A Fully Continuous-Flow Process for the Synthesis of p-Cresol: Impurity Analysis and Process Optimization

PROCESS, spectroscopy, SYNTHESIS Comments Off

Oct 092017

Abstract Image

A fully continuous-flow diazotization–hydrolysis protocol has been developed for the preparation of p-cresol. This process started from the diazotization of p-toluidine to form diazonium intermediate. The reaction was then quenched by urea and subsequently followed by a hydrolysis to give the final product p-cresol. Three types of byproducts were initially found in this reaction sequence. After an optimization of reaction conditions (based on impurity analysis), side reactions were eminently inhibited, and a total yield up to 91% were ultimately obtained with a productivity of 388 g/h. The continuous-flow methodology was used to avoid accumulation of the highly energetic and potentially explosive diazonium salt to realize the safe preparation for p-cresol.

. ¹H NMR (400 MHz, (CD₃)₂SO) δ/ppm: 9.06 (br s, 1H, −OH), 6.94 (d, J = 8.0 Hz, 2H, Ar–H), 6.62 (d, J = 8.0 Hz, 2H, Ar–H), 2.17 (s, 3H, −CH₃).

¹³C NMR (CDCl₃) δ/ppm: 153.0, 129.9, 115.1, 20.5.

Literature data:(3b) ¹H NMR (300 MHz, CDCl₃) δ/ppm: 7.03 (d, J = 8.2 Hz, 2H), 6.73 (dd, J = 8.2, 2.0 Hz, 2H), 4.75 (s, 1H, OH), 2.27 (s, 3H, CH₃).

¹³C NMR (CDCl₃) δ/ppm: 153.2, 130.2, 115.2, 20.6.

3(b) Taniguchi, T.; Imoto, M.; Takeda, M.; Nakai, T.; Mihara, M.; Iwai, T.; Ito, T.; Mizuno, T.; Nomoto, A.; Ogawa, A. Heteroat. Chem. 2015, 26, 411– 416 DOI: 10.1002/hc.21275

A Fully Continuous-Flow Process for the Synthesis of p-Cresol: Impurity Analysis and Process Optimization

Zhiqun Yu†, Xin Ye†, Qilin Xu‡, Xiaoxuan Xie†, Hei Dong†, and Weike Su^*†‡

^†National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, ^‡Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. China

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00250

*Tel.: (+86)57188320899. E-mail: pharmlab@zjut.edu.cn.

http://pubs.acs.org/doi/full/10.1021/acs.oprd.7b00250

NMR PREDICT

Total synthesis of natural products viairidium catalysis

SYNTHESIS Comments Off

Sep 292017

Total synthesis of natural products via iridium catalysis

Org. Chem. Front., 2017, Advance Article
DOI: 10.1039/C7QO00664K, Review Article

Changchun Yuan, Bo Liu
An overview of the highlights in total synthesis of natural products using iridium as a catalyst is given

http://pubs.rsc.org/en/Content/ArticleLanding/2017/QO/C7QO00664K#!divAbstract

Total synthesis of natural products viairidium catalysis

Changchun Yuan*^a and Bo Liu*^b

Author affiliations

*Corresponding authors

^aSchool of Chemical Engineering and Technology, North University of China, Taiyuan 030051, PR China
E-mail: ycc543700483@nuc.edu.cn

^bKey Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China
E-mail: chembliu@scu.edu.cn

Abstract

Catalysis with transition metals is a powerful synthetic tool for achieving a high degree of molecular complexity from relatively simple building blocks. Among these transition metals employed, iridium has attracted significant attention owing to its multifold roles in catalysis of various synthetically significant methodologies, and thus iridium catalysts are widely used in natural product synthesis. This review aims to comprehensively summarize recent accomplishments in total synthesis of natural products using iridium as the catalyst.

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School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, PR China

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Image result for College of Chemistry, Sichuan University, Chengdu Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu

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Catalyst-free multi-component cascade C-H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines

spectroscopy, SYNTHESIS Comments Off

Sep 202017

Catalyst-free multi-component cascade C-H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines

Green Chem., 2017, 19,4036-4042
DOI: 10.1039/C7GC01494E, Communication

Mohit L. Deb, Choitanya D. Pegu, Paran J. Borpatra, Prakash J. Saikia, Pranjal K. Baruah
Synthesis of 1,3-oxazines via catalyst free C-H functionalization using molecular oxygen in water.

