Fe/ppm Cu nanoparticles as a recyclable catalyst for click reactions in water at room temperature

Fe/ppm Cu nanoparticles as a recyclable catalyst for click reactions in water at room temperature

Green Chem., 2017, 19,2506-2509
DOI: 10.1039/C7GC00883J, Communication

Aurelien Adenot, Evan B. Landstrom, Fabrice Gallou, Bruce H. Lipshutz
Nanomicelles housing a terminal alkyne and azide are delivered to ppm Cu-containing nanoparticles that catalyse click reactions in water at rt.

 

Fe/ppm Cu nanoparticles as a recyclable catalyst for click reactions in water at room temperature

Aurélien Adenot,a  Evan B. Landstrom,a  Fabrice Galloub  and  Bruce H. Lipshutz*a 

*Corresponding authors

aDepartment of Chemistry & Biochemistry, University of California, Santa Barbara, USA
E-mail: lipshutz@chem.ucsb.edu

bNovartis Pharma A6, Basel, Switzerland

Abstract

New iron-based nanoparticles doped with ppm levels of CuOAc are capable of catalyzing cycloadditions between alkynes and azides to afford triazole-containing products. These reactions take place in water at ambient temperatures, enabled by the presence of nanomicelles that function as a delivery mechanism. The NPs can be easily recycled within the same reaction vessel. Low levels of residual copper are found in the product.

(2) 1-Benzyl-4-phenyl-1H-1,2,3-triazole. Isolated as a white powdery crystal (99%).

Rf = 0.33 (1:3 EtOAc: hexanes).

NMR 1 H (CDCl3, 500 MHz, δ): 7.79-7.81 (m, 2H), 7.66 (s, 1H), 7.37-7.42 (m, 5H), 7.30-7.33 (m, 3H), 5.59 (s, 2H).

Melting point: 123-125 o C.

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The first continuous flow synthesis of C₈–C₁₆ alkane fuel precursors from biobased platform molecules is reported. TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) was found to be a recyclable and highly efficient organic base catalyst for the aldol condensation of furfural with carbonyl compounds, and the selectivity of mono- or difuryl product can be easily regulated by adjusting the molar ratio of substrates. By means of flow technique, a shorter reaction time, satisfactory output, and continuous preparation are achieved under the present procedure, representing a significant advance over the corresponding batch reaction conditions.

Continuous Microflow Synthesis of Fuel Precursors from Platform Molecules Catalyzed by 1,5,7-Triazabicyclo[4.4.0]dec-5-ene

Tao Shen^†‡, Jingjing Tang^†‡, Chenglun Tang^†‡, Jinglan Wu^†‡, Linfeng Wang^∥, Chenjie Zhu^*†‡§ , and Hanjie Ying^†‡§

^† College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China

^‡National Engineering Technique Research Center for Biotechnology, Nanjing 211816, China

^§Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing 211816, China

^∥State Key Laboratory of Motor Vehicle Biofuel Technology, Nanyang 473000, China

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00141

*E-mail: zhucj@njtech.edu.cn. Phone/Fax: +86 25 58139389.

http://pubs.acs.org/doi/abs/10.1021/acs.oprd.7b00141

 

1-(furan-2-yl)-2-methylpent-1-en-3-one

1a

3-pentanone (100 mmol, 8.6 g) and furfural (100 mmol, 9.6 g) were diluted with MeOH-H2O to 40 mL in stream 1, catalyst TBD (10 mmol, 1.39 g) were diluted with MeOH-H2O (v/v = 1/1) to 40 mL in stream 2, the two streams was purged in a 0.2 mL/min speed into slit plate mixer and at the 353 K passed tubing reactor. Finally, the product was extracted with EtOAc and water, the obtained organic layer was evaporated and purified by silica gel flash chromatography (25:1 hexane-EtOAc) to provide the analytically pure product for further characterization, the aqueous phase was collected and reused.According to the general procedure afforded 14.92 g (91%) of product 1a, isolated as pale yellow oil;

 

1H NMR (400 MHz, CD3OD) δ 7.62 (d, J = 1.4 Hz, 1H), 7.29 (s, 1H), 6.71 (d, J = 3.5 Hz, 1H), 6.52 (dd, J = 3.4, 1.8 Hz, 1H), 2.71 (q, J = 7.3 Hz, 2H), 2.05 (s, 3H), 1.04 (t, J = 7.3 Hz, 3H).

 

13C NMR (100 MHz, CD3OD) δ 203.5, 153.0, 145.8, 133.8, 126.8, 116.6, 113.3, 31.1, 13.2, 9.2.

