Tuesday, 21 March 2017



2-({3-Methyl-6-[(3R)-3-piperidinylamino]-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)-4-fluorobenzonitrile (8)
Mp: 90 °C decomposed.
1H NMR (400 MHz, CD3OD) δ (ppm): 7.85–7.89 (m, 1H), 7.25–7.28 (m, 1H), 6.96–6.99 (m, 1H), 5.37–5.51 (m, 2H), 4.84 (s, 1H), 3.42–3.49 (m, 1H), 3.28 (s, 3H), 3.11–3.15 (m, 1H), 2.89–2.93 (m, 1H), 2.46–2.58 (m, 2H), 1.92–1.95 (m, 1H), 1.48–1.70 (m, 3H).
MS (ESI+): m/z, 358.06 ([M + H]+).

Sunday, 29 January 2017

Synthesis of tetrazines from gem-difluoroalkenes under aerobic conditions at room temperature

Synthesis of tetrazines from gem-difluoroalkenes under aerobic conditions at room temperature

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03494B, Paper
Zheng Fang, Wen-Li Hu, De-Yong Liu, Chu-Yi Yu, Xiang-Guo Hu
A procedure for the synthesis of tetrazines from gem-difluoroalkenes under aerobic conditions has been developed.
An efficient and green procedure for the synthesis of tetrazines has been developed based on an old chemistry reported by Carboni in 1958. Both symmetric and asymmetric 3,6-disubstituted 1,2,4,5-tetrazines can be obtained in moderate to high yields from the corresponding gem-difluoroalkenes under aerobic conditions at room temperature. This work represents a rare example that ambient air is utilized as an oxidant for the synthesis of tetrazines.

Synthesis of tetrazines from gem-difluoroalkenes under aerobic conditions at room temperature

Zheng Fang,a   Wen-Li Hu,a   De-Yong Liu,a  Chu-Yi Yuab and   Xiang-Guo Hu*a  
Corresponding authors
National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, P. R. China
 E-mail: huxiangg@iccas.ac.cn
Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03494B


3,6−bis([1,1'−biphenyl]−4−ylmethyl)−1,2,4,5−tetra zine (3a). (41 mg, 83%). purple solid;

m.p. 200−202°C;

IR(KBr) nmax/cm−1 2924, 2850, 1488, 1451, 1432, 1388, 851, 750;

1 H NMR (400 MHz, CDCl3) 7.55−7.33 (m, 18H), 4.65 (s, 4H).

 13C NMR (100 MHz, CDCl3) δ 169.2, 140.6, 140.4, 134.8, 129.7, 128.8, 127.6, 127.4, 127.1, 40.9;

HRMS (ESI): calcd. for C28H22N4 [M+H]+ 415.19172, found 415.19124.


Wednesday, 25 January 2017

One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles

Hana and co-workers ( Synlett 2010182759−2764) from Genentech have developed a single-step procedure for conversion of 2-nitro aromatic amines to benzimidazoles. Addition of ammonium chloride proved necessary as Fe powder and formic acid alone was ineffective for nitro reduction. These conditions were compatible with a variety of functional groups on the aromatic, including boronate esters. The methodology was also extended to nitro aminopyridines but failed to deliver the desired product with isoxazole or pyrazole reactants.

Mild and General One-Pot Reduction and Cyclization of Aromatic and Heteroaromatic 2-Nitroamines to Bicyclic 2H-Imidazoles

Emily J. Hanan*, Bryan K. Chan, Anthony A. Estrada, Daniel G. Shore, Joseph P. Lyssikatos

*Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA, Email: hanan.emilygene.com
E. J. Hanan, B. K. Chan, A. A. Estrada, D. G. Shore, J. P. Lyssikatos, Synlett2010, 2759-2764.

see article for more reactions
A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles employs formic acid, iron powder, and NH4Cl as additive to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functional groups demonstrates the general utility of this procedure.

see article for more examples
//////////One-Pot, Reductive Cyclisations,  Nitroanilines,  Imidazoles
“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Monday, 23 January 2017