Catalyst-free multi-component cascade C–H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines

Mohit L. Deb,*^a Choitanya D. Pegu,^a Paran J. Borpatra,^a Prakash J. Saikia^b and Pranjal K. Baruah*^a

Author affiliations

*Corresponding authors

^aDepartment of Applied Sciences, GUIST, Gauhati University, Guwahati-781014, India
E-mail: mohitdd.deb@gmail.com, baruah.pranjal@gmail.com
Fax: +91-8876998905
Tel: +91-8876998905

^bAnalytical chemistry division, CSIR-NEIST, Jorhat-785006, India

Abstract

Herein, catalyst-free 3-component reactions of naphthols, aldehydes, and tetrahydroisoquinolines to synthesize 1,3-oxazines is reported. The reaction is performed in H₂O in the presence of O₂ as the sole oxidant at 100 °C, which proceeds through the formation of 1-aminoalkyl-2-naphthols followed by selective α-C–H functionalization of tert-amine.

15-phenyl-7a,12,13,15-tetrahydronaphtho[1′,2′:5,6][1,3]oxazino[2,3- a]isoquinoline (4a):1

White solid; Yield 61 %, 221 mg;

1H NMR (500 MHz, CDCl3): δ 7.79-7.77 (m, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.43-7.41 (m, 1H), 7.33-7.28 (m, 8H), 7.24-7.19 (m, 3H), 7.11 (d, J = 8.9 Hz, 1H), 5.65 (s, 1H), 5.44 (s, 1H), 3.40-3.26 (m, 2H), 3.12-3.09 (m, 1H), 2.90- 2.86 (m, 1H);

13C NMR (125 MHz, CDCl3): δ 151.9, 142.3, 135.0, 133.0, 132.4, 129.3, 129.1, 128.9, 128.8 (2C), 128.7, 128.6, 128.2, 127.4, 126.5, 126.2, 123.1, 122.7, 118.9, 110.9, 82.2, 62.6, 45.4, 29.4;

HRMS (ESI) exact mass calculated for C26H21NO [M+H]+ : 364.1701; found: 364.1705.

The representative procedure for the synthesis of 4a is as follows: 2-naphthol (1a, 144 mg, 1 mmol), benzaldehyde (2a, 106 mg, 1 mmol), tetrahydroisoquinoline (3, 133 mg, 1 mmol) and water (1.5 mL) were added in a round-bottom flask equipped with a magnetic stirring bar and a reflux condenser. The whole apparatus was efficiently flushed with oxygen gas and then connected to a balloon filled with oxygen. After vigorous stirring at 100 oC for 12 h, water was removed under vacuum and purified the reaction mixture by column chromatography (100-200 mesh silica gel, hexane-ethyl acetate) to obtain the product 4a as white solid. The other 1,3-oxazines were synthesized and purified by following the procedure described above

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Efficient route for the construction of polycyclic systems from bioderived HMF

spectroscopy, SYNTHESIS Comments Off

Sep 162017

Efficient route for the construction of polycyclic systems from bioderived HMF

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02211E, Paper

F. A. Kucherov, K. I. Galkin, E. G. Gordeev, V. P. Ananikov
Efficient one-pot synthesis of tricyclic compounds from biobased 5-hydroxymethylfurfural (HMF) is described using a [4 + 2] cycloaddition reaction.

Efficient route for the construction of polycyclic systems from bioderived HMF

F. A. Kucherov,^a K. I. Galkin,^a E. G. Gordeev^a and V. P. Ananikov*^a

Author affiliations

*Corresponding authors

^aZelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky pr. 47, Moscow 119991, Russia
E-mail: val@ioc.ac.ru
Web: http://AnanikovLab.ru

Abstract

The first synthesis of tricyclic compounds from biobased 5-hydroxymethylfurfural (HMF) is described. The Diels–Alder reaction was used to implement the transition from HMF to a non-planar framework, which possessed structural cores of naturally occurring biologically active compounds and building blocks of advanced materials. A one-pot, three-step sustainable synthesis in water was developed starting directly from HMF. The reduction of HMF led to 2,5-bis(hydroxymethyl)furan (BHMF), which could be readily involved in the Diels–Alder cycloaddition reaction with HMF-derived maleimide, followed by hydrogenation of the double bond. The described transformation was diastereoselective and proceeded with a good overall yield. The applicability of the chosen approach for the synthesis of analogous structures containing amine functionality on the side chain was demonstrated. To produce the target compounds, only platform chemicals were used with carbohydrate biomass as the single carbon source.

