N-Methyl-3-Bromo-5-Methyl Pyrazole

N-Methyl-3-Bromo-5-Methyl Pyrazole

3·HCl as a white solid in 27% yield; sublimes at 40 °C; 1H NMR (500 MHz, DMSO-d6) δ 11.88 (s, 1 H), 6.07 (s, 1 H), 3.62 (s, 3 H), 2.16 (s, 3 H); 13C NMR (125 MHz, DMSO-d6) δ 141.7, 123.0, 107.5, 36.5, 10.9; HRMS-ESI (m/z) calcd for C5H8N2Br [M + H]+ 174.9864, found 174.9864.

3·TfOH as an off-white solid; mp = 145 °C; 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1 H), 6.06 (s, 1 H), 3.62 (s, 3 H), 2.16 (s, 3 H); 13C NMR (100 MHz, DMSO-d6) δ 141.9, 123.2, 121.2 (q, J = 320 Hz), 107.6, 36.5, 10.9; HRMS-ESI (m/z) calcd for C5H8N2Br [M + H]+ 174.9864, found 174.9865.

Development of Scalable Processes for the Preparation of N-Methyl-3-Bromo-5-Methyl Pyrazole

Richard J. Fox* , Chester E. Markwalter, Michael Lawler, Keming Zhu, Jacob Albrecht, Joseph Payack, and Martin D. Eastgate

Chemical & Synthetic Development, Bristol-Myers Squibb Company, P.O. Box 191 New Brunswick, New Jersey 08903-0191, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00091

 

*E-mail: richard.fox@bms.com.

The development and optimization of two scalable routes to N-methyl-3-bromo-5-methyl pyrazole is described. The initial Sandmeyer route entailed a three-step sequence from crotonitrile and methyl hydrazine, proceeding through the 3-amino pyrazole intermediate. Due to the GTI liability of the 3-amino pyrazole intermediate, a tedious steam-distillation, and <30% overall yield, we developed a second-generation Sandmeyer-free approach from methyl crotonate and methyl hydrazine which leveraged a condensation, bromination, and oxidation sequence. Process development led to the improved preparation of N-methyl-3-bromo-5-methyl pyrazole with increased efficiency and overall yield. The isolation, handling, and storage of the final product was greatly improved through the generation of the triflic acid salt, and salt form studies are also discussed.

   

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00091

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Asymmetric synthesis of ent-fragransin C1

http://pubs.rsc.org/en/Content/ArticleLanding/2017/OB/C7OB00749C?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FOB+%28RSC+-+Org.+Biomol.+Chem.+latest+articles%29#!divAbstract

Asymmetric synthesis of ent-fragransin C1

Org. Biomol. Chem., 2017, Advance Article
DOI: 10.1039/C7OB00749C, Paper

Santikorn Chaimanee, Manat Pohmakotr, Chutima Kuhakarn, Vichai Reutrakul, Darunee Soorukram
The first asymmetric synthesis of ent-fragransin C1 bearing 2,3-anti-3,4-syn-4,5-anti stereochemistries is reported.

Asymmetric synthesis of ent-fragransin C1

Santikorn Chaimanee,a  Manat Pohmakotr,a  Chutima Kuhakarn,a  Vichai Reutrakula  and  Darunee Soorukram*a 

*Corresponding authors

aDepartment of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand
E-mail: darunee.soo@mahidol.ac.th
Fax: +662 354 7151
Tel: +662201 5148

Abstract

The first asymmetric synthesis of ent-fragransin C1 was reported. The key step involves an intramolecular C–O bond formation (furan ring formation) via chemoselective generation of the benzylic carbocation leading to the 2,3-anti-3,4-syn-4,5-anti-tetrahydrofuran moiety as a single diastereomer in good yield. Our synthesis confirms that ent-fragransin C1 possesses 2R,3R,4S,5S configurations.

