-, Pd-, or Fe-based catalyst systems.

Alexis Prieto

Alexis Prieto, Didier Bouyssi*, and Nuno Monteiro* 

Univ Lyon, Université Claude Bernard Lyon 1, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS, CNRS UMR 5246), F-69622 Villeurbanne, France

J. Org. Chem., 2017, 82 (6), pp 3311–3316

DOI: 10.1021/acs.joc.7b00085

*E-mail: didier.bouyssi@univ-lyon1.fr., *E-mail: nuno.monteiro@univ-lyon1.fr.

Ruthenium-Catalyzed Tandem C–H Fluoromethylation/Cyclization of N-Alkylhydrazones with CF3BR: Access to 4-Fluoropyrazoles

http://pubs.acs.org/doi/10.1021/acs.joc.7b00085

---

The importance of fluorine-containing pyrazoles to the pharmaceutical and agrochemical industries has been steadily increasing in recent years. As a consequence, the development of methods suitable for the incorporation of fluorine or fluoroalkyl groups into the pyrazole ring continues to be the subject of intense research.

Predicated on their previous copper-catalyzed synthesis of 4-substituted pyrazoles, Bouyssi, Monteiro and their co-worker from the Institut de Chemie et Biochemie Moléculaires et Supramoléculaires reported a ruthenium-catalyzed synthesis of substituted-4-fluoropyrazoles ( J. Org. Chem. 2017, 82, 3311). The requisite starting materials, aldehyde derived N,N-dialkylhydrazones, were readily synthesized. Tribromofluoromethane served as the source of fluorine.

The commercially available and inexpensive ruthenium complex, RuCl2(PPh3)3, was discovered to be a very effective catalyst for this transformation. Diglyme was the preferred solvent for the reaction. The reaction displayed good tolerance for a variety of functional groups, including cyano, ester, formyl, and halide.

In general, higher yields were obtained with electron-withdrawing substituents. This novel methodology affords substituted-4-fluoropyrazoles in good yields in one step from readily available starting materials.

                                                 2K

3-(Benzo[d][1,3]dioxol-5-yl)-4-fluoro-1-methyl-1H-pyrazole (2k)

Chromatography using ethyl acetate/cyclohexane (gradient elution 30:70 to 50:50) gave the title compound as a pale yellow solid (79 mg, 60%).

Mp = 82–85 °C.

1H NMR (400 MHz, CDCl3) δ 7.35–7.31 (m, 2H), 7.27 (d, J = 4.8 Hz, 1H), 6.85 (d, J = 8.5 Hz, 1H), 5.97 (s, 2H), 3.83 (s, 3H).

13C NMR (101 MHz, CDCl3) δ 148.0, 147.2, 146.8 (d, J = 248.0 Hz), 136.7 (d, J = 6.2 Hz), 125.3 (d, J = 4.2 Hz), 119.8 (d, J = 4.7 Hz), 117.5 (d, J = 28.6 Hz), 108.6, 106.6 (d, J = 3.7 Hz), 101.1, 40.0 (s).

19F NMR (282 MHz, CDCl3) δ −178.2 (s). HRMS (ESI): Calcd for C11H10FN2O2 [M + H+]: 221.0721, found 221.0728.

Alexis prieto

Chercheur postdoctoral chez Melchiorre group, ICIQ

Melchiorre group, ICIQ

Didier Bouyssi

Univ Lyon, Université Claude Bernard Lyon 1, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS, CNRS UMR 5246), F-69622 Villeurbanne, France

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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Continuous-Flow Preparation of γ-Butyrolactone Scaffolds, 2-(5,5-dimethyl-2-oxotetrahydrofuran-3- yl)acetic acid

(5,5-dimethyl-2-oxotetrahydrofuran-3-yl)acetic acid

2-(5,5-Dimethyl-2-oxotetrahydrofuran-3-yl)acetic acid

2-carboxymethyl-4-methyl-4-pentanolide,

Cas 412298-86-3

2-(5,5-Dimethyl-2-oxotetrahydrofuran-3-yl)acetic acid (4a).

1H NMR (DMSO-d6, 400 MHz): δ = 3.20 – 3.10 (m, 1H), 2.62 (dd, J = 17.1, 4.4 Hz, 1H), 2.54 – 2.45 (m, 1H), 2.31 – 2.21 (m, 1H), 1.84 (t, J = 12.0 Hz, 1H), 1.39 (s, 3H), 1.33 (s, 3H) ppm.