Endo-4,7-bis(hydroxymethyl)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (endo-4,7-bis(hydroxymethyl)norcantharimid-5-ene), 3

1H NMR (DMSO-d6) = 10.82 (s, 1H), 6.37 (s, 2H), 5.11 (t, 2H, J = 5.7 Hz), 3.97 (dd, 2H, J = 5.7 Hz, 12.8 Hz), 3.84 (dd, 2H, J = 5.7 Hz, 12.8 Hz), 3.44 (s, 2H);

13C NMR (DMSO-d6) = 176.9, 136.0, 92.1, 59.8, 48.8 ppm.

m/z HRMS (ESI) Calcd. for C10H11NO5 [M+Na]: 248.0529. Found 248.0536.

STR7

1H NMR PREDICT

13C NMR PREDICT

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O=C1NC(=O)[C@H]3[C@@H]1[C@]2(C=C[C@]3(CO)O2)CO

Metal-free oxidative cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen

spectroscopy, SYNTHESIS Comments Off

Sep 072017

Metal-free oxidative cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02014G, Communication

Yanjun Xie, Xiangui Chen, Zhen Wang, Huawen Huang, Bing Yi, Guo-Jun Deng
Aerobic cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen under metal-free conditions.

Metal-free oxidative cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen

Yanjun Xie,^a^b Xiangui Chen,^a Zhen Wang,^a Huawen Huang,*^a Bing Yi*^b and Guo-Jun Deng*^a

*Corresponding authors

^aKey Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China
E-mail: hwhuang@xtu.edu.cn, gjdeng@xtu.edu.cn
Fax: (+86)0731-5829-2251
Tel: (+86)0731-5829-8601

^bCollege of Chemistry and Chemical Engineering, Hunan Institute of Engineering, Xiangtan 411104, China
E-mail: bingyi2004@126.com

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02014G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Abstract

Metal-free oxidative cyclization for the one-pot synthesis of benzo[d]imidazo[2,1-b]thiazoles from 2-aminobenzothiazoles and cyclic ketones is described. Elemental sulfur combined with molecular oxygen as the benign co-oxidant was found to be unique and highly effective to promote this transformation without the aid of any metal salts. Various cyclic ketones smoothly reacted with 2-aminobenzothiazoles to give functional benzo[d]imidazo[2,1-b]thiazoles in good to very high yields, which thereby demonstrated the synthetic convergence of this methodology.

7,8,9,10-Tetrahydrobenzo[d]benzo[4,5]imidazo[2,1-b]thiazole (3a)

White solid; yield: 39.2 mg (86%), mp 140-142 °C.

1H NMR (400 MHz, CDCl3, ppm) δ 7.67-7.62 (m, 2H), 7.38 (t, J = 7.76 Hz, 1H), 7.27 (t, J = 7.68 Hz, 1H), 3.07-3.04 (m, 2H), 2.77-2.74 (m, 2H), 2.00-1.95 (m, 2H), 1.92-1.86 (m, 2H);

13C NMR (100 MHz, CDCl3, ppm) δ 145.1, 142.4, 132.9, 129.7, 125.5, 123.9, 123.5, 121.8, 111.9, 24.8, 22.8, 22.7, 21.8;

MS (EI) m/z (%) 228, 200 (100), 160, 108, 51;

HRMS calcd. for: C13H13N2S + (M+H)+ 229.07940, found 229.07941.