4-[(2R,3R,4S,5S)-5-(4-Hydroxy-3-methoxyphenyl)-3,4- dimethyltetrahydrofuran-2-yl]-2,6-dimethoxyphenol (ent-1). A flame-dried.......................... in vacuo, the crude product was purified by column chromatography (60% EtOAc in hexanes) to afford ent-1 as a sticky brownish oil (15.3 mg, 99% yield) as a single diastereomer (400 MHz 1 H NMR analysis). Rf 0.18 (40% EtOAc in hexanes);

[α]27 D -6.97 (c 0.60, CHCl3 ) (lit. [α]D +3.8 (c 0.60, CHCl3 ); 4a

UV (MeOH) λmax (log ε) 208 (0.85), 233 (0.24), 279 (0.07) nm; CD (MeOH) 226 (Δε 2.23), 250 (Δε +0.12).

1 H NMR (400 MHz, acetone-d6 ): δ 7.51 (s, 1H, OH), 7.12 (s, 1H, OH), 7.10 (d, J = 1.8 Hz, 1H, ArH), 6.92 (d, J = 8.1, 1.8 Hz, 1H, ArH), 6.82 (d, J = 8.1 Hz, 1H, ArH), 6.77 (s, 2H, 2  ArH), 4.43 (d, J = 5.4 Hz, 1H, 2  xCH), 3.86 (s, 3H, OCH3 ), 3.83 (s, 6H, 2  xOCH3 ), 2.202.45 (m, 2H, 2  xCH), 1.03 (d, J = 6.7 Hz, 3H, CH3 ), 1.00 (d, J = 6.7 Hz, 3H, CH3 ).

13C NMR (100 MHz, acetone-d6 ): δ 149.0 (2  C), 148.7 (C), 147.3 (C), 136.6 (C), 135.5 (C), 134.7 (C), 120.4 (CH), 115.9 (CH), 111.2 (CH), 105.1 (2  CH), 88.7 (CH), 88.4 (CH), 57.0 (2  CH3 ), 56.6 (CH3 ), 46.1 (CH), 45.7 (CH), 13.7 (CH3 ), 13.5 (CH3 ).

IR (CHCl3 ): νmax 3542s, 1616m, 1517s, 1465s, 1117s cm−1 .

MS (ISCID): m/z (%) relative intensity 397 [(M + Na)+ , 100], 357 (1).

HRMS (ESI-TOF) calcd for C21H26O6Na [M + Na]+ : 397.1627, found: 397.1622.

4 (a) M. Hattori, S. Hada, Y. Kawata, Y. Tezuka, T. Kikuchi and T. Namba, Chem. Pharm. Bull., 1987, 35, 3315; (

Darunee Soorukram

Assistant Professor

Darunee Soorukram

Education

• B.Sc. (Chemistry), Khon Kean University, Khon Kean, Thailand
• M.Sc. (Organic Chemistry), Mahidol University, Bangkok, Thailand
• Ph.D., Ludwig-Maximilians-University, Munich, Germany