CAS 1161931-51-6
Mp 89.8–92.3 °C.
IR (neat, ATR): 3072 (w), 1482 (s), 1451 (s), 1294 (s), 1294 (s) cm–1.
1H NMR (399 MHz, DMSO-d6) δ 5.12 (s, 2H), 6.81 (td, J = 8.49, 2.77 Hz, 1H), 7.14 (td, J = 7.64, 1.65 Hz, 1H), 7.18 (dd, J = 10.90, 2.82 Hz, 1H), 7.46 (td, J = 7.52, 0.92 Hz, 1H), 7.60 (dd, J = 7.64, 1.41 Hz, 1H), 7.62 (dd, J = 8.66, 6.23 Hz, 1H), 7.92 (dd, J = 7.83, 0.83 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 74.5, 99.2, 102.4 (d, J = 27.1 Hz), 105.8 (d, J = 3.4 Hz), 108.9 (d, J = 22.5 Hz), 128.5, 129.8, 130.3, 133.6 (d, J = 9.9 Hz), 138.0, 139.2, 155.4 (d, J = 10.7 Hz), 162.2 (d, J = 244.3 Hz).
GCMS: m/z [M]+ calcd for C13H9BrFIO: 405.88600; found: 405.88620.
STR1 STR2 STR3 str4

Org. Process Res. Dev., Article ASAP

Sunday, 8 January 2017

Improving the efficiency of the Diels-Alder process by using flow chemistry and zeolite catalysis

Improving the efficiency of the Diels-Alder process by using flow chemistry and zeolite catalysis

Green Chem., 2017, 19,237-248
DOI: 10.1039/C6GC02334G, Paper
S. Seghers, L. Protasova, S. Mullens, J. W. Thybaut, C. V. Stevens
The industrial application of the Diels-Alder reaction for the synthesis of (hetero)cyclic compounds constitutes an important challenge. To tackle the reagent instability problems and corresponding safety issues, the use of a high-pressure and zeolite catalysed microreactor process is presented.

Improving the efficiency of the Diels–Alder process by using flow chemistry and zeolite catalysis

S. Seghers,a   L. Protasova,b   S. Mullens,b  J. W. Thybautc and   C. V. Stevens*a  
*Corresponding authors
SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
 E-mail: chris.stevens@ugent.be
VITO, Vlaamse Instelling voor Technologisch Onderzoek, Boeretang 200, 2400 Mol, Belgium
Laboratory for Chemical Technology, Department of Chemical Engineering and Technical Chemistry, Faculty of Engineering and Architecture, Ghent University, Technologiepark 914, 9052 Ghent, Belgium
Green Chem., 2017,19, 237-248

DOI: 10.1039/C6GC02334G


The industrial application of the Diels–Alder reaction for the atom-efficient synthesis of (hetero)cyclic compounds constitutes an important challenge. Safety and purity concerns, related to the instability of the polymerization prone diene and/or dienophile, limit the scalability of the production capacity of Diels–Alder products in a batch mode. To tackle these problems, the use of a high-pressure continuous microreactor process was considered. In order to increase the yields and the selectivity towards the endo-isomer, commercially available zeolites were used as a heterogeneous catalyst in a microscale packed bed reactor. As a result, a high conversion (≥95%) and endo-selectivity (89 : 11) were reached for the reaction of cyclopentadiene and methyl acrylate, using a 1 : 1 stoichiometry. A throughput of 0.87 g h−1during at least 7 h was reached, corresponding to a 3.5 times higher catalytic productivity and a 14 times higher production of Diels–Alder adducts in comparison to the heterogeneous lab-scale batch process. Catalyst deactivation was hardly observed within this time frame. Moreover, complete regeneration of the zeolite was demonstrated using a straightforward calcination procedure.

//////Diels-Alder,  flow chemistry, zeolite catalysis

Saturday, 7 January 2017

Copper-catalyzed S-methylation of sulfonyl hydrazides with TBHP for the synthesis of methyl sulfones in water

Copper-catalyzed S-methylation of sulfonyl hydrazides with TBHP for the synthesis of methyl sulfones in water

Green Chem., 2017, 19,112-116
DOI: 10.1039/C6GC03142K, Communication
Yu Yang, Yajie Bao, Qianqian Guan, Qi Sun, Zhenggen Zha, Zhiyong Wang
A copper-catalyzed S-methylation of sulfonyl hydrazides with TBHP for the synthesis of methyl sulfones in water.

A copper-catalyzed S-methylation of sulfonyl hydrazides with TBHP was efficiently developed, providing a variety of methyl sulfones with good to excellent yields. The reaction can be carried out in water smoothly without any ligand or additive under mild conditions and this catalyst-in-water can be recycled several times.

