Continuous niobium phosphate catalysed Skraup reaction for quinoline synthesis from solketal

Continuous niobium phosphate catalysed Skraup reaction for quinoline synthesis from solketal
Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03140D, Paper
Jing Jin, Sandro Guidi, Zahra Abada, Zacharias Amara, Maurizio Selva, Michael W. George, Martyn Poliakoff
Solketal is derived from the reaction of acetone with glycerol, a by-product of the biodiesel industry. We demonstrate the use of NbOPO4 as a catalyst for the conversion of solketal and anilines to quinolines

Synthesis of 4-(quinolin-6-yl methyl)aniline (6a)

The reaction was carried out accordingly to the general procedure. The purification of 4-(quinoline-6-yl methyl)aniline 6a was carried out with a gradient of polarity from 80:20 to 30:70 (v/v) of CyHex:AcOEt as eluent. 1H NMR (400 MHz, CDCl3) δ ppm: 8.85 (dd, J=4.3,1.7Hz, 1H), 8.07 (dd, J=8.3,1.8Hz, 1H), 8.01 (d, J=9.2Hz, 1H), 7.58–7.54 (m, 2H), 7.36 (dd, J=8.3,4.2Hz, 1H), 7.02 (d, J=8.3Hz, 2H), 6.67–6.63 (m, 2H), 4.06 (s, 2H). 13C NMR (100 MHz, CDCl3) δ ppm: 149.9, 147.3, 144.9, 140.7, 135.9, 131.4, 130.6, 130.1, 129.5, 128.5, 126.6, 121.2, 115.5, 41.2. HRMS-ESI for C16H15N2 [M+H]+ calculated 235.1235, found 235.1245.

Continuous niobium phosphate catalysed Skraup reaction for quinoline synthesis from solketal

Jing Jin,^a  Sandro Guidi,^ab  Zahra Abada,^a  Zacharias Amara,^ac  Maurizio Selva,^b  Michael W. George^ad  and  Martyn Poliakoff*^a 

Author affiliations

*Corresponding authors

^aSchool of Chemistry, University of Nottingham, University Park, NG7 2RD Nottingham, UK
E-mail: martyn.poliakoff@nottingham.ac.uk

^bDepartment of Molecular Sciences and Nanosystems, Università Ca’ Foscari Venezia Via Torino 155, 30172 Venezia-Mestre, Italy

^cLaboratoire Chimie Moléculaire Génie des procédés chimiques et énergétiques, CNAM, 2 rue Conté, Paris, France

^dDepartment of Chemical and Environmental Engineering, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China

Abstract

Solketal is derived from the reaction of acetone with glycerol, a by-product of the biodiesel industry. We report here the continuous reaction of solketal with anilines over a solid acid niobium phosphate (NbP), for the continuous generation of quinolines in the well-established Skraup reaction. This study shows that NbP can catalyse all the stages of this multistep reaction at 250 °C and 10 MPa pressure, with a selectivity for quinoline of up to 60%. We found that the catalyst eventually deactivates, most probably via a combination of coking and reduction processes but nevertheless we show the promise of this approach. We demonstrate here the application of our approach to synthesize both mono- and bis-quinolines from the commodity chemical, 4,4′-methylenedianiline.

./////////

NOESY experiment of diastereomer 10α (3S, 5R) .......(3S,5R)-3-Benzyl-5-isobutyl-1,3,4,5-tetrahydro-2H-thieno[3,2-e]- [1,4]diazepin-2-one (10α)

NOESY experiment of diastereomer 10α (3S, 5R)
(3S,5R)-3-Benzyl-5-isobutyl-1,3,4,5-tetrahydro-2H-thieno[3,2-e]- [1,4]diazepin-2-one (10α):

Pale yellow solid, 50% (64.0 mg),

m.p. 66.7–67.4 °C.

[α]D 29 = –122.2 (c = 1.0, MeOH).

1 H NMR (CDCl3, 300 MHz): δ = 0.90 (d, J = 6.3 Hz, 3 H), 0.92 (d, J = 6.6 Hz, 3 H), 1.36–1.54 (m, 2 H), 1.81 (m, 1 H), 2.08 (s, 1 H), 3.13 (d, J = 5.1 Hz, 2 H), 3.93 (t, J = 5.1 Hz, 1 H), 4.67 (dd, J = 3.0, J = 9.9 Hz, 1 H), 7.15–7.30 (m, 8 H) ppm.