 

  

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Synthesis of 2-substituted quinazolines by CsOH-mediated direct aerobic oxidative cyclocondensation of 2-aminoarylmethanols with nitriles in air

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC00977A, Communication

Song Yao, Kaijing Zhou, Jiabing Wang, Hongen Cao, Lei Yu, Jianzhang Wu, Peihong Qiu, Qing Xu
An atom-efficient synthesis of 2-substituted quinazolines is developed by a CsOH-mediated aerobic oxidative reaction of 2-aminoarylmethanols and nitriles in air.

Synthesis of 2-substituted quinazolines by CsOH-mediated direct aerobic oxidative cyclocondensation of 2-aminoarylmethanols with nitriles in air

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC00977A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

• From the journal:

  Green Chemistry

Synthesis of 2-substituted quinazolines by CsOH-mediated direct aerobic oxidative cyclocondensation of 2-aminoarylmethanols with nitriles in air

Song Yao,ab  Kaijing Zhou,b  Jiabing Wang,a  Hongen Cao,c  Lei Yu,c  Jianzhang Wu,*a  Peihong Qiu*a  and  Qing Xu*abc 

 Author affiliations

*Corresponding authors

aChemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
E-mail: wjzwzmu@163.com, wzqph@163.com
Tel: +86-158-25672558

bCollege of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, P. R. China
E-mail: qing-xu@wzu.edu.cn
Fax: +86-577-86689302
Tel: +86-138-57745327

cInstitute of Pesticide, School of Horticulture and Plant Protection and School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China

Abstract

By using air as the superior oxidant, a highly atom-efficient synthesis of 2-substituted quinazolines is developed by a CsOH-mediated direct aerobic oxidative reaction of the readily available and stable 2-aminoarylmethanols and nitriles. Effectively working as the promoter in the alcohol oxidation, nitrile hydration, and cyclocondensation steps, CsOH is the best base for the reaction. A similar method can also be extended to the synthesis of substituted quinolines starting from methyl ketones instead of nitriles.

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1-[2-(methylsulfanyl)-10H-phenothiazin-10-yl]ethanone

1-[2-(methylsulfanyl)-10H-phenothiazin-10-yl]ethanone (3): Off-white solid, yield. 93% (218 g),

m. p. 223-226 °C.

1H NMR (400 MHz, CDCl3, δ/ppm): 7.49 (d, 1H, arom H, J = 7.6 Hz), 7.46-7.42 (m, 2H, arom H), 7.36-7.32 (m, 2H, arom H), 7.28-7.22 (m, 1H, arom H), 7.13 (dd, 1H, arom H, J = 8.0 Hz and 1.6 Hz), 2.51 (s, 3H, -SCH3), 2.23 (s, 3H, -COCH3).

13C NMR (100 MHz, DMSO-d6, δ/ppm): 168.36, 139.19, 138.52, 137.74, 132.05, 128.07, 127.97, 127.78, 127.44, 127.19, 126.94, 124.60, 124.51, 22.71, 14.88.

MS m/z (ESI): 288.04 (M+H)+.

An efficient, practical, and commercially viable manufacturing process was developed with ≥99.7% purity and 31% overall yield (including four chemical reactions and one recrystallization) for an active pharmaceutical ingredient, called Metopimazine (1), an antiemetic drug used to prevent emesis during chemotherapy. The development of two in situ, one-pot methods in the present synthetic route helped to improve the overall yield of 1 (31%) compared with earlier reports (<15%). For the first time, characterization data of API (1), intermediates, and also possible impurities are presented. The key process issues and challenges were addressed effectively and achieved successfully.

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00052

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NMR EXAMPLES TO LEARN, (E)-5-Phenylpent-2-enal with real (lit) and predict data

(E)-5-Phenylpent-2-enal has the following physical and spectroscopic properties: 

¹H NMR (500 MHz, CDCl₃) δ: 2.66-2.71 (m, 2H), 2.85 (t, J = 7.5 Hz, 2 H), 6.15 (ddt, J = 15.8, 7.8, 1.4 Hz, 1 H), 6.87 (td, J = 15.7, 6.7 Hz, 1 H), 7.20-7.25 (m, 3 H), 7.31-7.34 (m, 2 H), 9.51 (d, J = 7.8 Hz, 1 H). 

¹³C NMR (125 MHz, CDCl₃) δ: 34.3, 34.4, 126.6, 128.5, 128.8, 133.6, 140.4, 157.4, 194.1. 