Copper-catalyzed S-methylation of sulfonyl hydrazides with TBHP for the synthesis of methyl sulfones in water

Yu Yang,a   Yajie Bao,a   Qianqian Guan,a   Qi Sun,a  Zhenggen Zhaa and   Zhiyong Wang*a  
Corresponding authors
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry & Collaborative Innovation Center of Suzhou Nano Science and Technology, University of Science and Technology of China, Hefei, P. R. China
 E-mail: zwang3@ustc.edu.cn
Fax: (+86) 551-360-3185
Green Chem., 2017,19, 112-116

DOI: 10.1039/C6GC03142K

General procedures for the synthesis of Arylsulfonyl Hydrazides Arylsulfonyl hydrazides 2b-2s were prepared according to the literature procedure.[1] To a solution of an arylsulfonyl chloride (3.0 mmol) in tetrahyrdofuran (15 mL), was added hydrazine monohydrate (375 mg, 7.5 mmol) dropwise under nitrogen at 0 °C. After vigorous stirring for 30 min at 0 °C, the reaction mixture was added ethyl acetate (60 mL), and washed with saturated brine (3 x 10 mL). The organic layer was dried over sodium sulfate, filtered, concentrated and added to hexane (12 mL) over 5 min. The mixture was filtered, and the collected solid was dried in vacuum.

1-methyl-4-(methylsulfonyl)benzene (3aa).[1] The title compound was prepared according to the general procedure and purified by column chromatography (Petroleum Ether: EtOAc = 3:1) to give a white solid (88 % yield).

1H NMR (400 MHz, CDCl3): 7.84-7.82 (d, 2H, J = 8.0 Hz), 7.38- 7.36 (d, 2H, J = 8.0 Hz ), 3.04 (s, 3H), 2.46 ( s, 3H );

13C NMR (100 MHz, CDCl3): 144.7, 137.7, 130.0, 127.3, 44.6, 21.6

Reference [1] G. Yuan, J. Zheng, X. Gao, X. Li, L. Huang, H. Chen and H. Jiang, Chem. Commun., 2012, 48, 7513.

1H NMR (400 MHz, CDCl3): 7.84-7.82 (d, 2H, J = 8.0 Hz), 7.38- 7.36 (d, 2H, J = 8.0 Hz ), 3.04 (s, 3H), 2.46 ( s, 3H );

13C NMR (100 MHz, CDCl3): 144.7, 137.7, 130.0, 127.3, 44.6, 21.6

Image result for 1-methyl-4-(methylsulfonyl)benzene nmr


Wednesday, 4 January 2017

Acid Chloride Negishi Couplings

With the plethora of new and efficient C–C bond-forming reactions available to the organic chemists growing on a monthly basis, one area that suffers is the substrate scope for previously reported examples. In this case Kim and Reike ( Tetrahedron Lett. 2011, 52, 1523−1526) reinvestigate work originally reported by Rovis. Initially Kim performs a small catalyst screen using various commercially available catalysts, resulting in Ni(acac)2 being chosen for the remaining coupling reactions due to the rate of reaction and the isolated yield it facilitated. With a large selection of organozinc reagents via direct insertion developed by Reike, they then apply the developed conditions to 26 examples, all of which gave isolated product in good to excellent yields on gram scale.

Preparation of aryl ketones via Ni-catalyzed Negishi-coupling reactions with acid chlorides


A Ni-catalyst-catalyzed cross-coupling reaction of organozinc reagents with acid chlorides has been successfully developed. Mild reaction conditions were required to complete the coupling reactions affording the corresponding aryl ketones in good to excellent yields.

Graphical abstract

Image for unlabelled figure
A representative procedure of coupling reaction; In a 25 mL round-bottomed flask, Ni(acac)2, (0.06 g, 2 mol%) and 10 mL (5 mmol) of 0.5 M solution of 2- (ehtoxycarbonyl)phenylzinc bromide in THF was added into the flask at room temperature. Next, 6-chloronicotinoyl chloride (0.70 g, 4 mmol) dissolved in 5.0 mL of THF was added. The resulting mixture was refluxed overnight, then cooled down to room temperature. Quenched with saturated NH4Cl solution, then extracted with ethyl acetate (30 mL 3). Combined organics were washed with saturated Na2S2O3 solution and brine. Dried over anhydrous MgSO4. A flash column chromatography (50% EtOAc/50% Heptane) gave 0.78 g of 3g as yellow solid in 68% isolated.
Mp = 48–51 C. 1
H NMR (CDCl3, 500 MHz): d 8.59 (s, 1H), 8.11 (d, 2H, J = 10 Hz), 7.69 (t, 1H, J = 5 Hz), 7.62 (t, 1H, J = 5 Hz), 7.43 (d, 1H, J = 5 Hz), 7.38 (d, 1H, J = 10 Hz), 4.17 (q, 2H, J = 5 10 Hz), 1.19 (t, 3H, J = 10 Hz);
13C NMR (CDCl3, 125 MHz): d 194.8, 165.6, 155.6, 151.2, 140.6, 138.8, 133.0, 131.9, 130.6, 130.4, 129.2, 127.5, 124.6, 61.9, 14.0.
str1 str2 str3 str4