Name : Darunee Soorukram     ดรุณี สู้รักรัมย์ Title : Assistant Professor Dr. Education : Ph.D. (Ludwig-Maximilians-University), Germany     Expertise : -     Contact Address : Department : Chemistry   Room : C418B   Phone : (662) 201 5148     E-Mail : darunee.soo@mahidol.ac.th         More Information : CV from Dept. Chemistry Website       รางวัลวิทยานิพนธ์ ระดับดีเยี่ยม (สาขาวิทยาศาสตร์เคมีและเภสัช) จากสภาวิจัยแห่งชาติ   Most Recent Articles from Scopus : Soorukram D (Author ID: 6506453550) O -Iodoxybenzoic Acid (IBX)-Iodine Mediated One-Pot Deacylative Sulfonylation of 1,3-Dicarbonyl Compounds: A Synthesis of β-Carbonyl Sulfones  2017; Synthesis (Germany); Katrun, P. | Songsichan, T. | Soorukram, D. | Pohmakotr, M. | Reutrakul, V. |... Cytotoxic lanostanes from fruits of Garcinia wallichii Choisy (Guttiferae)  2016; Bioorganic and Medicinal Chemistry Letters; Hongthong, S. | Meesin, J. | Pailee, P. | Soorukram, D. | Kongsaeree, P. |... Iodine-catalyzed Sulfonylation of Arylacetylenic Acids and Arylacetylenes with Sodium Sulfinates: Synthesis of Arylacetylenic Sulfones  (Cited 11 time(s)) 2016; Journal of Organic Chemistry; Meesin, J. | Katrun, P. | Pareseecharoen, C. | Pohmakotr, M. | Reutrakul, V. |... Decarboxylative sulfonylation of arylpropiolic acids with sulfinic acids: synthesis of (E)-vinyl sulfones  (Cited 1 time(s)) 2016; Tetrahedron; Meesin, J. | Katrun, P. | Reutrakul, V. | Pohmakotr, M. | Soorukram, D. |... Nitration-Oximization of Styrene Derivatives with tert-Butyl Nitrite: Synthesis of α-Nitrooximes  2016; Chinese Journal of Chemistry; Chumnanvej, N. | Katrun, P. | Pohmakotr, M. | Reutrakul, V. | Soorukram, D. |... Intramolecular Conjugate Ene Reaction of γ-Difluoromethyl- and γ-Trifluoromethyl-α,β-Unsaturated γ-Butyrolactones  2015; Journal of Organic Chemistry; Srimontree, W. | Masusai, C. | Soorukram, D. | Kuhakarn, C. | Reutrakul, V. |... Stereoselective Synthesis of 1-Fluoro-exo,exo-2,6-diaryl-3,7-dioxabicyclo[3.3.0]octanes: Synthesis of (±)-1-Fluoromembrine  (Cited 1 time(s)) 2015; Journal of Organic Chemistry; Punirun, T. | Soorukram, D. | Kuhakarn, C. | Reutrakul, V. | Pohmakotr, M. Synthesis of γ-difluoromethyl α,β-unsaturated γ-butyrolactones using PhSCF<inf>2</inf>SiMe<inf>3</inf> as a difluoromethylating agent  (Cited 3 time(s)) 2015; European Journal of Organic Chemistry; Issaree, A. | Masusai, C. | Soorukram, D. | Kuhakarn, C. | Reutrakul, V. |... Silver-mediated decarboxylative fluorination of paraconic acids: A direct entry to β-fluorinated γ-butyrolactones  (Cited 10 time(s)) 2015; European Journal of Organic Chemistry; Phae-Nok, S. | Soorukram, D. | Kuhakarn, C. | Reutrakul, V. | Pohmakotr, M. PhI(OAc)<inf>2</inf> mediated decarboxylative sulfonylation of β-aryl-α,β-unsaturated carboxylic acids: A synthesis of (E)-vinyl sulfones  (Cited 18 time(s)) 2015; Organic and Biomolecular Chemistry; Katrun, P. | Hlekhlai, S. | Meesin, J. | Pohmakotr, M. | Reutrakul, V. |... Access all results for your search in Scopus

Contact

Phone: +66.(0).2.201.5148

LAB Tel: +66.(0).2.201.5149
Fax: +66.(0).2.354.7151
E-mail:darunee.soo@mahidol.ac.th

Address:
Room C418B
Department of Chemistry,
Faculty of Science, Mahidol University,
Rama 6 Road, Ratchthewee
Bangkok 10400 Thailand

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Dr. Vinayak Pagar( GUEST BLOGGER) Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds

Discussing my paper........

Metal-catalyzed cycloadditions of alkenyldiazo reagents are useful tools to access carbo- and heterocycles.[1] These diazo compounds are chemically sensitive toward both Brønsted orLewis acids. Their reported cycloadditions rely heavily on the formation of metal carbenes to initiate regio- and stereoselective [3+n] cycloadditions (n=2–4) with suitable dipolarophiles.[2–4] A noncarbene route was postulated for a few copper-catalyzed cycloadditions of these diazo species, but they resulted in complete diazo decomposition.[3a, 4a, 5] oyle and co-workers reported[4a] a [3+2] cycloaddition of the alkenylrhodium carbene A with imines to give dihydropyrroles (Scheme 1a). We proposed a cycloaddition the tetrahydroquinoline derivatives 3 and 3’, as well as the tetrahydro-1H-benzo[b]azepine species 4. Access to these frameworks are valuable