IR (neat) cm⁻¹: 3064, 3031, 2930, 1685, 1490, 1120. 

HRMS calcd. for C₁₁H₁₂O (MH⁺): 161.0966, found 161.0964. 

GC-MS (EI) m/z (relative intensity), 160 (8%, M⁺), 142 (14%), 129 (12%), 116 (75%), 92 (35%), 91 (100%), 77 (18%), 65 (60%), 51 (21%).

Purity by GC: 97% (t_R = 10.5 min; conditions same as in Note 7).

The material crystallizes in the freezer and has an approximate melting point of -12 to -14 °C.


1H NMR

13 C NMR

1H NMR AND 13C NMR PREDICT COMING.......

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O=C\C=C\CCc1ccccc1

2-pyrazolin-5-one

137-45-1 cas

• 3-Pyrazolin-5-one (8CI)
• Pyrazol-3(or 5)-ol (6CI,7CI)
• 1,2-Dihydro-3H-pyrazol-3-one
• 1,2-Dihydropyrazol-3-one
• 1H-Pyrazol-3-ol

• 1H-Pyrazol-5-ol
• 3-Hydroxypyrazole
• 3-Pyrazoline-5-one
• 3-Pyrazolone
• 4-Pyrazolin-3-one
• NSC 520837
• Pyrazol-3-ol
• Pyrazol-5-ol

Compound 1: Under stirring, to a solution of 5.81 g (50 mmol) of methyl (2E)-3-methoxyacrylate in methanol (5 mL) was hydrazine hydrate (2.75 g, 55 mmol) added and the mixture was refluxed for 1h. Evaporation under reduced pressure to dryness gave 4.13 g (98%) of a slightly yellowish powder, pure according to 1H NMR spectroscopy.

Melting point: 160–162 °C, crystal modifications starting at ~140 °C, (lit. [12] 162–164 °C).

1H-NMR (300 MHz, DMSO-d6, 28 °C, numbering for 1H-pyrazol-3-ol = form D) [13]: δ= 9.82 (br s, 2H, XH); 7.33 (d, 3 J(H5,H4)= 2.3 Hz, 1H, H5); 5.43 (d, 3 J(H4,H5)= 2.3 Hz, 1H, H4).

13C-NMR (75 MHz, DMSO-d6, 28 °C, numbering for 1H-pyrazol-3-ol = form D) [13]: δ= 161.0 (C3, 2 J(C3,H4)= 3.4 Hz, 3 J(C3,H5)= 9.2 Hz); 130.1 (C5, 1 J = 184.0 Hz, 2 J(C5,H4)= 8.2 Hz); 89.3 (C4, 1 J = 175.6 Hz, 2 J(C4,H5)= 8.7 Hz).

15N-NMR (50 MHz, DMSO-d6, 294 K) [14]: δ= –126.5; –192.0.

MS (m/z, %) [15]: 84 (M+ , 100); 55 (24).

Elemental Analysis: Calculated for C3H4N2O (84.08): C, 42.86%; H, 4.80%; N, 33.32%. Found: C, 42.75%; H, 4.65%; N, 33.15%.

References and /Notes:

1. J. Elguero, In 'Comprehensive Heterocyclic Chemistry: Pyrazoles and their Benzo Derivatives', Vol. 5; A. R. Katritzky and C. W. Rees, Eds., Pergamon Press, Oxford, 1984, 167–303.

2. Stanovnik, B.; Svete, J. Product class 1: Pyrazoles. Science of Synthesis 2002, 12, 15–225.

3. Eller, G. A.; Holzer, W. Heterocycles 2004, 63, 2537–2555.

4. Becker, W.; Eller, G. A.; Holzer, W. Synthesis 2005, 2583–2589.

5. Testa, E.; Fontanella, L. Farmaco 1971, 26, 1017–35.

6. Dorn, H.; Zubek, A. J. Prakt. Chem. 1971, 313, 1118–24.

7. Maywald, V.; Steinmetz, A.; Rack, M.; Gotz, N.; Gotz, R.; Henkelmann, J.; Becker, H.; Aiscar Bayeto, PCT Int. Appl. WO 0031042 A2 2000 (Chem. Abstr., 2000, 133, 4655).

8. Holzer, W.; Hallak, L. Heterocycles 2004, 63, 1311–1334, and references cited therein.

9. Cizmarik, J.; Lycka, A. Pharmazie 1988, 43, 794–795.

10. Holzer, W.; Kautsch, C.; Laggner, C.; Claramunt, R. M.; Perez-Torralba, M.; Alkorta, I.; Elguero, J. Molbank 2004 http://www.mdpi.org/molbank/molbank2006/m464.htm 2 von 3 24.02.2009 12:54 Tetrahedron 2004, 60, 6791–6805.

