Continuous niobium phosphate catalysed Skraup reaction for quinoline synthesis from solketal

 

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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

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str4

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

Author affiliations

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.

 

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

Author affiliations

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 Open Access
Creative Commons Licence  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).

 

 

/////////////Cellulose acetate,  5-acetoxymethylfurfural,  biomass

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

Author affiliations

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.

Graphical abstract: Synthesis of ureas in the bio-alternative solvent Cyrene
. References 1 Y. Wei, J. Liu, S. Lin, H. Ding, F. Liang and B. Zhao, Org. Lett., 2010, 12, 4220-4223.
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The greening of peptide synthesis

 

The greening of peptide synthesis

Abstract

The synthesis of peptides by amide bond formation between suitably protected amino acids is a fundamental part of the drug discovery process. However, the required coupling and deprotection reactions are routinely carried out in dichloromethane and DMF, both of which have serious toxicity concerns and generate waste solvent which constitutes the vast majority of the waste generated during peptide synthesis. In this work, propylene carbonate has been shown to be a green polar aprotic solvent which can be used to replace dichloromethane and DMF in both solution- and solid-phase peptide synthesis. Solution-phase chemistry was carried out with Boc/benzyl protecting groups to the tetrapeptide stage, no epimerisation occurred during these syntheses and chemical yields for both coupling and deprotection reactions in propylene carbonate were at least comparable to those obtained in conventional solvents. Solid-phase peptide synthesis was carried out using Fmoc protected amino acids on a ChemMatrix resin and was used to prepare the biologically relevant nonapeptide bradykinin with comparable purity to a sample prepared in DMF.

Graphical abstract: The greening of peptide synthesis
Boc-Ala-Phe-OBn 5a    ref S1
Boc-Ala-OH (324 mg, 1.71 mmol) and HCl.H-Phe-OBn (500 mg, 1.71 mmol) were coupled according to the general coupling procedure. The residue was purified using flash column chromatography (35:65, EtOAc:PE) to give Boc-Ala-Phe-OBn 5a as a white crystalline solid (682 mg, 93%). RF = 0.34 (40:60, EtOAc:PE);
mp 95.6-96.3 °C;
[α]D 23 -27.7 (c 1.0 in MeOH);
IR (Neat) νmax 3347 (m), 3063 (w), 3029 (w), 2928 (m), 2852 (w), 1735 (w), 1684 (w) 1666 (w) and 1521 (s) cm-1;
1H NMR (400 MHz, CDCl3): δ = 7.36-7.31 (m, 3H, ArH), 7.29-7.24 (m, 2H, ArH), 7.26-7.21 (m, 3H, ArH), 7.04-6.97 (m, 2H, ArH), 6.72 (d J 7.7 Hz, 1H, Phe-NH), 5.16-5.10 (m, 1H, Ala-NH), 5.13 (d J 12.1 Hz, 1H, OCH2Ph), 5.07 (d J 12.1 Hz, 1H, OCH2Ph), 4.88 (dt, J 7.7, 5.9 1H, PheNCH), 4.11 (br, 1H, Ala-NCH), 3.13 (dd J 13.9, 6.1 Hz, 1H, CH2Ph), 3.08 (dd J 13.9, 6.1 Hz, 1H, CH2Ph), 1.41 (s, 9H, C(CH3)3), 1.29 (d J 6.6 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3): δ = 172.3 (C=O), 171.2 (C=O), 155.6 (NC=O), 135.7 (ArC), 135.1 (ArC), 129.5 (ArCH), 128.7 (ArCH), 128.6 (ArCH), 127.2 (ArCH), 80.2 (CMe3), 67.4 (OCH2Ph), 53.3 (Phe-NCH), 50.3 (Ala-NCH), 38.0 (CH2Ph), 28.4 (C(CH3)3), 18.5 (CH3);
MS (ESI) m/z 449 [(M+Na)+ , 100]; HRMS (ESI) m/z calculated for C24H30N2O5Na 449.2048 (M+Na)+ , found 449.2047 (0.6 ppm error).
S1 J. Nam, D. Shin, Y. Rew and D. L. Boger, J. Am. Chem. Soc., 2007, 129, 8747–8755; Q. Wang, Y. Wang and M. Kurosu, Org. Lett., 2012, 14, 3372–3375.
General procedure for peptide coupling reactions in PC To a suspension of an N-Boc-amino acid (1.0 eq.) and an amino acid or peptide benzyl ester (1.0 eq.) in PC (5 mL mmol-1), at 0 °C, was added a solution of HOBt (1.1 eq.) and i Pr2EtN (3.0 eq.) in a minimal quantity of PC. EDC (1.1 eq.) was added dropwise and the reaction mixture was allowed to stir at room temperature for 16h. The reaction mixture was then diluted using EtOAc (50 mL) and washed with 1M HClaq (3 × 25 mL), saturated Na2CO3 (3 × 25 mL) and H2O (3 × 25 mL). The organic layer was dried (MgSO4 ), filtered and concentrated in vacuo. Any residual PC was removed via short path distillation. Purification details for each peptide and characterising data are given in the supplementary information. General procedure for Boc deprotections in PC An N-Boc-peptide benzyl ester (1.0 eq.) was dissolved in a minimum amount of PC and trifluoroacetic acid (60 eq.) was added. The reaction mixture was allowed to stir for 3h. at room temperature before being concentrated in vacuo. Any residual PC was removed via short path distillation. Characterising data for each deprotected peptide are given in the supplementary information.
Procedure for Boc deprotection of dipeptide 5a using HCl in PC Boc-Ala-Phe-OBn 5a (50 mg, 0.117 mmol) was dissolved in PC (2.34 mL). MeOH (0.40 mL, 9.8 mmol) was added and the solution cooled to 0 o C. Acetyl chloride (0.67 mL, 9.36 mmol) was added dropwise and the solution allowed to stir at room temperature for 2h. Then, PC was removed by short path distillation. The residue was suspended in Et2O and stirred for 5 minutes before being filtered to give HCl.Ala-Ph-OBn as a white solid (32.4 mg, 76%).
Propylene carbonate 1 has been shown to be a green replacement for reprotoxic amide based solvents which are widely used in peptide synthesis. Both solution- and solidphase peptide synthesis can be carried out in propylene carbonate using acid and base labile amine protecting groups respectively. No significant racemisation of the activated amino acids occurs in propylene carbonate and the viability of solid-phase peptide synthesis in propylene carbonate was demonstrated by the synthesis of the nonapeptide bradykinin.
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Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