PREDICT

cas 325766-28-7

C₁₃ H₁₂ N₂ S, 228.31, Benzimidazo[2,1-b]benzothiazole, 7,8,9,10-tetrahydro-

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C1CCCc2c1nc3sc4ccccc4n23

Route to Benzimidazol-2-ones via Decarbonylative Ring Contraction of Quinoxalinediones: Application to the Synthesis of Flibanserin, A Drug for Treating Hypoactive Sexual Desire Disorder in Women and Marine Natural Product Hunanamycin Analogue

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Sep 012017

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Route to Benzimidazol-2-ones via Decarbonylative Ring Contraction of Quinoxalinediones: Application to the Synthesis of Flibanserin, A Drug for Treating Hypoactive Sexual Desire Disorder in Women and Marine Natural Product Hunanamycin Analogue

Rahul D. Shingare^†^‡, Akshay S. Kulkarni^†, Revannath L. Sutar^†, and D. Srinivasa Reddy ^*^†^‡

^† Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India

^‡ Academy of Scientific and Innovative Research (AcSIR), New Delhi 110 025, India

ACS Omega, 2017, 2 (8), pp 5137–5141

DOI: 10.1021/acsomega.7b00819

http://pubs.acs.org/doi/abs/10.1021%2Facsomega.7b00819

*E-mail: ds.reddy@ncl.res.in. Phone: +91-20-2590 2445 (D.S.R.).

ACS AuthorChoice – This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

INTRODUCTION

Benzimidazol-2-ones 1 are an important class of heterocycles and a privileged scaffold in medicinal chemistry. They consist of cyclic urea fused with the aromatic backbone, which can potentially interact in a biological system by various noncovalent interactions such as hydrogen bonding and π stacking. Benzimidazolone derivatives exhibit a wide range of biological activities, and they are useful in treating various diseases including cancer, type II diabetes, central nervous system disorders, pain management, and infectious disease.1 Selected compounds embedded with a benzimidazol-2-one moiety along with their use are captured in Figure 1. It is worth mentioning that oxatomide drug with a benzimidazol-2-one core was approved for marketing a few years ago.2a Very recently, US Food and Drug Administration approved a new drug called flibanserin for the treatment of hypoactive sexual desire disorder (HSDD) in females, which contains benzimidazol-2- one motif.2b

CONCLUSIONS

We have developed a mild and new protocol for the synthesis of benzimidazol-2-ones from quinoxalinediones through decarbonylation. The present methodology can be an addition to the toolbox to prepare benzimidazolones, and it will be useful in medicinal chemistry, particularly, late-stage functionalization of natural products, drug scaffolds, or an intermediate containing quinoxaline-2,3-diones. As direct application of this method, we have successfully developed a new route for the synthesis of recently approved drug flibanserin and a urea analogue of antibiotic natural product hunanamycin A. Later application demonstrates the utility of the present method in late-stage functionalization

Synthesis of 1-(2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethyl)-1,3-dihydro-2Hbenzo[d]imidazol-2-one (Flibanserin)

Flibanserin hydrochloride as white solid.

1H NMR (400MHz ,DMSO-d6)  11.06 (s, 1 H), 10.93 (br. s., 1 H), 7.54 – 7.41 (t, J = 7.9 Hz, 1 H), 7.36 – 7.22 (m, 3 H), 7.15 (d, J = 7.6 Hz, 1 H), 7.09 – 7.01 (m, 3 H), 4.30 (t, J = 6.7 Hz, 2 H), 4.01 (d, J = 11.6 Hz, 2 H), 3.75 (d, J = 10.4 Hz, 2 H), 3.54 – 3.43 (d, J = 4.2 Hz 2 H), 3.31 – 3.10 (m, 4 H);

HRMS (ESI): m/z calculated for C20H22ON4F3[M+H]+ 391.1740 found 391.1743;

Scheme 4. Synthesis of Flibanserin through Ring Contraction

The same methodology was applied for the synthesis of flibanserin, also known as “female viagra”, which is the first approved medication for treating HSDD in women and is classified as a multifunctional serotonin agonist antagonist.(14, 15) Our synthesis of flibanserin commenced with 1-benzyl-1,4-dihydroquinoxaline-2,3-dione 36,(16) which was reacted with known chloride 37(17) under the basic condition in DMF to give the desired product 38 in good yield. Compound 38 was subjected for the decarbonylative cyclization under the optimized condition to afford the product 39 in 59% yield. Finally, the benzyl group was deprotected using trifluoromethanesulfonic acid in toluene under microwave irradiation,(8b, 18) which gave flibanserin in excellent yield (Scheme 4). The final product was isolated as HCl salt, and all of the spectral data are in agreement with the published data.(15c)

Image result for Rahul D. Shingare

Rahul D. Shingare completed his M.Sc (Chemistry) from Fergusson College, Pune in 2008. He worked as a research associate in Ranbaxy and Lupin New drug discovery center, Gurgaon and Pune respectively until 2012 and currently pursuing his doctoral research in NCL – Pune from 2012.