11. Sackus, A.; Holzer, W. manuscript in preparation.

12. Lingens, F.; Schneider-Bernloehr, H. Liebigs Ann. Chem. 1965, 686, 134–144.

13. The spectrum was obtained on a Varian UnityPlus 300 spectrometer (299.95 MHz for 1H, 75.43 MHz for 13C). The center of the solvent signal was used as an internal standard which was related to TMS with δ 2.49 ppm (1H NMR) and δ 39.5 ppm (13C NMR).

14. The spectrum was obtained on a Bruker Avance 500 spectrometer and was referenced against neat, external nitromethane (coaxial capillary). The signals were not unequivocally assigned to the N atoms. 15. The spectrum was obtained on a Shimadzu QP 1000 instrument (EI, 70eV).

Molbank 2006, M464 http://www.mdpi.net/molbank/ A one-step synthesis of pyrazolone Gernot A. Eller* and Wolfgang Holzer Department of Drug Synthesis, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria Phone: +43-1-4277-55634, e-mail: gernot.eller@univie.ac.at *Author to whom correspondence should be addressed

file:///C:/Users/91200291/Downloads/molbank-2006-M464.pdf

NMR IS EASY EVEN MOM CAN TEACH YOU

Patent

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=53A64F5E273ACA610ACAED2A3499BC0F.wapp2nA?docId=WO2015095792&recNum=1&maxRec=&office=&prevFilter=&sortOption=&queryString=&tab=PCTDescription

Synthesis of lH-pyrazol-3-ol

[0223] To a 100 mL round-bottom flask was added methyl (2E)-3-methoxyprop-2-enoate (11.6 g, 99.90 mmol, 1.00 equiv) and methanol (10.0 mL), followed by the addition of hydrazine hydrate (7.8 mL) dropwise with stirring. The resulting solution was stirred for 90 min at 85°C, then concentrated under vacuum to afford crude lH-pyrazol-3-ol as a white solid.

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3-(2-(Benzoylamino)ethyl)-1-phenyl-1H-pyrazol-5-yl benzoate

3-(2-(Benzoylamino)ethyl)-1-phenyl-1H-pyrazol-5-yl benzoate (14). Benzoyl chloride (0.230 mL, 2 mmol) was added to a stirred suspension of amine 6c (276 mg, 1 mmol) in a mixture of anhydrous dichloromethane (10 mL) and 4-methylmorpholine (0.66 mL, 6 mmol) and the mixture was stirred at r.t. for 12 h. Volatile component were evaporated in vacuo and the residue was chromatographed over silica gel (50% EtOAc/hexanes). Fractions containing the products were combined and evaporated in vacuo to give 14. Yellow solid, yield 79%, 326 mg,

mp 109– 112 °C,

IR (νmax, cm –1): 3289, 1753 (C=O), 1632 (C=O), 1445, 1315, 1247, 1076, 760, 697.

1 H NMR (300 MHz, CDCl3), δH 3.01 (2H, t, 3 JHH = 6.3 Hz, CH2CH2NH), 3.86 (2H, q, 3 JHH = 6.0 Hz, CH2CH2NH), 6.36 (1H, s, 4-H of pyrazole), 7.16 (3H, br s, NH), 7.31–7.53 (8H, m, 8H of Ph), 7.59–7.68 (3H, m, 3H of Ph), 7.78–7.83 (2H, m, 2H of Ph), 8.05–8.11 (2H, m, 2H of Ph).

13C NMR (126 MHz, DMSO-d6), δC 28.7, 38.9, 95.8, 122.7, 127.17, 127.23, 127.3, 128.3, 129.25, 129.30, 130.1, 131.1, 134.6, 134.8, 137.6, 144.0, 150.3, 161.8, 166.2. MS, m/z = 412 (MH+ ),

HRMS (ESI), m/z = 412.1649 (MH+ ), C25H22N3O3 requires 412.1656.

Anal. Calcd for C25H21N3O3 (411.45): C, 63.66; H, 6.16; N, 17.13%, Found: C, 63.47; H, 6.30; N, 16.91%.

