Isosorbide dimethyl ether

CAS Registry No.:	5306-85-4
Molecular Formula:	C8H14O4	Molecular Weight:	174.2

 

13 C NMR

22.53 MHz
C8 H14 O4	0.05 ml : 0.5 ml CDCl3

 

1H NMR

 

IR NEAT

RAMAN

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Total synthesis of (-)-aritasone via the ultra-high pressure hetero-Diels-Alder dimerisation of (-)-pinocarvone

Total synthesis of (-)-aritasone via the ultra-high pressure hetero-Diels-Alder dimerisation of (-)-pinocarvone

Org. Biomol. Chem., 2017, Advance Article

DOI: 10.1039/C7OB02204B, Paper

Maliha Uroos, Phillip Pitt, Laurence M. Harwood, William Lewis, Alexander J. Blake, Christopher J. Hayes
The total synthesis of aritasone via the proposed biosyntheic hetero-Diels-Alder [4 + 2] cyclodimerisation of pinocarvove, has been achieved under ultra-high pressure (19.9 kbar) conditions

Total synthesis of (−)-aritasone via the ultra-high pressure hetero-Diels–Alder dimerisation of (−)-pinocarvone

Maliha Uroos,a  Phillip Pitt,b  Laurence M. Harwood,b  William Lewis,a  Alexander J. Blakea  and Christopher J. Hayes*a 

 Author affiliations

*Corresponding authors

aSchool of Chemistry, University of Nottingham, University Park, Nottingham, UK
E-mail:chris.hayes@nottingham.ac.uk
Fax: +44 (0)115951 3564
Tel: +44 (0)115 951 3045

bChemical Sciences Division, University of Reading, Whiteknights, Reading, UK

Christopher Hayes

Abstract

This paper describes a total synthesis of the terpene-derived natural product aritasone via the hetero-Diels–Alder [4 + 2] cyclodimerisation of pinocarvove, which represents the proposed biosyntheic route. The hetero-Diels–Alder dimerisation of pinocarvone did not proceed under standard conditions, and ultra-high pressure (19.9 kbar) was required. As it seems unlikely that these ultra-high pressures are accessible within a plant cell, we suggest that the original biosynthetic hypothesis be reconsidered, and alternatives are discussed.

 

Aritasone (1) A solution of pinocarvone (()-2) (100 mg, 0.66 mmol) in dichloromethane (5 mL) was pressurized to 19.9 kbar for 120 h. The 1H NMR spectrum of the crude reaction mixture showed significant change in the composition as compared to the starting material. The solvent was evaporated and the residue was purified by column chromatography (pentane/Et2O; 25/1) to afford aritasone (1) (20 mg, 40%) as a white solid; mp 101- 103 C; (lit3 mp 105-106 °C); []D 26 26.1 (c 0.40 in CHCl3); (lit3 []D 9 118); max/cm-1 (CHCl3) 2926, 2359, 1722, 1689, 1601, 1467, 1372, 1305, 1152; H (400 MHz; CDCl3, 298 K) 2.67 (2H, app dd, J 4.8, 2.5, H-2a, H-2b), 2.45-2.32 (3H, m, H-7a, H-15a, H-3), 2.15-2.01 (4H, m, H-10, H-12, H-15b, H-16a), 1.91-1.80 (2H, m, H-4, H-16b), 1.66 (1H, ddd, J 13.8, 6.4, 3.4, H-7b), 1.38 (3H, s, CH3), 1.29-1.22 (7H, br s, CH3, H-13a, H-13b, H-8a, H- 8b), 0.90 (3H, s, CH3), 0.80 (3H, s, CH3); C (100 MHz; CDCl3, 298 K) 209.5 (C), 142.9 (C), 112.8 (C), 80.8 (C), 45.2 (CH), 44.3 (CH), 43.7 (CH2), 40.9 (CH), 40.5 (C), 39.4 (CH), 38.3 (C), 33.2 (CH2), 32.7 (CH2), 27.7 (CH3), 27.3 (CH2), 27.3 (CH3), 26.3 (CH3), 22.5 (CH2), 22.1 (CH2), 20.9 (CH3); HRMS m/z (ES+ ) found 301.2162 (M + H) C20H29O2 requires 301.2162 and 323.1981 (M + Na) C20H28O2Na requires 323.1982. These data were consistent to those previously reported, 5, 7 however the value of the specific rotation5 differs significantly from that measured during the original isolation work.3

Christopher Hayes

Contact

• Room C16 School of Chemistry
  University Park
  Nottingham
  NG7 2RD
  UK
• 0115 951 3045
• 0115 951 3564
• chris.hayes@nottingham.ac.uk
• http://www.nottingham.ac.uk/~pczcjh/Homepage.html

Biography

Prof. Christopher Hayes began his academic career here in Nottingham with his B.Sc. in July 1992. Remaining at Nottingham, he completed his Ph.D. studies in organic chemistry, under the supervision of Professor Gerald Pattenden, in September 1995. In January 1996, on a NATO Postdoctoral Fellowship, he moved to the University of California at Berkeley where he worked in the group of Professor Clayton H. Heathcock. In September 1997, he returned to Nottingham as a Lecturer in Organic Chemistry, and has subsequently been promoted to Reader (2003), Associate Professor (2006) and Professor of Organic Chemistry (2011).