Current Research Interests: Antibacterial Natural Product Hunanamycin A: Total Synthesis, SAR and Related Chemistry.

e-mail: rd.shingare@ncl.res.in

Akshay Kulkarni completed his M.Sc. from Ferguson College, Pune University in the year 2015 and joined our group as a Project Assistant in the month of October, 2015.

Current research interest: Synthesis of silicon incorporated biologically active antimalerial compounds.

e-mail : as.kulkarni@ncl.res.in

Image result for Rahul D. Shingare

Dr.D. Srinivasa Reddy
Organic Chemistry Division
CSIR-National Chemical Laboratory

14.

Stahl, S. M. Mechanism of action of Flibanserin, A multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder CNS Spectrums 2015, 20, 1 DOI: 10.1017/s1092852914000832

[CrossRef], [PubMed], [CAS]
15.

See, previous synthesis of Flibanserin:

(a) Bietti, G.; Borsini, F.; Turconi, M.; Giraldo, E.; Bignotti, M. For treatment of central nervous system disorders. U.S. Patent 5,576,318, 1996.

(b) Mohan, R. D.; Reddy, P. K.;Reddy, B. V. Process for the preparation of Flibanserin involving novel intermediates. WO2010128516 A2,2010.

(c) Yang, F.; Wu, C.; Li, Z.; Tian, G.; Wu, J.; Zhu, F.; Zhang, J.; He, Y.; Shen, J. A Facile route of synthesis for making Flibanserin Org. Process Res. Dev. 2016, 20, 1576 DOI: 10.1021/acs.oprd.6b00108

[ACS Full Text ], [CAS]
16.

Jarrar, A. A.; Fataftah, Z. A. Photolysis of some quinoxaline-1,4-dioxides Tetrahedron 1977, 33, 2127 DOI: 10.1016/0040-4020(77)80326-8

[CrossRef], [CAS]
17.

Xueong, X. Preparation method of Flibanserin. CN104926734 A, 2015.
18.

Rombouts, F.; Franken, D.; Martínez-Lamenca, C.; Braeken, M.; Zavattaro, C.; Chen, J.; Trabanco, A. A.Microwave-assisted N-debenzylation of amides with triflic acid Tetrahedron Lett. 2010, 51, 4815 DOI: 10.1016/j.tetlet.2010.07.022

[CrossRef], [CAS]

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Ecocatalyzed Suzuki cross coupling of heteroaryl compounds

spectroscopy, SYNTHESIS Comments Off

Jul 302017

Ecocatalyzed Suzuki cross coupling of heteroaryl compounds

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01672G, Paper

Guillaume Clave, Franck Pelissier, Stephane Campidelli, Claude Grison
A bio-based EcoPd was developed for the Suzuki cross coupling of heteroaryl compounds.

Ecocatalyzed Suzuki cross coupling of heteroaryl compounds

Guillaume Clavé,^a Franck Pelissier,^a Stéphane Campidelli^b and Claude Grison*^a

*Corresponding authors

^aBio-inspired Chemistry and Ecological Innovations (ChimEco) UMR 5021 CNRS-University of Montpellier, Cap Delta, 1682 rue de la Valsière, 34790 Grabels, France
E-mail: claude.grison@cnrs.fr

^bLICSEN, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay 91191 Gif-sur-Yvette Cedex, France

Abstract

A bio-based EcoPd was developed for the Suzuki cross coupling of heteroaryl compounds. Based on the ability of Eichhornia crassipes to bioconcentrate Pd in its roots, we addressed the transformation of plant-derived Pd metals to green catalysts. The methodology is based on eco-friendly procedures. It allowed the preparation of a wide range of heterocyclic biaryl and heterocyclic–heterocyclic biaryl compounds, with a low Pd catalyst loading. EcoPd was found to have the ideal microstructure to promote complex Suzuki reactions without ligands or additives. For the first time, post-reaction solution was treated by rhizofiltration. The resulting EcoPd has been reused with the same performance. This work has established the ecocatalysis concept as a powerful strategy for Pd sustainability, with the development of homogeneous catalysts that are easily recycled and reused.