Synthesis of 3-(2-aminoethyl)-5-hydroxy-1H-pyrazole derivatives

Uroš Grošelj; David Kralj; Jernej Wagger; Georg Dahmann; Branko Stanovnik; Jurij Svete

Skip other details (including permanent urls, DOI, citation information)

Volume 2012, Issue 3, Commemorative Issue in Honor of Prof. Rainer Beckert on the occasion of his 60th anniversary, pp. 49-65

DOI: http://dx.doi.org/10.3998/ark.5550190.0013.305

Visible-light-induced and iron-catalyzed methylation of N-arylacrylamides with dimethyl sulphoxide: a convenient access to 3-ethyl-3-methyl oxindoles

Visible-light-induced and iron-catalyzed methylation of N-arylacrylamides with dimethyl sulphoxide: a convenient access to 3-ethyl-3-methyl oxindoles

Org. Biomol. Chem., 2017, Advance Article
DOI: 10.1039/C7OB00779E, Paper

Zuguang Xie, Pinhua Li, Yu Hu, Ning Xu, Lei Wang
An efficient synthesis of 3-ethyl-3-methyl oxindoles by visible-light promoted and iron-catalyzed difunctionalization of N-arylacrylamides with dimethyl sulphoxide was developed

Visible-light-induced and iron-catalyzed methylation of N-arylacrylamides with dimethyl sulphoxide: a convenient access to 3-ethyl-3-methyl oxindoles

Zuguang Xie,a  Pinhua Li,*a  Yu Hu,a  Ning Xua  and  Lei Wang*ab 

Author affiliations

*Corresponding authors

aDepartment of Chemistry, Huaibei Normal University, Huaibei, P. R. China
E-mail: pphuali@126.com, leiwang@chnu.edu.cn
Fax: +86-561-3090-518
Tel: +86-561-3802-069

bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China

Abstract

A visible-light-induced and iron-catalyzed methylation of arylacrylamides by dimethyl sulphoxide (DMSO) is achieved, leading to 3-ethyl-3-methyl indolin-2-ones in high yields. This reaction tolerates a series of functional groups, such as methoxy, trifluoromethyl, cyano, nitro, acetyl and ethyloxy carbonyl groups. The visible-light promoted radical methylation and arylation of the alkenyl group are involved in this reaction.

 

 

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N-Cyclohexylpiperidine-1-carboxamide

N-Cyclohexylpiperidine-1-carboxamide (7a)

Melting point: 140.2 – 141.4 ºC (lit. 140 – 141 ºC)[S1]

IR (6.3 mg/mL): νmax 3460, 2937, 2856, 1640, 1510, 1451 cm-1 ;

1H NMR: δ 6.00 (br d, J = 7.7 Hz, 1H), 3.37 (tdt, J = 11.0, 7.6, 3.9 Hz, 1H), 3.25 – 3.19 (m, 4H), 1.77 – 1.68 (m, 2H), 1.68 – 1.61 (m, 2H), 1.59 – 1.52 (m, 1H), 1.52 – 1.46 (m, 2H), 1.42 – 1.34 (m, 4H), 1.26 – 1.18 (m, 2H), 1.18 – 1.09 (m, 2H), 1.05 (qt, J = 12.1, 3.3 Hz, 1H) ppm;

13C NMR: δ 156.7, 49.1, 44.3, 33.2, 25.4, 25.3, 25.1, 24.2 ppm;

ESI-HRMS: calcd for C12H23ON2 [M+H]+ : 211.18049; found: 211.18067; delta=0.8 ppm

Synthesis of Urea Derivatives in Two Sequential Continuous-Flow Reactors

Péter Bana† , Ágnes Lakó†, Nóra Zsuzsa Kiss†, Zoltán Béni‡, Áron Szigetvári‡, János Kóti‡, György István Túrós‡, János Éles‡, and István Greiner*‡ 

† Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary

‡ Gedeon Richter Plc., PO Box 27, 1475 Budapest, Hungary

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00019

A continuous-flow system consisting of two sequential microreactors was developed for the synthesis of nonsymmetrically substituted ureas starting from tert-butoxycarbonyl protected amines. Short reaction times could be achieved under mild conditions. In-line FT-IR analytical technique was used to monitor the reaction, including the formation of the isocyanate intermediate, thus allowing optimization of the reagent ratios. The mechanistic role of the applied base was also clarified. The setup was successfully utilized for the synthesis of several urea derivatives including the active pharmaceutical ingredient cariprazine.

References

[S1] Y. Matsumura, Y. Satoh, O. Onomura, T. Maki, J. Org. Chem. 2000, 65, 1549. doi:10.1021/jo991076k

[S2] P. Liu, Z. Wang, X. Hu, European J. Org. Chem. 2012, 2012, 1994. doi:10.1002/ejoc.201101784

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