Research Summary

Research is centred in main-stream synthetic organic chemistry, focusing on the organic chemistry of biologically active molecules. His current research interests span a number of areas such as (i)… read more

Recent Publications

• NICOLLE, SIMON M., LEWIS, WILLIAM, HAYES, CHRISTOPHER J. and MOODY, CHRISTOPHER J., 2016. Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N-H Insertion Reaction of Metallocarbenes with -Aminoketone Derivatives: Angewandte Chemie-International Edition Angewandte Chemie-International Edition. 55(11), 3749-3753
• BARTON, NAOMI A., MARSH, BENJAMIN J., LEWIS, WILLIAM, NARRAIDOO, NATHALIE, SEYMOUR, GRAHAM B., FRAY, RUPERT and HAYES, CHRISTOPHER J., 2016. Accessing low-oxidation state taxanes: is taxadiene-4(5)-epoxide on the taxol biosynthetic pathway?: Chemical Science Chemical Science. 7(5), 3102-3107
• PALFRAMAN, MATTHEW J., ALHARTHY, RIMA D., POWALOWSKA, PAULINA K. and HAYES, CHRISTOPHER J., 2016. Synthesis of triazole-linked morpholino oligonucleotides via Cu-I catalysed cycloaddition: Organic & Biomolecular Chemistry Organic & Biomolecular Chemistry. 14(11), 3112-3119
• NICOLLE, SIMON M., HAYES, CHRISTOPHER J. and MOODY, CHRISTOPHER J., 2015. Alkyl Halide-Free Heteroatom Alkylation and Epoxidation Facilitated by a Recyclable Polymer-Supported Oxidant for the In-Flow Preparation of Diazo Compounds: Chemistry-a European Journal Chemistry-a European Journal. 21(12), 4576-4579

• View all publications

//////////////(-)-aritasone

 

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

 

1,2-Bis(3-methoxyphenyl)benzene

1,2-Bis(3-methoxyphenyl)benzene (5)

  

 1H NMR (500 MHz, DMSO-d6): δ 3.59 (s, 6H), 6.65 (dd, J = 2.5, 1.5 Hz, 2H), 6.70 (ddd, J = 7.5, 1.5, 1.0 Hz, 2H), 6.78 (ddd, J= 8.0, 2.5, 1.0 Hz, 2H), 7.16 (t, J = 8.0 Hz, 2H), 7.40–7.46 (m, 4H).

13C NMR (126 MHz, DMSO-d6): δ 54.8, 112.4, 115.0, 121.7, 127.7, 129.0, 130.2, 139.8, 142.4, 158.7.

HRMS (TOF MS EI+) for C20H18O2 [M]+: calcd 290.1307, found 290.1303.

Efficient and Practical Synthesis of Electron Transport Material and Its Key Intermediate

Xiangdong Zhao†, Guijie Li*† , Zhi-Qiang Zhu‡, Kun Fang†, Yuning Yang†, Jian Li‡ , and Yuanbin She*†

† State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, College of Chemical Engineering, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, Zhejiang 310014, P. R. China

‡ Department of Materials Science and Engineering, Arizona State University, Tempe, Arizona 85284, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00280

*E-mail: guijieli@zjut.edu.cn., *E-mail: sheyb@zjut.edu.cn.

Abstract

An efficient and practical synthesis of 2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)triphenylene 4 from two cheap commodity chemicals in five steps with a total yield of 48.6% was developed. This process had been successfully applied in the synthesis of electron transport material (ETM) BPyTP-2 in the gram scale with a total yield of 47.2%. This practical development of the key intermediate 4 opens a door in its further application in the synthesis of other triphenylene-based ETMs and host materials in the materials field.

/////////////http://pubs.acs.org/doi/10.1021/acs.oprd.7b00280

http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.7b00280/suppl_file/op7b00280_si_001.pdf

2H-1,3-Benzoxazine natural products and related bioactive molecules.

4-(2-Bromo-5-chlorobenzyl)-7-chloro-2-phenyl-2H-benzo[e][1,3]oxazine 2 as a light-yellow solid (82% yield).

1H NMR (500 MHz, CDCl3): δ (ppm) 7.55–7.52 (m, 3H), 7.42–7.34 (m, 3H), 7.30 (d, 1H, J = 3.5 Hz,) 7.29 (s, 1H), 7.12 (dd, 1H, J = 8.5 Hz, 2.5 Hz), 6.95–6.91 (m, 2H), 6.57 (1H, s), 4.16 (ABq, 2H, ΔδAB = 0.05, JAB = 16.5 Hz).

13C NMR (125 MHz, CDCl3): δ (ppm) 161.5, 155.8, 139.2, 138.9, 138.1, 133.8, 133.5, 130.6, 128.8, 128.7, 128.5, 127.0, 126.3, 122.6, 121.9, 117.3, 116.2, 88.9, 40.8.

