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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Palladium-catalyzed coupling of azoles with 1-aryltriazenes via C–H/C–N cleavage

 

Palladium-catalyzed coupling of azoles with 1-aryltriazenes via C–H/C–N cleavage

Wei-Can Daia  and  Zhong-Xia Wang*ab 

*Corresponding authors

aCAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, P. R. China
E-mail: zxwang@ustc.edu.cn
Tel: +86 551 63603043

bCollaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, P. R. China

Abstract

In the presence of CuCl and ButOLi, PdCl2/dppe catalyzes the reaction of (benzo)oxazoles or (benzo)thiazoles with 1-aryltriazenes to yield arylated products of (benzo)oxazoles or (benzo)thiazoles. Functional groups including F, Cl, CF3, COOEt, CN, OMe, NMe2, Py, and thienyl groups can be tolerated.

Regioselective acylation and carboxylation of [60]fulleroindoline via electrochemical synthesis

    

3a (11.2 mg, 38%) were obtained along with unreacted 1 (1.1 mg, 4%).

1H NMR (400 MHz, CS2/CDCl3) δ 8.39 (d, J = 8.0 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.41 (d, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.04 (d, J = 7.8 Hz, 1H), 5.95 (s, 1H), 2.76 (s, 3H), 2.52 (s, 3H);

13C NMR (100 MHz, CS2/CDCl3, all 1C unless indicated) δ 196.06 (C=O), 167.78 (C=O), 152.39, 152.08, 151.38, 150.04, 149.83, 149.22, 148.81, 148.52, 148.26, 147.93, 147.86, 147.73, 147.36, 147.18, 147.14 (2C), 146.91, 146.86, 146.41, 146.40, 145.99 (2C), 145.95, 145.92, 145.53, 145.37, 145.33, 144.82 (2C), 144.80, 144.72, 144.54, 144.42, 144.31, 144.14, 143.84, 143.65, 143.42, 143.31, 143.05, 142.13, 141.93, 141.79, 141.72 (2C), 141.69, 141.55, 141.35, 141.24, 141.10, 140.63, 140.14, 139.93 (aryl C), 138.84, 137.70, 137.54 (aryl C), 137.47, 137.38, 135.44 (aryl C), 133.14 (aryl C), 129.16 (2C, aryl C), 128.72 (2C, aryl C), 128.61 (aryl C), 125.80 (aryl C), 125.42 (aryl C), 115.11 (aryl C), 83.58 (sp3 -C of C60), 69.89 (sp3 -C of C60), 62.42 (sp3 -C of C60), 56.81 (sp3 -C of C60), 26.84, 22.25;

UV-vis (CHCl3) λmax nm (log ε) 251.0 (5.1), 318.5 (4.6), 403.5 (4.0), 440.0 (3.9), 525.5 (3.2), 703.5 (2.5);

FT-IR ν/cm-1 (KBr) 2922, 2860, 1668, 1599, 1499, 1439, 1366, 1304, 1236, 1180, 1086, 1020, 964, 858, 802, 748, 691, 604, 528;

MALDI-TOF MS m/z calcd for C76H16NO2 [M+H]+ 974.1176, found 974.1165.

Regioselective acylation and carboxylation of [60]fulleroindoline via electrochemical synthesis

Hao-Sheng Lin,a  Yutaka Matsuo,a  Jun-Jie Wanga  and  Guan-Wu Wang*ab 

Author affiliations

Abstract

A regioselective and highly efficient electrochemical method for direct acylation and carboxylation of a [60]fulleroindoline has been developed. By using inexpensive and readily available acyl chlorides and chloroformates, both keto and ester groups can be easily attached onto the fullerene skeleton to afford 1,2,3,16-functionalized [60]fullerene derivatives regioselectively. In addition, a plausible mechanism for the formation of fullerenyl ketones and esters is proposed, and their further transformations under basic and acidic conditions have been investigated.