13C NMR (CDCl3, 75 MHz): δ = 21.48, 23.79, 24.71, 36.81, 42.09, 59.63, 73.76, 111.68, 120.97, 125.09, 126.92, 126.97, 128.70, 129.83 (2 C), 135.11, 136.90, 172.65 ppm.

LC–MS (ESI+): m/z = 315.2 [M + H]+.

HRMS: calcd. for C18H23N2OS 315.1531 [M + H]+; found 315.1531


10.1002/ejoc.201500943

///////////

2-​Thiophenecarboxylic acid, 3-​amino-​, methyl ester

Methyl 3-amino-2-thiophenecarboxylate

• Molecular Formula C6H7NO2S
• Average mass 157.190 Da

2-Thiophenecarboxylic acid, 3-amino-, methyl ester

Cas 22288-78-4

MW 157.19, MF C6 H7 N O2 S

1H NMR CDCL3

13C NMR CDCL3

IR

MASS

1H NMR PREDICT

13C NMR PREDICT

SYNTHESIS 1

By Pokhodylo, Nazariy T. et alFrom Synthetic Communications, 44(7), 1002-1006; 2014

2-Propenenitrile, 3-chloro-, CAS : 871-29-4

SYNTHESIS 2

Rxn NaOMe, MeOH, 0°C

Methyl thioglycolate, CAS: 2365-48-2
C3 H2 Cl N

2-Propenenitrile, 2-chloro- OR 2-chloroacrylonitrile

920-37-6

By Denoyelle, Severine et alFrom European Journal of Organic Chemistry, 2015(32), 7146-7153; 2015

 

 

SYNTHESIS 2 B

Various Annellated Thieno [4,5]imidazo[2,1-b]thiazol-6-acetic Acids

By Schnatt, HeinzFrom No pp.; 1987

Step 1

3-Amino-2-thiophenecarboxylic acid methyl ester, hydrochloride (1):

 

202.5 g (3.75 mol) sodium methoxide was dissolved in 1000 mL absolute methanol and cooled to 20 degC. Subsequently, 159.2 g (1.50 mol) thioglycolic acid methyl ester was added dropwise within 10 minutes, while the temperature was increased to 26 degC. Then 131.3 g (1.50 mol) 2-chloroacrylonitrile was added dropwise within 2.5 hours, while the temperature was kept between 24 and 26 degC by water cooling. It was stirred for 30 minutes. By addition of 130 mL of glacial acetic acid, the mixture was neutralized (pH = 6), filtered over Hyflo and the solution was largely concentrated in vacuum. The residue was partitioned between 800 mL water and 400 mL ether and the aqueous phase was extracted three times with a total of 400 mL ether. The combined organic layers were dried over magnesium sulfate and filtered. Dry HCl gas was passed into this solution for 20 minutes. The precipitate was extracted three times with 100 mL dry ether and dried (50 degC/20 mbar). Yield: 172.3 g of yellowish crystals (60 % of theory). mp 128-129 degC. TLC: solvent: Bz:Et2O = 3:1, Rf = 0.7.

 

Step 2

3-Amino-2-thiophenecarboxylic acid methyl ester (2):

 

291.4 g (1.50 mol) 3-amino-2-thiophencarboxylic acid methyl ester, hydrochloride (1) were suspended in 875 mL methylene chloride and brought to pH = 9 with saturated sodium hydrogen carbonate solution. The reaction mixture was stirred until the completion of gas evolution. The phases were separated and the aqueous phase was extracted with a total of 500 mL methylene chloride. The combined organic layers were dried over sodium sulfate, filtered and evaporated. Yield: 221.7 pale yellow crystals (95 % of theory). mp 65-66 degC. LTC: solvent: Bz:Et2O = 3:1, Rf = 0.7.

 

SYNTHESIS  3

Me thioglycolate and 2-chloroacrylonitrile, and catalyzed by sodium methoxide.

2-chloroacrylonitrile:Me thioglycolate:sodium methoxide=1:1.2:3.3, reaction temp.=25-30°C and t=4h, and using sodium methoxide as Cat, the yield of 3-amino-2-thiophenecarboxylate was 88.2%

Guangdong Huagong, 39(7), 65, 42; 2012

 

Synthesis 4

Synthesis 2010(9): 1428-1430
DOI: 10.1055/s-0029-1218697

R = METHYL,  THEN USE METHANOL AND SODIUM METHOXIDE

 

Paper

 

Bioorganic and Medicinal Chemistry, 2014, vol. 22,  7, p. 2113 - 2122

http://www.sciencedirect.com/science/article/pii/S0968089614001394

 

PAPER

Formation of stabilized organochlorogermylamines by the chelating organic substituent, 3-amino-2-methylthiophoate
Journal of Organometallic Chemistry (1991), 409, (1-2), 131-41.