13C NMR (DMSO-d6, 100.6 MHz): δ = 177.2, 172.5, 82.2, 39.8, 36.7, 34.0, 28.4, 26.6 ppm.

The 1H NMR data did not match those reported in the literature. S7 IR (neat): νmax = 2980, 2935, 1728, 1707 cm- 1 .

MP: 132.1-133.8 °C (lit.S8 137-140 °C).

[S7] Kochikyan, T. V.; Arutyunyan, E. V.; Arutyunyan, V. S.; Avetisyan, A. A. Russ. J. Org. Chem. 2002, 38, 390–393.

[S8] Phillips, D. D.; Johnson, W. A. J. Am. Chem. Soc. 1955, 77, 5977–5982.

ESI HRMS m/z C8H11O4 - [M-H]- : calcd 171.0652. Found 171.0653.

Continuous-Flow Preparation of γ-Butyrolactone Scaffolds from Renewable Fumaric and Itaconic Acids under Photosensitized Conditions

Romaric Gérardy†, Marc Winter‡, Clemens R. Horn‡, Alessandra Vizza‡, Kristof Van Hecke§, and Jean-Christophe M. Monbaliu*† 

† Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, B-4000 Liège (Sart Tilman), Belgium

‡ Corning Reactor Technologies, Corning SAS, 7 bis Avenue de Valvins, CS 70156 Samois sur Seine, 77215 Avon Cedex, France

§ XStruct, Department of Chemistry, Ghent University, Krijgslaan 281-S3, B-9000 Ghent, Belgium

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00314

 

*E-mail: jc.monbaliu@ulg.ac.be.

Abstract

The method and results described herein concern the photosensitized addition of various alcohols to renewable platform fumaric and itaconic acids under scalable continuous-flow conditions in glass micro- and mesofluidic reactors. Alcohols were used both as reagents and as solvents, thus contributing to a reduced environmental footprint. Process parameters such as the temperature, light intensity, and the nature as well as amount of the photosensitizer were assessed under microfluidic conditions and, next, transposed to a lab-scale mesofluidic reactor connected with an in-line NMR spectrometer for real-time reaction monitoring. Substituted γ-butyrolactones, including spiro derivatives with unique structural features, were obtained with quantitative conversion of the starting materials and in 47–76% isolated yields. The model photoaddition of isopropanol to fumaric acid was next successfully transposed in a pilot-scale continuous-flow photoreactor to further demonstrate scalability.

JC M. Monbaliu, PhD.
Department of Chemistryjc.monbaliu@ulg.ac.be
t +32 (0) 4 366 35 10

Jean-Christophe M. Monbaliu*† 

† Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, B-4000 Liège (Sart Tilman), Belgium

Romaric Gérardy

PhD Student at Université de Liège

Center for Integrated Technology and Organic Synthesis (CiTOS)

 Université de Liège, Liège Area, Belgium

 

Kristof Van Hecke

XStruct, Department of Chemistry, Ghent University, Krijgslaan 281-S3, B-9000 Ghent, Belgium

Kristof.VanHecke@UGent.be

Group leader of the XStruct group

Alessandra Vizza

Corning Reactor Technologies, Corning SAS, 7 bis Avenue de Valvins, CS 70156 Samois sur Seine, 77215 Avon Cedex, France

Marc Winter

Senior Application Engineer - Advanced-Flow(tm) Reactors

CorningFontainebleau, France

Corning Reactor Technologies, Corning SAS, 7 bis Avenue de Valvins, CS 70156 Samois sur Seine, 77215 Avon Cedex, France

Clemens R. Horn

Clemens Horn, Senior Research Scientist

Corning SAS

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2,4-dimorpholinocyclopent-2-enone

1465003-25-1 cas

2,4-dimorpholinocyclopent-2-enone (1b):

1H NMR (300 MHz, CDCl3) 6.24 (d, J = 2.9 Hz, 1H, COC=CH), 3.78 (t, J = 4.7 Hz, 4H, morpholine), 3.73 (t, J = 4.7 Hz, 4H, morpholine), 3.73-3.72 (m, 1H, COCH2CHN), 3.15-3.14 (m, 4H, morpholine), 2.54-2.52 (m, 4H, morpholine), 2.49-2.48 (m, 1H, COCH2), 2.46-2.45 (m, 1H, COCH2);

13C NMR (75 MHz, CDCl3) 38.1, 48.1, 50.0, 60.3, 66.6, 67.1, 129.5, 151.7, 202.0.