1,5-bis-(2-furanyl)-1,4-pentadien-3-one (FAF)

A catalytic aldol condensation system enables one pot conversion of biomass saccharides to biofuel intermediates

Huixiang Li,ab  Zhanwei Xu,a  Peifang Yana  and  Z. Conrad Zhang*a 

Author affiliations

*Corresponding authors

aState Key Laboratory of Catalysis, Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
E-mail: zczhang@yahoo.com

bDepartment of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, China

Abstract

Producing bio-intermediates from lignocellulosic biomass with minimal process steps has a far-reaching impact on the biofuel industry. We studied the metal chloride catalyzed aldol condensation of furfural with acetone under conditions compatible with the upstream polysaccharide conversions to furfurals. In situ far infrared spectroscopy (FIR) was applied to guide the screening of aldol condensation catalysts based on the distinguishing characteristics of metal chlorides in their coordination chemistries with carbonyl-containing compounds. NiCl2, CoCl2, CrCl3, VCl3, FeCl3, and CuCl2 were selected as the potential catalysts in this study. The FIR results further helped to rationalize the excellent catalytic performance of VCl3 in furfural condensation with acetone, with 94.7% yield of biofuel intermediates (C8, C13) in 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) solvent. Remarkably, addition of ethanol facilitated the acetal pathway of the condensation reaction, which dramatically increased the desired product selectivity over the furfural pathway. Most significantly, we demonstrate for the first time that VCl3 catalyzed aldol condensation in acidic medium is fully compatible with upstream polysaccharide hydrolysis to monosaccharide and the subsequent monosaccharide isomerization and dehydration to furfurals. Our preliminary results showed that a 44% yield of biofuel intermediates (C8, C13) can be obtained in one-pot conversion of xylose catalyzed by paired metal chlorides, CrCl2 and VCl3. A number of prior works have shown that the biofuel intermediates derived from the one-pot reaction of this work can be readily hydrogenated to biofuels.

1,5-bis-(2-furanyl)-1,4-pentadien-3-one (FAF)

FAF is a yellow solid.1H NMR (400 MHz, CDCl3, TMS) δ 7.51 – 7.46 (m, 4H), 6.92 (d, J = 15.6 Hz, 2H), 6.69 (d, J = 3.4 Hz, 2H), 6.50 – 6.49 (m, 2H);13C NMR (100 MHz, CDCl3) δ 188.1, 151.6, 144.9, 129.2, 123.2, 115.8, 112.6

Synthesis of β-keto sulfones via a multicomponent reaction through sulfonylation and decarboxylation

 

1-Phenyl-2-(phenylsulfonyl)ethan-1-one (2a) 1

1H NMR (400 MHz, CDCl3) δ 7.92 (m, 4H), 7.70 – 7.58 (m, 2H), 7.54 (t, J = 7.6 Hz, 2H), 7.48 (t, J = 7.3 Hz, 2H), 4.74 (s, 2H).

13C NMR (101 MHz, CDCl3) δ 187.9, 138.7, 135.7, 134.4, 134.2, 129.3, 129.2, 128.9, 128.6, 63.4.

References 1. Lu, Q.; Zhang, J.; Peng, P.; Zhang, G.; Huang, Z.; Yi, H.; Millercd, T. J.; Lei, A. Chem. Sci. 2015, 6, 4851.

Synthesis of β-keto sulfones via a multicomponent reaction through sulfonylation and decarboxylation

Jiyao Yu,b  Runyu Mao,a  Qingyu Wanga  and  Jie Wu*ac 

*Corresponding authors

aDepartment of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
E-mail: jie_wu@fudan.edu.cn

bSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, USA

cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China

Abstract

A copper(I)-catalyzed synthesis of β-keto sulfones through a multicomponent reaction of aryldiazonium tetrafluoroborates, 3-arylpropiolic acids, sulfur dioxide, and water was developed. This reaction proceeds through a tandem radical process, and the sulfonyl radical, generated from the combination of aryldiazonium tetrafluoroborates with DABCO·(SO2)2, acts as the key intermediate. The transformation involves sulfonylation and decarboxylation, which allows for the efficient synthesis of the desired β-keto sulfones.

3-allyl-4H-chromen-4-one

3-allyl-4H-chromen-4-one

5b (8.4 g, 45 mmol, 91% yield) as a yellow oil. GC (retention time): 3.571 min

HRMS (EI): m/z calcd for [C12H10O2]: 186,0681 (M+ ); found 186.0657.

1H-NMR (400 MHz, CDCl3 ): δ/ppm = 8.18 (dd, J=8.0, 1.7 Hz, 1H), 7.70 (t, J=1.0, 1H), 7.58 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 7.43 – 7.28 (m, 2H), 5.92 (ddt, J=16.7, 10.1, 6.7 Hz, 1H), 5.22 – 5.04 (m, 2H), 3.20 (dt, J=6.7, 1.3, 2H).

13C NMR (75 MHz, CDCl3 ): δ/ppm = 177.5, 156.6, 152.7, 134.7, 133.5, 126.0, 125.0, 123.9, 123.1, 118.1, 117.2, 29.8.