 

PAPER

Structural modification of diketo acid portion in 1H-benzylindole derivatives HIV-1 integrase inhibitors
Heterocycles (2009), 78, (4), 947-959.

 

PATENT

GB 837086 1960

 

Treating 24.8 g. ClCH2CHClCN with 31.8 g. thioglycollic acid Me ester in the presence of 29.2 g. NaOMe and 280 cc. Et2O gave 72% Me ester of 3-aminothiophene-2-carboxylic acid (I), b0.1 100-2°, m. 65.5°;

 

 

SYNTHESIS

Synthesis of methyl 5-chloro-3-(methylaminosulfonyl)thiophene-2-carboxylate
Faming Zhuanli Shenqing Gongkai Shuomingshu (2008),

NaOMe, MeOH, < 20°C; 30-60 min, < 20°C

10-15°C; 4 h, 10-15°C, ..........H2O, cooled

 

1.  "PhysProp" data were obtained from Syracuse Research Corporation of Syracuse, New York (US)

Bp 101 deg cent

1. ( GB 837086 1960 MP 65.5 °C
2.  Fiesselmann, Hans; DE 1055007 1959 
3.  Ferro, Stefania; Heterocycles 2009, V78(4), Pg947-959
4.  Shi, Jie-hua; Zhejiang Gongye Daxue Xuebao 2004, Vol32(1), Pg25-28 
5.  Takahashi, Tamotsu; JP 2003146986 A 2003 
6.  Huddleston, Patrick R.; Synthetic Communications 1979, Vol9(8), Pg731-4 

 

///////

Cellulose acetate as a convenient intermediate for the preparation of 5-acetoxymethylfurfural from biomass

Cellulose acetate as a convenient intermediate for the preparation of 5-acetoxymethylfurfural from biomass

Llorenç Gavilàab  and  Davide Esposito*a 

Author affiliations

*Corresponding authors

aMax-Planck-Institute of Colloids and Interfaces, D-14424 Potsdam, Germany
E-mail: davide.esposito@mpikg.mpg.de

bDepartment of Chemical Engineering, Universitat Rovira i Virgili, Av Països Catalans 26, Tarragona, Spain

Abstract

5-Acetoxymethylfurfural (AMF) is an important biomass derived platform chemical related to 5-hydroxymethylfurfural. Such furanic compounds can be produced via the hydrolysis of cellulose followed by dehydration of the resulting glucose units. However, the integration of these reactions in a single process remains technically challenging, and the direct use of monosaccharides is often preferred. In this work we report a new method for the synthesis of AMF based on the acetolysis of cellulose acetate in the presence of sulfuric acid. The strategy was optimized for both batch and continuous processing. Furthermore, cellulose acetate prepared by direct wood acetylation could be successfully applied as a precursor, proving the method as a robust solution for integrated biomass processing.

 

Cellulose acetate as a convenient intermediate for the preparation of 5-acetoxymethylfurfural from biomass

Green Chem., 2017, Advance Article

DOI: 10.1039/C7GC00975E, Communication

 Open Access

  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Llorenc Gavila, Davide Esposito
A new method for the synthesis of AMF based on the acetolysis of cellulose acetate is reported. Cellulose acetate prepared by wood acetylation can be applied as a precursor, offering possibilities for integrated biomass processing

 

Cellulose acetate synthesis from cellulose In a round bottom flask, cellulose (2 g, 12 mmol) was suspended in acetic acid (35 mL) and stirred for 1 hour at 55 °C. Thus, a mixture of acetic anhydride (10 mL, 105 mmol) and sulfuric acid (0.4 mL, 7.5 mmol) was slowly added, while the mixture was kept at 55 °C for 2 hours3 . The mixture was thus poured into cold water, the precipitate was filtered, washed and dried at 40 °C in a vacuum oven.

 

Cellulose acetate synthesis from pulp or wood In a round bottom flask, 2 g of wood or pulp were suspended in acetic acid (35 mL) and stirred for 1 hour at 55 °C. Thus, a mixture of acetic anhydride (10 mL, 105 mmol) and sulfuric acid (0.4 mL, 7.5 mmol) was slowly added, while the mixture was kept at 55 °C for 2 hours3 . The mixture was poured into cold water, the precipitate was filtered, washed and dried at 40 °C in a vacuum oven. In order to purify the cellulose acetate, the precipitate was stirred in dichloromethane (30 mL) at 30 °C for 1 hour; afterwards 2/3 of the solvent was evaporated with a rotary evaporator and poured into 20 mL of ethanol, the precipitate was washed with ethanol and dried at 40 °C in a vacuum oven.