Water excellent solvent for the synthesis of bifunctionalized cyclopentenones from furfural

M. Nardi,*ab  P. Costanzo,c  A. De Nino,a  M. L. Di Gioia,d  F. Olivito,c  G. Sindonaa  and  A. Procopioc 

*Corresponding authors

aDipartimento di Chimica, Università della Calabria, Cubo 12C, 87036-Arcavacata di Rende, Italy
E-mail: monica.nardi@unical.it
Fax: +39 0984493307
Tel: +39 0984 492850

bDipartimento di Agraria, Università Telematica San Raffaele, 247, Roma Via di Val Cannuta, Italy

cDipartimento di Scienze della Salute, Università Magna Graecia, Viale Europa, 88100-Germaneto, Italy

dDipartimento di Farmacia e Scienze della Salute e della Nutrizione, Edificio Polifunzionale, Università della Calabria, 87030 Arcavacata di Rende, Italy

Abstract

Chiral cyclopentenones are important precursors in the asymmetric synthesis of target molecules. In particular, C-2 amino cyclopentenones could be utilised as intermediates towards antitumor natural products. On the basis of our previous experience, we report an environmentally friendly protocol for the synthesis of bifunctionalized cyclopentenones in water from furfural. The use of water and MW gives high regioselectivity and good to excellent yields. The reaction can be realized in short times with various nucleophiles.

Monica Nardi

PostDoc

Università della Calabria , Rende · Dipartimento di Chimica e Tecnologie Chimiche - CTC

Università della Calabria

Department

• Dipartimento di Chimica e Tecnologie Chimiche - CTC

• Research experience

  • Oct 2014–present

    Visiting Lectur

    The School of Pharmacy · School of Pharmacy · Prof Steve Brocchini
    United Kingdom · London
  • Jan 2014–present

    PostDoc Position

    Università della Calabria · Department of Pharmacy, Health and Nutritional Sciences
    Italy · Rende
  • Mar 2001–Sep 2014

    PostDoc

    Università della Calabria · Department of Management
    Italy · Rende
  • Mar 2001–Dec 2013

    PostDoc Position

    Università della Calabria · Dipartimento di Chimica e Tecnologie Chimiche - CTC · Prof Giovanni Sindona
    Italy · Rende

Dipartimento di Chimica, Università della Calabria

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1 Estevão, Mónica S.; Afonso, Carlos A.M.; Tetrahedron Letters; vol. 58; nb. 4; (2017); p. 302 - 304

2  Green Chemistry; vol. 19; nb. 1; (2017); p. 164 - 168



“ORG SPECT INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Ethyl(E)-3-(4-methoxyphenyl)acrylate

ethyl(E)-3-(4-methoxyphenyl)acrylate (Table 4, entry 3):

The product was purified with column chromatography on silica gel 60-120 mesh (hexane/ethyl acetate= 9:1) as a white solid; yield 88 % (165 mg);

mp 74-76C;

1H NMR (CDCl3 , 200 MHz):  7.55 (d, 1H, J=15.9 Hz), 7.40-7.43 (d, 2H, J=6 Hz), 6.81-6.84 (d, 2H, J=6 Hz), 6.21 (d, 1H, J=15.9 Hz), 4.16 (q, 2H, J=7.1 Hz), 3.73 (s, 3 H), 1.24 (t, 3H, J=7.1 Hz);

13C NMR (CDCl3 , 50 MHz): 167.3, 161.3, 144.2, 129.7, 127.7, 127.2, 115.8, 114.3, 60.3, 55.3, 14.4 ppm;

MS (ESI) C12H14O3 : m/z 206.

(E)-ethyl 3-(4-methoxyphenyl)acrylate

13C NMR PREDICT

An Efficient Palladium Catalyzed Mizoroki-Heck Cross-Coupling in Water

Green Chem., 2017, Accepted Manuscript
DOI: 10.1039/C7GC02869E, Paper

Sanjay Jadhav, C. V. Rode
The homogeneous Pd-catalysed Mizoroki-Heck coupling reaction has been successfully conducted in water in the absence of any additives under aerobic condition. The various key reaction parameters that affect the yield...

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“ORG SPECT INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Problem, [(E)-hex-2-en-2-yl]benzene

Molecular Formula:	C12H16
Molecular Weight:	160.26 g/mol

 [(E)-hex-2-en-2-yl]benzene

NMR IS EASY

MOM CAN TEACH

13 CNMRPREDICT

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CC(C)c1ccc(cc1CC(=O)O)C=O

“ORG SPECT INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent


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C/C(=C\CCC)c1ccccc1