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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.

Image result for MOM CAN TEACH YOU NMR

Image result for MOM CAN TEACH YOU NMR

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

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.

Graphical abstract: Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source
Image result for MOM CAN TEACH YOU NMR
////////////http://www.rsc.org/suppdata/c7/qo/c7qo00001d/c7qo00001d1.pdf

A Brønsted acid catalysed enantioselective Biginelli reaction

A Bronsted acid catalysed enantioselective Biginelli reaction

Green Chem., 2017, 19,1529-1535
DOI: 10.1039/C6GC03274E, Paper
Margherita Barbero, Silvano Cadamuro, Stefano Dughera
A chiral derivative of 1,2-benzenedisulfonimide, namely (-)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Biginelli reaction.

A Brønsted acid catalysed enantioselective Biginelli reaction

*Corresponding authors
aDipartimento di Chimica, Università di Torino, C.so Massimo d’Azeglio 48, 10125 Torino, Italy
E-mail: stefano.dughera@unito.it
Green Chem., 2017,19, 1529-1535

DOI: 10.1039/C6GC03274E

A chiral derivative of 1,2-benzenedisulfonimide, namely (−)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Biginelli reaction. In fact the yields of the target dihydropyrimidines were very high (25 examples; average 91%) and enantiomeric excesses were always excellent (14 examples; average 97%). Ultimately, we herein propose a procedure that displays a number of benefits and advantages including the total absence of solvents, mild reaction conditions, relatively short reaction times and stoichiometric reagent ratios. Target dihydropyrimidines are obtained in adequate purity, making further chromatographic purification unnecessary. Moreover, the chiral catalyst was easily recovered from the reaction mixture and reused, without the loss of catalytic activity.
dihydropyrimidine-2-thiones 5
(R)-(-)-Ethyl 6-methyl-4-phenyl-2-thioxo-3,4-dihydropyrimidine-5-carboxylate (5a): pale grey solid (135 mg, 98% yield); mp 201–202 °C ( from EtOH; lit17 200–202 °C). 96.4% Ee (GC connected to a J&W Scientific Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-Omethyl-6-O-t-butyldimethylsilyl)-β-cyclodextrin in DB-1701), tR= 12.11 min (major), tR= 12.54 min (minor); [a]D -65.4 (c 0.1 in MeOH). 1H NMR (200 MHz, DMSO-d6): δ = 10.24 (br s, 1H), 9.55 (br s, 1H), 7.31–7.12 (m, 5H), 5.09 (d, J = 3.9 Hz, 1H), 3.92 (q, J = 7.0 Hz, 2H), 2.21 (s, 3H), 1.01 (t, J = 7.0 Hz, 3H); 13C NMR (50 MHz, DMSO-d6): δ = 174.9, 165.8, 145.7, 129.3, 128.3, 127.0, 101.3, 60.2, 54.7, 17.8, 14.7. MS (m/z, EI): 276 [M+ ] (45), 247 (40), 199 (100). IR (neat) ν (cm−1): 3311 (NH), 3112 (NH), 1665 (CO), 1195 (CS).
Image result for Stefano Dughera