Access to these frameworks are valuable for the preparation of several bioactive molecules including 2-phenyl-2,3-
dihydroquinolone,[8a] L-689,560,[8b] torcetrapib,[8c] martinellic acid,[8d] OPC-31260,[8e] OPC-51803,[8f] and tetraperalone A (Figure 1).[8g] Their specific biological functions have been well documented.[8]

Spectral data for ethyl 2-diazo-2-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl) acetate (2a)

Yellow Semi-Solid;

IR (KBr, cm-1 ): 3542 (m), 2117 (s), 3015 (s), 1737 (s), 1564 (s), 1334 (m), 1137 (s), 817 (s);

1H NMR (600 MHz, CDCl3): δ 7.41 (d, J = 7.3 Hz, 2 H), 7.36 ~ 7.33 (m, 2 H), 7.30 (t, J = 7.3 Hz, 2 H), 7.07 (d, J = 7.6 Hz, 1 H), 7.04 (t, J = 7.6 Hz, 1H), 6.71 (t, J = 7.2 Hz, 1H), 6.55 (d, J = 7.9 Hz, 1H) 4.56 (dd, J = 11.0, 2.3 Hz, 1H ), 4.25 (q, J = 7.1 Hz, 2H ), 4.21 (dd, J = 11.0, 5.3 Hz, 1H ), 4.01 (s, 1H) 2.36 ~ 2.33 (m, 1H), 2.00 (dd, J = 11.8, 2.3 Hz, 1H ), 1.28 (t, J = 7.1 Hz, 3H);

13C NMR (150 MHz, CDCl3): δ 167.2, 145.3, 142.9, 128.6, 128.0, 127.8, 126.5, 126.4, 118.8, 117.9, 114.4, 60.9, 59.5, 56.2, 36.8, 32.6, 14.4.

HRMS calcd for C19H19N3O2: 321.1477; found: 321.1483.

Volume 51, Issue 47
November 19, 2012
Pages 11809–11813

Communication
Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds^†
Authors, Appaso Mahadev Jadhav, Vinayak Vishnu Pagar, and Rai-Shung Liu*, DOI: 10.1002/anie.201205692

 ^†We thank the National Science Council, Taiwan, for financial support of this work., [*] A. M. Jadhav, V. V. Pagar, Prof. Dr. R.-S. Liu

Department of Chemistry, National Tsing Hua University
Hsinchu (30013) (Taiwan)
E-mail: rsliu@mx.nthu.edu.tw