 

General procedure for the acetolysis of cellulose acetate Solutions of cellulose acetate in acetic acid were prepared under the approximation that all cellulose acetate is composed of triacetylated anhydroglucose units (molar mass: 288 g/mol). The following molarities (mM) and the number of equivalents are therefore calculated with respect to triacetylated anhydroglucose units. Briefly, the corresponding amount of cellulose acetate to reach a final concentration of 5 g/L (17.4 mM) of cellulose acetate were dissolved in acetic acid and 35 mM of acetic anhydride (2 eq) and 35 mM of acid (2 eq) was added each run, unless otherwise stated. (The same procedure was adapted for non-acetylated cellulose [molar mass: 162 g/mol] as control experiment).

Synthesis of ureas in the bio-alternative solvent Cyrene

 

Synthesis of ureas in the bio-alternative solvent Cyrene

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC00908A, Communication

Liam Mistry, Kopano Mapesa, Thomas W. Bousfield, Jason E. Camp
The bio-alternative solvent Cyrene was shown to be an alternative to toxic oil-derived solvents for the synthesis of ureas.

N-Phenylpyrrolidine-1-carboxamide (6a) 1

 

Method A: To a stirred solution of pyrrolidine (42 µL, 0.5 mmol) in Cyrene (0.5 mL, 1 M) at 0 °C was added phenyl isocyanate (4a, 55 µL, 0.5 mmol). The resultant mixture was allowed to warm to r.t. over 1 h. Water (5 mL) was added and the mixture was stirred for 30 min. The solvent was removed by Buchner filtration and the filtrate was washed with water (60 mL). The residue was dissolved in EtOAc (20 mL), dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to give N-phenylpyrrolidine-1-carboxamide (6a, 76 mg, 80%), as a white solid.

Method B: To a stirred solution of pyrrolidine (42 µL, 0.5 mmol) in Cyrene (0.5 mL, 1 M) at 0 °C was added phenyl isocyanate (4a, 55 µL, 0.5 mmol). The resultant mixture was allowed to warm to r.t. over 1 h. Water (5 mL) was added and the mixture was stirred for 30 min. Water (25 mL) and EtOAc (25 mL) were added. The organic layer was dried over MgSO4 (10.0 g), filtered with the aid of EtOAc (10 mL). Silica gel (100 mg) was added and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel (100 g; EtOAc:hexane, 9:1) to to give N-phenylpyrrolidine-1- carboxamide (6a, 92 mg, 97%), as a white solid. mp. (o C) 133-134 [Lit.1 133-134];

 

IR (neat): 3292, 2971, 2871, 1639, 1532, 1438, 1373, 1239, 759 cm-1 ;

 

1 H NMR (CDCl3, 500 MHz) δ 1.92-1.94 (m, 4H), 3.42-3.45 (m, 4H), 6.29 (br. s, 1H), 6.98-7.01 (m, 1H), 7.24-2.28 (m, 2H), 7.40-7.42 (m, 2H);

 

13C NMR (CDCl3, 125 MHz) δ 25.5, 45.7, 119.5, 122.6, 128.7, 139.2, 153.9;

 

HRMS (ESI) m/z Calcd for [C11H15N2O] + 191.1184; found 191.1179.

Synthesis of ureas in the bio-alternative solvent Cyrene

Liam Mistry,a  Kopano Mapesa,a  Thomas W. Bousfielda  and  Jason E. Camp*a 

Author affiliations

*Corresponding authors

aDepartment of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, UK
E-mail: j.e.camp@hud.ac.uk

Abstract

Cyrene as a bio-alternative solvent: a highly efficient, waste minimizing protocol for the synthesis of ureas from isocyanates and secondary amines in the bio-available solvent Cyrene is reported. This method eliminated the use of toxic solvents, such as DMF, and established a simple work-up procedure for removal of the Cyrene, which led to a 28-fold increase in molar efficiency versus industrial standard protocols.

. References 1 Y. Wei, J. Liu, S. Lin, H. Ding, F. Liang and B. Zhao, Org. Lett., 2010, 12, 4220-4223.

////////////

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.

 

 

//////

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

/////////////