Dughera Dott. Stefano

Tel: 0116707645
Email: stefano.dughera@unito.it
address: Department of Chemistry

Dipartimento di Chimica, Università di Torino, C.so Massimo d’Azeglio 48, 10125 Torino, Italy

R. Fu, Y. Yang, W. Lai, Y. Ma, Z. Chen, J. Zhou, W. Chai, Q. Wang, and R. Yuan, Synth. Comm., 2015, 45, 477.
//////////////Brønsted acid,  catalysed,  enantioselective,  Biginelli reaction, dihydropyrimidine-2-thiones

A two-step efficient preparation of a renewable dicarboxylic acid monomer 5,5[prime or minute]-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose and its application in polyester synthesis

Graphical abstract: A two-step efficient preparation of a renewable dicarboxylic acid monomer 5,5′-[oxybis(methylene)]bis[2-furancarboxylic acid] from d-fructose and its application in polyester synthesis

A two-step efficient preparation of a renewable dicarboxylic acid monomer 5,5[prime or minute]-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose and its application in polyester synthesis

Green Chem., 2017, 19,1570-1575
DOI: 10.1039/C6GC03314H, Paper
Ananda S. Amarasekara, Loc H. Nguyen, Nnaemeka C. Okorie, Saad M. Jamal
A renewable monomer 5,5[prime or minute]-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose.

A two-step efficient preparation of a renewable dicarboxylic acid monomer 5,5′-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose and its application in polyester synthesis

*Corresponding authors
aDepartment of Chemistry, Prairie View A&M University, Prairie View, USA
E-mail: asamarasekara@pvamu.edu
Fax: +1 936 261 3117
Tel: +1 936 261 3107
Green Chem., 2017,19, 1570-1575

DOI: 10.1039/C6GC03314H

D-Fructose was converted to the dialdehyde 5,5′-[oxybis(methylene)]bis[2-furaldehyde] by heating at 110 °C in DMSO with the Dowex 50 W X8 solid acid catalyst in 76% yield without the isolation of the intermediate 5-hydroxymethylfurfural. This dialdehyde was then converted to the dicarboxylic acid monomer, 5,5′-[oxybis(methylene)]bis[2-furancarboxylic acid], using oxygen (1 atm.) and 5% Pt/C catalyst in 1.5 M aqueous NaOH at room temperature in 98% yield. The new dicarboxylic acid monomer can be considered as a renewable resource based alternative to terephthalic acid as demonstrated by the preparation of polyesters with 1,2-ethanediol and 1,4-butanediol in 87–92% yield.

Synthesis of 5,5′-[oxybis(methylene)]bis[2-furancarboxylic acid]

pale yellow crystals. 260 mg, 98 % yield. M.pt. 207-209 °C, Lit. M. pt. 209-210 °C 37 .
IR (ATR) 761, 891, 951, 1029, 1059, 1159, 1208, 1283, 1342, 1424, 1525, 1674, 3128 cm-1
1 H NMR (DMSO-d6 ) δ 3.38 (2H, bs, 2XCOOH), 4.51 (4H, s, 2X-CH2O ), 6.61 (2H, d, J = 3.6 Hz, C-4,4′), 7.15 (2H, d, J = 3.6 Hz, C-3,3′).
13C NMR (DMSO-d6 ) δ 63.8, 112.2, 118.8, 145.3, 155.5, 159.6
37. T. Iseki and T. Sugiura, J. Biochem., 1939, 30, 113-118.
NMR PREDICT
1H NMR PREDICT
13C NMR PREDICT
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Nowruz 2017
Nowruz 2017