2-Bromothiophene (20 g, 125 mmol), Phenyl boronic acid (16.8 g, 138 mmol), potassium carbonate (20.7 g, 150 mmol) and EcoPd1 (113 mg, 125 µmol of Pd, 13.3 mg of Pd, EcoPd1 at 11.7 wt% of Pd) were suspended into degassed glycerol (200 mL). The mixture was stirred at 120°C for 4h thanks to an oil bath under an argon atmosphere. The reaction was checked for completion by TLC (cyclohexane) and GCMS analysis after a short extraction of the organic material: 10 µL of the crude were added into a 1 mL microtube containing a mixture of water and AcOEt (800 µL, 1:1, v/v) ; the microtube was vortexed before using the organic layer to perform analysis. Deionised water (500 mL) and AcOEt (500 mL) were added into the flask and the mixture filtered through fritted glass to isolate black Pd for recycling. The organic layer was further washed by deionised water (500 mL x 3) before drying over Na2SO4. The organic layer was filtered and concentrated under vacuum. The residue was then purified by chromatography on a silica gel column (250 g) with pure cyclohexane as the mobile phase, giving the desired coupled compound as a white powder (18 g, 112.5 mmol, yield 90%) Rf = 0.7 (cyclohexane).

1H NMR (300 MHz, CDCl3):  = 7.10- 7.13 (m, 2H), 7.44-7.26 (m, 5H), 7.38-7.33 (m, 1H).

13C NMR (75.5 MHz, CDCl3):  = 123.0, 124.8, 125.9, 127.4, 128.0, 128.8, 134.4, 144.4.

MS (EI): m/z = 160 (M+ , 100%), 128 (21%), 115 (54%), 89 (17%) calcd for C10H8S: 159.99.

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Catalytic carbonyl hydrosilylations via a titanocene borohydride-PMHS reagent system

spectroscopy, SYNTHESIS Comments Off

Jul 142017

Catalytic carbonyl hydrosilylations via a titanocene borohydride-PMHS reagent system

Catal. Sci. Technol., 2017, Advance Article

DOI: 10.1039/C7CY01088E, Paper

Godfred D. Fianu, Kyle C. Schipper, Robert A. Flowers II
Catalytic amounts of titanocene(III) borohydride, generated under mild conditions from commercially available titanocene dichloride, in concert with a stoichiometric hydride source is shown to effectively reduce aldehydes and ketones to their respective alcohols in aprotic media.

From the journal:

Catalytic carbonyl hydrosilylations viaa titanocene borohydride–PMHS reagent system

Godfred D. Fianu,^a Kyle C. Schipper^a and Robert A. Flowers II*^a

Author affiliations

*Corresponding authors

^aDepartment of Chemistry, Lehigh University, Bethlehem, USA
E-mail: rof2@lehigh.edu

Abstract

Reduction of a wide range of aldehydes and ketones with catalytic amounts of titanocene borohydride in concert with a stoichiometric poly(methylhydrosiloxane) (PMHS) reductant is reported. Preliminary mechanistic studies demonstrate that the reaction is mediated by a reactive titanocene(III) complex, whose oxidation state remains constant throughout the reaction.

Godfred Fianu

Lehigh University , Bethlehem · Department of Chemistry

Robert A Flowers

Danser Distinguished Faculty Chair in Chemistry and Deputy Provost for Faculty Affairs

Lehigh University , Bethlehem · Department of Chemistry

Lehigh University

Department of Chemistry

Bethlehem, United States

Phenyl methanol (2-c)
Phenyl methanol (2-c) was prepared from benzaldehyde (1-c) by the procedure outlined
in GP1. NMR analysis showed 100% conversion in 1 hour. 86% isolated yield of alcohol
product was obtained after complete workup.

1H NMR (400 MHz, CDCl3) δ 7.37 – 7.26 (m,5H), 4.59 (s, 2H), 2.99 (s, 1H).

13C NMR (101 MHz, CDCl3) δ 140.92, 128.56, 127.60, 127.07,77.52, 77.20, 76.88, 65.04.