Abstract

Rings aplenty: A HOTf-catalyzed (Tf=trifluoromethanesulfonyl) Povarov reaction of alkenyldiazo species has been developed and delivers diazo-containing cycloadducts stereoselectively (see scheme). The resulting cycloadducts provide access to six- and seven-membered azacycles through the generation of metal carbenes as well as the functionalization of diazo group.
[1] Selected reviews: a) M. P. Doyle,M. A. McKervy, T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds,  Wiley, New York, 1998; b) A. Padwa, M. D. Weingarten, Chem. Rev. 1996, 96, 223; c) H. M. L. Davies, J. R. Denton, Chem. Soc. Rev. 2009, 38, 3061; d) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010, 110, 704; e) H. M. L. Davies, D. Morton, Chem. Soc. Rev. 2011, 40, 1857; f) Z. Zhang, J. Wang, Tetrahedron
2008, 64, 6577.
[2] Selected examples for carbocyclic cycloadducts, see: a) L. Deng, A. J. Giessert, O. O. Gerlitz, X. Dai, S. T. Diver, H. M. L. Davies, J. Am. Chem. Soc. 2005, 127, 1342; b) H. M. L. Davies, Adv. Cycloaddit. 1999, 5, 119; c) H. M. L. Davies, B. Xing, N. Kong, D. G. Stafford, J. Am. Chem. Soc. 2001, 123, 7461; d) H. M. L. Davies, T. J. Clark, H. D. Smith, J. Org. Chem. 1991, 56, 3819; e) Y. Liu, K. Bakshi, P. Zavalij, M. P. Doyle, Org. Lett. 2010, 12, 4304; f) J. P. Olson, H. M. L. Davies, Org. Lett. 2008, 10, 573.
[3] For oxacyclic cycloadducts, see: a) X. Xu, W.-H. Hu, P. Y. Zavalij, M. P. Doyle, Angew. Chem. 2011, 123, 11348; Angew. Chem. Int. Ed. 2011, 50, 11152; b) M. P. Doyle, W. Hu, D. J. Timmons, Org. Lett. 2001, 3, 3741.
[4] For azacyclic cycloadducts, see selected reviews: a) M. P. Doyle, M. Yan, W. Hu, L. Gronenberg, J. Am. Chem. Soc. 2003, 125, 4692; b) J. Barluenga, G. Lonzi, L. Riesgo, L. A. L pez, M. Tomas, J. Am. Chem. Soc. 2010, 132, 13200; c) M. Yan, N. Jacobsen, W. Hu, L. S. Gronenberg, M. P. Doyle, J. T. Colyer, D. Bykowski, Angew. Chem. 2004, 116, 6881; Angew. Chem. Int. Ed. 2004, 43, 6713; d) X.Wang, X. Xu, P. Zavalij, M. P. Doyle, J. Am.
Chem. Soc. 2011, 133, 16402; e) Y. Lian, H. M. L. Davies, J. Am. Chem. Soc. 2010, 132, 440; f) X. Xu, M. O. Ratnikov, P. Y. Zavalij, M. P. Doyle, Org. Lett. 2011, 13, 6122; g) V. V. Pagar, A. M. Jadhav, R.-S. Liu, J. Am. Chem. Soc. 2011, 133, 20728; h) R. P. Reddy, H. M. L. Davies, J. Am. Chem. Soc. 2007, 129, 10312.
[5] Y. Qian, X. Xu, X.Wang, P. Zavalij,W. Hu, M. P. Doyle, Angew. Chem. 2012, 124, 6002; Angew. Chem. Int. Ed. 2012, 51, 5900.
[6] Povarov reactions refer to the formal [4+2] cycloadditions of Naryl imines with enol ethers or enamines. See reviews: a) L. S. Povarov, Russ. Chem. Rev. 1967, 36, 656; b) V. V. Kouznetsov, Tetrahedron 2009, 65, 2721; c) D. Bello, R. Ram n, R. Lavilla, Curr. Org. Chem. 2010, 14, 332; d) M. A. McCarrick, Y. D. Wu, K. N. Houk, J. Org. Chem. 1993, 58, 3330; e) A. Whiting, C. M. Windsor, Tetrahedron 1998, 54, 6035.
[7] For Povarov reactions catalyzed by Brønsted acids, see selected examples: a) H. Xu, S. J. Zuend, M. G. Woll, Y. Tao, E. N. Jacobson, Science 2010, 327, 986; b) T. Akiyama, H. Morita, K. Fuchibe, J. Am. Chem. Soc. 2006, 128, 13070; c) H. Liu, G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am. Chem. Soc. 2009, 131, 4598; d) G. Dagousset, J. Zhu, G. Masson, J. Am. Chem. Soc. 2011, 133, 14804; e) H. Ishitani, S. Kobayashi, Tetrahedron Lett. 1996, 37, 7357; f) G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi, A. Ricci, Chem. Commun.
2010, 46, 327; g) L. He, M. Bekkaye, P. Retailleau, G. Masson, Org. Lett. 2012, 14, 3158.
[8] a) Y. Xia, Z.-Y. Yang, P. Xia, K. F. Bastow, Y. Tachibana, S.-C. Kuo, E. Hamel, T. Hackl, K.-H. Lee, J. Med. Chem. 1998, 41, 1155; b) R.W. Carling, P. D. Leeson, A. M. Moseley, J. D. Smith, K. Saywell, M. D. Trickelbank, J. A. Kemp, G. R. Marshall, A. C. Foster, S. Grimwood, Bioorg. Med. Chem. Lett. 1993, 3, 65;
c) D. B. Damon, R. W. Dugger, R.W. Scott, U.S. Patent 6,689,897, 2004; d) D. A. Powell, R. A. Batey, Org. Lett. 2002, 4, 2913; e) A. Matsuhisa, K. Kikuchi, K. Sakamoto, T. Yatsu, A. Tanaka, Chem. Pharm. Bull. 1999, 47, 329; f) M. Y. Christopher, E. A. Christine, D. M. Ashworth, J. Barnett, A. J. Baxter, J. D. Broadbridge, R. J. Franklin, S. L. Hampton, P. Hudson, J. A. Horton, P. D. Jenkins, A. M. Penson, G. R.W. Pitt, P. Rivi re,
P. A. Robson, D. P. Rooker, G. Semple, A. Sheppard, R. M.Haigh, M. B. Roe, J. Med. Chem. 2008, 51, 8124; g) C. Li, X. Li, R. Hong, Org. Lett. 2009, 11, 4036.