IR (Diamond-ATR, neat): /cm-1 = 3077.00 (w), 3068.00 (w), 3017.00 (vw), 2970.00 (w), 2941.00 (vw), 2900.00 (w), 1632.00 (s), 1608.00 (s), 1573.00 (m), 1464.00 (s), 1429.00 (m), 1398.00 (s), 1353.00 (s), 1321.00 (m), 1297.00 (m), 1282.00 (m), 1264.00 (w), 1226.00 (w), 1210.00 (m), 1181.00 (m), 1156.00 (s), 1141.00 (s), 1111.00 (m), 1027.00 (w), 1005.00 (m), 961.00 (m), 924.00 (s), 909.00 (s), 896.00 (s), 868.00 (w), 846.00 (s), 802.00 (m), 769.00 (s), 756.00 (vs), 712.00 (m), 690.00 (s).

mp: 34.0 - 36.0 °C

Practical Large-Scale Regioselective Zincation of Chromone Using TMPZnCl·LiCl Triggered by the Presence or Absence of MgCl2

Lydia Klier†, Dorothée S. Ziegler†, René Rahimoff†, Marc Mosrin†‡, and Paul Knochel*† 

† Department Chemie, Ludwig-Maximilians-Universität, Butenandtstrasse. 5-13, 81377 München, Germany

‡ Research & Development, Crop Science, Bayer AG, Alfred-Nobel-Strasse 50, Building 6550, 2.08, 40789 Monheim am Rhein, Germany

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00032

Chromones are efficiently zincated in position C(3) in THF by using the commercially available amide base TMPZnCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl). Additionally, in the presence of a Lewis acid such as MgCl2, zincation using TMPZnCl·LiCl occurs at C(2). These metalation reactions are carried out on a 50 mmol scale, and the metalation selectivities have been compared with the corresponding small-scale reactions (2 mmol). The resulting zinc organometallics undergo smooth reactions with various electrophiles, for example, Pd-catalyzed cross-coupling reactions or Cu-catalyzed acylations or allylations.

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Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

Bis(4-methoxyphenyl)methanone

 

bis(4-methoxyphenyl)methanone (3b) The title product was purified by column chromatography and was obtained in 83% yield (110 mg). Rf = 0.3 (petroleum ether/ethyl acetate 30:1), light yellow oil.

1H NMR (400 MHz, CDCl3) δ (ppm):

7.80 (d, J = 8.8 Hz, 2H),  AROM H ORTHO TO -C=0

6.97 (d, J = 8.8 Hz, 2H),  AROM H ORTHO TO -OCH3

3.89 (s, 6H); TWO -OCH3 GPS

13C NMR (100 MHz, CDCl3) δ (ppm): 194.4, 162.9, 132.2, 132.1, 113.4, 55.5;

IR (KBr): 2957, 1671, 1593, 1260, 1093, 806 cm-1; HRMS(ESI) calc. for (M + Na+ ) 265.0844; found 265.0835.

MOM CAN TEACH YOU NMR

Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

Org. Chem. Front., 2017, 4,569-572
DOI: 10.1039/C7QO00001D, Research Article

Yang Li, Dong-Huai Tu, Bo Wang, Ju-You Lu, Yao-Yu Wang, Zhao-Tie Liu, Zhong-Wen Liu, Jian Lu
By using N,N-dimethylformamide (DMF) as a CO source, nickel-catalyzed carbonylation of arylboronic acids was demonstrated as an efficient and facile protocol for the synthesis of diaryl ketones.

Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

Yang Li,ab  Dong-Huai Tu,a  Bo Wang,a  Ju-You Lu,a  Yao-Yu Wang,b  Zhao-Tie Liu,*c  Zhong-Wen Liuc  and  Jian Lu*a 

*Corresponding authors

aState Key Laboratory of Fluorine & Nitrogen Chemicals, Xi'an Modern Chemistry Research Institute, Xi'an, China
E-mail: lujian204@263.net

bKey Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, China

cKey Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, China
E-mail: ztliu@snnu.edu.cn

Abstract

By using N,N-dimethylformamide (DMF) as a CO source, the cheap metal nickel-catalyzed carbonylation of arylboronic acids was demonstrated as an efficient and facile protocol for the synthesis of diaryl ketones. Results indicated that NiBr2·diglyme was the best pre-catalyst among the investigated transitional metal salts, and excellent yields were achieved via C–H and C–N bond cleavage.

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