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Control of stereoselectivity of benzylic hydroxylation catalysed by wild-type cytochrome P450BM3 using decoy molecules

SYNTHESIS, Uncategorized Comments Off

Jul 142017

Control of stereoselectivity of benzylic hydroxylation catalysed by wild-type cytochrome P450BM3 using decoy molecules

Catal. Sci. Technol., 2017, Advance Article
DOI: 10.1039/C7CY01130J, Paper

Kazuto Suzuki, Joshua Kyle Stanfield, Osami Shoji, Sota Yanagisawa, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshihito Watanabe
The benzylic hydroxylation of non-native substrates was catalysed by cytochrome P450BM3, wherein “decoy molecules” controlled the stereoselectivity of the reactions.

From the journal:

Control of stereoselectivity of benzylic hydroxylation catalysed by wild-type cytochrome P450BM3 using decoy molecules

Kazuto Suzuki,^a Joshua Kyle Stanfield,^a Osami Shoji,*^a^b Sota Yanagisawa,^a Hiroshi Sugimoto,^b^c Yoshitsugu Shiro^d and Yoshihito Watanabe*^e

Abstract

The hydroxylation of non-native substrates catalysed by wild-type P450BM3 is reported, wherein “decoy molecules”, i.e., native substrate mimics, controlled the stereoselectivity of hydroxylation reactions. We employed decoy molecules with diverse structures, resulting in either a significant improvement in enantioselectivity or clear inversion of stereoselectivity in the benzylic hydroxylation of alkylbenzenes and cycloalkylbenzenes. For example, supplementation of wild-type P450BM3 with 5-cyclohexylvaleric acid-L-phenylalanine (5CHVA-Phe) and Z-proline-L-phenylalanine yielded 53% (R) ee and 56% (S) ee for indane hydroxylation, respectively, although 16% (S) ee was still observed in the absence of any additives. Moreover, we performed a successful crystal structure analysis of 5CHVA-L-tryptophan-bound P450BM3 at 2.00 Å, which suggests that the changes in selectivity observed were caused by conformational changes in the enzyme induced by binding of the decoy molecules.

Kazuto Suzuki

suzuki.kazuto*c.mbox.nagoya-u.ac.jp

Yoshihito Watanabe

yoshi*nucc.cc.nagoya-u.ac.jp

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2,2,5,5-Tetramethyltetrahydrofuran (TMTHF): a non-polar, non-peroxide forming ether replacement for hazardous hydrocarbon solvents

SYNTHESIS Comments Off

Jul 132017

2,2,5,5-Tetramethyltetrahydrofuran (TMTHF): a non-polar, non-peroxide forming ether replacement for hazardous hydrocarbon solvents

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01392B, Paper

Fergal Byrne, Bart Forier, Greet Bossaert, Charly Hoebers, Thomas J. Farmer, James H. Clark, Andrew J. Hunt
An inherently non-peroxide forming ether solvent, 2,2,5,5-tetramethyltetrahydrofuran (2,2,5,5-tetramethyloxolane), has been synthesized from readily available and potentially renewable feedstocks, and its solvation properties have been tested

2,2,5,5-Tetramethyltetrahydrofuran (TMTHF): a non-polar, non-peroxide forming ether replacement for hazardous hydrocarbon solvents

Fergal Byrne,^a Bart Forier,^b Greet Bossaert,^b Charly Hoebers,^b Thomas J. Farmer,^a James H. Clark^a and Andrew J. Hunt*^a

*Corresponding authors

^aGreen Chemistry Centre of Excellence, University of York, York YO10 5DD, UK
E-mail: andrew.hunt@york.ac.uk

^bNitto Belgium, NV Eikelaarstraat 22, Belgium

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC01392B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Abstract

An inherently non-peroxide forming ether solvent, 2,2,5,5-tetramethyltetrahydrofuran (2,2,5,5-tetramethyloxolane), has been synthesized from readily available and potentially renewable feedstocks, and its solvation properties have been tested. Unlike traditional ethers, its absence of a proton at the alpha-position to the oxygen of the ether eliminates the potential to form hazardous peroxides. Additionally, this unusual structure leads to lower basicity compared with many traditional ethers, due to the concealment of the ethereal oxygen by four bulky methyl groups at the alpha-position. As such, this molecule exhibits similar solvent properties to common hydrocarbon solvents, particularly toluene. Its solvent properties have been proved by testing its performance in Fischer esterification, amidation and Grignard reactions. TMTHF’s differences from traditional ethers is further demonstrated by its ability to produce high molecular weight radical-initiated polymers for use as pressure-sensitive adhesives.