HRMS TOF MS (m/z): [M + H]+ calcd for [C21H14BrCl2NO H] 445.9709; found 445.9713.

FTIR(neat): 3060, 1633, 1596, 1454, 1364, 1344 cm–1.

Spectroscopic data for 2 were identical to those reported in the literature.(4)

Li, H.; Belyk, K. M.; Yin, J.; Chen, Q.; Hyde, A.; Ji, Y.; Oliver, S.; Tudge, M.; Campeau, L.-C.; Campos, K. R. J. Am. Chem. Soc. 2015, 137,13728– 13731 DOI: 10.1021/jacs.5b05934

Development of a General Protocol To Prepare 2H-1,3-Benzoxazine Derivatives

Ji Qi*†∥ , Steven F. Oliver‡∥, Wensong Xiao§, Licheng Song§, and Karel M. J. Brands∥

† Department of Process Research and Development, MSD R&D (China) Co., Ltd., Building 21 Rongda Road, Wangjing R&D Base, Zhongguancun Electronic Zone West Zone, Beijing 100012, China

‡ Department of Process Research and Development, Merck Sharp & Dohme, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, United Kingdom

§ Department of Synthetic Chemistry, Pharmaron Beijing Co., Ltd., 6 Taihe Road BDA, Beijing, 100176, China

∥ Department of Process Research and Development, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00209

Publication Date (Web): August 23, 2017

Copyright © 2017 American Chemical Society

*E-mail: ji_qi@merck.com.

ACS Editors’ Choice – 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.

Abstract

A practical synthesis and detailed development process of 2H-1,3-benzoxazine derivatives catalyzed by aldimine and trifluoromethanesulfonic acid is described. A broad range of substrates with diverse steric and electronic properties were explored. Aliphatic/aromatic/heteroaromatic substrates all proceed well under conditions which have been optimized into a robust, scalable process.

http://pubs.acs.org/doi/full/10.1021/acs.oprd.7b00209

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Photochemical intramolecular amination for the synthesis of heterocycles

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02261A, Communication

Shawn Parisien-Collette, Corentin Cruche, Xavier Abel-Snape, Shawn K. Collins
Polycyclic heterocycles can be formed in good to excellent yields via photochemical conversion of the corresponding substituted aryl azides under irradiation with purple LEDs in a continuous flow reactor.

Photochemical intramolecular amination for the synthesis of heterocycles

 

Shawn Parisien-Collette,^a  Corentin Cruché,^a  Xavier Abel-Snape^a  and  Shawn K. Collins*^a 

 Author affiliations

*Corresponding authors

^aShawn Parisien-Collette, Corentin Cruché, Xavier Abel-Snape and Prof, Dr Shawn K. Collins, Department of Chemistry and Centre in Green Chemistry and Catalysis, Université de Montréal, CP 6128 Station Downtown, Montréal, Canada H3C 3J7
E-mail: shawn.collins@umontreal.ca

Abstract

Polycyclic heterocycles can be formed in good to excellent yields via photochemical conversion of the corresponding substituted aryl azides under irradiation with purple LEDs in a continuous flow reactor. The experimental set-up is tolerant to UV-sensitive functional groups while affording diverse carbazoles, as well as an indole and pyrrole framework, in short reaction times. The photochemical method is presumed to progress through a mechanism differing from the other methods of azide activation involving transition metal catalysis.

Methyl 9H-carbazole-2-carboxylate (9): Following the Photodecomposition Procedure A, starting from Methyl 2’-azido-[1,1’-biphenyl]-4-carboxylate, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a white solid (24.3 mg, 72 % yield). Following the Photodecomposition Procedure B, starting from Methyl 2’-azido-[1,1’- biphenyl]-4-carboxylate, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a white solid (27.7 mg, 82 % yield). NMR data was in accordance with what was previously reported.16
16 Takamatsu, K.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2014, 16, 2892-2895

NEXT..............

 

4-Isopropyl-9H-carbazole (14): Following the Photodecomposition Procedure A, starting from 2-azido-2’-isopropyl-1,1’-biphenyl, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a yellow solid (16.6 mg, 53 % yield). Following the Photodecomposition Procedure B, starting from 2-azido-2’-isopropyl-1,1’-biphenyl and using ethyl acetate as the solvant, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a yellow solid (16.0 mg, 51 % yield).

1H NMR (400 MHz, DMSO-d6) δ = 11.29 (s, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.39-7.31 (m, 3H), 7.19- 7.15 (m, 1H), 7.08-7.03 (m, 1H), 3.92-3.82 (m, 1H), 1.41 (d, J = 6.8 Hz, 6H);

13C NMR (100 MHz, DMSO-d6) δ = 143.9, 140.3, 140.1, 126.0, 125.2, 122.8, 122.2, 119.9, 119.1, 114.9, 111.2, 108.9, 30.2, 22.8 (2C);

HRMS (ESI) m/z calculated for C15H15N [M-H]- 208.1130; found 208.1126.

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