About author( Me)

Dr. Vinayak Pagar

Postdoctoral Research Fellow at The Ohio State University

Vinayak Vishnu Pagar was born in Nasik, Maharashtra (India) in 1983. He obtained his BSc and MSc degrees in chemistry from the University of Pune (India) in 2004 and 2006, respectively. From 2006–2010, he worked as Research Associate in pharmaceutical companies like Jubilant Chemsys Ltd. and Ranbaxy Laboratories Ltd. (India). In 2010, he joined the group of Professor Rai-Shung Liu to pursue his PhD degree in National Tsing Hua University (Taiwan) and completed it in 2014. Subsequently, he worked as a postdoctoral fellow in the same group for one year. Currently, he is working as a Research Scientist at The Ohio State University, Columbus, Ohio USA. His research focused on the development of new organic reactions by using transition-metal catalysis such Gold, Silver, Rhodium, Zinc, Cobalt, Nickel and Copper metals which enables mild, diastereoselective, enantioselective and efficient transformations of variety of readily available substrates to wide range of synthetically useful nitrogen and oxygen containing heterocyclic products which are medicinally important. He published his research in a very high impact factor international Journals includes  J. Am. Chem. Soc.,  Angew. Chem. Int. Ed.,  J. Org. Chem.,  Chem- A. Eur. Journal,  Org. Biomol. Chem., and Synform (Literature Coverage).

Dr. Vinayak Pagar

Postdoctoral Researcher

Department of Chemistry and Biochemistry

The Ohio State University

100 West 18th Avenue

Columbus, Ohio 43210 USA

vinayak.pagar@gmail.com

/////////Vinayak Pagar, Postdoctoral Research Fellow, The Ohio State University, blog, Povarov Reaction, Carbene Generation Sequence,  Alkenyldiazocarbonyl Compounds

NOESY NMR EXAMPLE.....(3S,5S)-10-(4-Nitrophenyl)-4,5a,6,7,8,10-hexahydro-5H-pyrrolo-[1,2-a]thieno[3,2-e][1,4]diazepin-2-one (18β)

NOESY experiment of diastereomer 18β (3S, 5S)
(3S,5S)-10-(4-Nitrophenyl)-4,5a,6,7,8,10-hexahydro-5H-pyrrolo-[1,2-a]thieno[3,2-e][1,4]diazepin-2-one (18β)

(3S,5S)-10-(4-Nitrophenyl)-4,5a,6,7,8,10-hexahydro-5H-pyrrolo-[1,2-a]thieno[3,2-e][1,4]diazepin-2-one (18β): Pale orange wax, 62%(104.0 mg).
[α]D29 = +8.8 (c = 1.0, MeOH).

1H NMR (CDCl3,300 MHz): δ = 1.83–1.92 (m, 2 H), 2.14–2.21 (m, 2 H), 2.90 (td, J= 8.7 Hz, 1 H), 3.41–3.47 (m, 1 H), 3.91 (t, J = 6.6 Hz, 1 H), 5.66(s, 1 H), 7.17–7.24 (m, 3 H), 7.44 (d, J = 8.7 Hz, 2 H), 8.18 (t, J =8.7 Hz, 2 H) ppm.

13C NMR (CDCl3, 75 MHz): δ = 24.88, 27.44,56.40, 63.70, 82.66, 111.10, 120.28, 124.26 (2 C), 125.37, 127.05 (2C), 135.23, 146.30, 147.97, 173.56 ppm.

LC–MS (ESI+): m/z =330.1 [M + H]+. HRMS: calcd. for C16H16N3O3S 330.0912 [M +
H]+; found 330.0914.

DOI: 10.1002/ejoc.201500943
Eur. J. Org. Chem. 2015, 7146–7153


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trans-2-(benzo[d][1,3]dioxol-5-yl)-2-methylcyclopropane-1-carbonitrile

trans-2-(benzo[d][1,3]dioxol-5-yl)-2-methylcyclopropane-1-carbonitrile

yellowish solid (53 mg, 66%);

m.p. = 72 °C;

 1 H-NMR (600 MHz, CDCl3): δ = 6.77 – 6.71 (m, 3H), 5.94 (s, 2H), 1.63 – 1.59 (m, 4H), 1.50 (dd, J = 9.1, 5.0 Hz, 1H), 1.26 (t, J = 5.3 Hz, 1H);

13CNMR (151 MHz, CDCl3): δ = 147.80, 146.73, 136.69, 120.64, 120.23, 108.28, 108.17, 101.19, 28.75, 23.86, 21.40, 11.30;

 HRMS (ESI): m/z calc. for [C12H11O2NK]: 240.0414, found 240.04204;

 IR (KBr): νmax/cm-1 = 2972, 2897, 2231, 1490, 1457, 1434, 1349, 1226, 1080, 1033, 924, 869, 808, 728.

1H NMR PREDICT

13C NMR PREDICT

 Green Chem., 2017, Advance Article

DOI: 10.1039/C7GC00602K, Communication

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C[C@@]1([C@H](C#N)C1)C2=CC(OCO3)=C3C=C2

trans-2-phenylcyclopropane-1-carbonitrile

Towards nitrile-substituted cyclopropanes - a slow-release protocol for safe and scalable applications of diazo acetonitrile

 Green Chem., 2017, Advance Article

DOI: 10.1039/C7GC00602K, Communication

Katharina J. Hock, Robin Spitzner, Rene M. Koenigs
Applications of diazo acetonitrile in cyclopropa(e)nation reactions are realized in a slow-release protocol with bench-stable reagents. Cyclopropyl nitriles are obtained in one step in good diastereoselectivity on a gram-scale providing an efficient entry into this class of fragrances and drug-like molecules.

trans-2-phenylcyclopropane-1-carbonitrile

colorless solid (46 mg, 81%);

m.p. = 29°C;

1 H-NMR (600 MHz, CDCl3): δ = 7.34 – 7.30 (m, 2H), 7.28 – 7.24 (m, 1H), 7.12 – 7.08 (m, 2H), 2.63 (ddd, J = 9.2, 6.7, 4.7 Hz, 1H), 1.62 (dt, J = 9.2, 5.4 Hz, 1H), 1.55 (ddd, J = 8.7, 5.5, 4.8 Hz, 1H), 1.45 (ddd, J = 8.8, 6.7, 5.3 Hz, 1H);

13C-NMR (151 MHz, CDCl3): δ = 137.55, 128.76, 127.41, 126.31, 121.05, 24.90, 15.24, 6.63;

HRMS (ESI): m/z calc. for [C10H9NNa]: 166.06272, found 166.06276;

IR (KBr): νmax/cm-1 = 3044, 2235, 2098, 1761, 1600, 1461, 1220, 1051, 920, 705.

 The analytical data is in correspondence with the literature [2]

 

[2] M. Gao, N. N. Patwardhan, P. R. Carlier, J. Am. Chem. Soc., 2013, 135 (38), 14390–14400

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC00602K?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

Katharina J. Hock,^a  Robin Spitzner^a  and  Rene M. Koenigs*^a 

Author affiliations

*Corresponding authors

^aRWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, D-52074 Aachen, Germany
E-mail: rene.koenigs@rwth-aachen.de

Abstract

Diazo acetonitrile has long been neglected despite its high value in organic synthesis due to a high risk of explosions. Herein, we report our efforts towards the transient and safe generation of this diazo compound, its applications in iron catalyzed cyclopropanation and cyclopropenation reactions and the gram-scale synthesis of cyclopropyl nitriles.

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N-aminosulfonamides

 

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00083

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