A Convenient and “Greener” Synthesis of Methyl Nitroacetate

Abstract Image

Methyl Nitroacetate (2)

Warning: Although no incidents occurred, the intermediates generated, as well as the end product, are energetic and should be handled as if they are explosive materials. It is essential that all reactions be conducted behind a blast shield and that proper protective equipment, including a face shield, be worn at all times during the operation.

A new procedure for the synthesis and isolation of methyl nitroacetate is described. The previously published method required drying the explosive dipotassium salt of nitroacetic acid in a vacuum desiccator, followed by grinding this material into a fine powder with a mortar and pestle prior to esterification. To obtain the desired product, benzene was employed as the extraction solvent, sodium sulfate was used as the drying agent, and two distillations were required. The new procedure eliminates drying and grinding of the explosive dipotassium salt, employs ethyl acetate or dichloromethane as the extraction solvent, eliminates the need for a drying agent, and requires a single distillation to furnish the end product in high yield and purity.

Figure

clear colorless liquid, bp 65 °C (3.9 Torr).

1H NMR (400 MHz; CDCl3) δ 5.18 (s, 2H), 3.87 (s, 3H);

13C NMR (100 MHz, CDCl3) δ 162.5, 76.2, 53.6;

IR (neat): 3041, 2967, 1751, 1557;

Tdec= 251 °C (onset), 272 °C (peak).

NMR PREDICT

Energetics Technology Branch, Energetic Materials Science Branch, U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00093

 

*E-mail: jesse.j.sabatini.civ@mail.mil. Phone: 410-278-0235., *E-mail: pablo.e.guzman2.civ@mail.mil. Phone: 410-278-8608.

 

NMR predict

str1 str2

 

Advertisements

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.

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
aNational Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, P. R. China
E-mail: huxiangg@iccas.ac.cn
bBeijing 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, http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC03494B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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 symmetric 3,6-dialkyl-1,2,4,5−tetrazine(3a−3h)
To a solution of 1,1−difluoroalkenes (1a, 50 mg, 0.27 mmol) in N,N-dimethylformide (DMF,5 mL) was added hydrazine (80%, 35 mg, 1.35 mmol). After stirring at room temperature for 4−6 hours, saturated ammonium chloride (20 mL) was added and the reaction mixture was extracted with dichloromethane (10 mL×3). The organic layer was combined, dried with anhydrous sodium sulfate. The solvent was concentrated and the crude product was dissolved in a suspension of Ethyl Acetate(5 mL) and 10% potassium carbonate solution(wt%, 5 mL) and stirred at room temperature for 24h under air atomerspere until the organic layer turned into amaranth obviously. The organic layer was collected, dried with anhydrous sodium sulfate. The crude product was purified by flash column chromatography[silica gel(#100–200), toluene] to afford the pure 1,2,4,5−tetrazines(3a−3h).
3,6−bis([1,1’−biphenyl]−4−ylmethyl)−1,2,4,5−tetra zine (3a).
str1
(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.

///////tetrazines,  gem-difluoroalkenes, aerobic conditions, room temperature

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

 

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03324E, Communication
Shrikant G. Pharande, Alma Rosa Corrales Escobosa, Rocio Gamez-Montano
An ultrasound accelerated, environmentally benign Ugi-azide based method was developed for the synthesis of 1,5-disubstituted tetrazoles under solvent and catalyst-free conditions.

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

 *Corresponding authors
aDepartamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, Guanajuato, México
E-mail: rociogm@ugto.mx
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03324E,  http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC03324E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A novel, sustainable, endogenous water-triggered, environmentally friendly, high substrate scope, efficient, solvent-free and catalyst-free Ugi-azide based method for the synthesis of 1,5-disubstituted tetrazoles is described.
Shrikant Pharande

Shrikant Pharande

Doctoral student

Research experience

  • Apr 2014–Jun 2014, Research chemist
    TCG Lifesciences · pune
  • Mar 2012–Dec 2013, project assistant
    CSIR – National Chemical Laboratory, Pune · Organic Chemistry Division (NCL)
N-((1-(tert-butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)aniline (4a)
Based on GP, 100 mg 4-Chlorobenzaldehyde (0.71 mmol), 0.065 cm3 aniline (0.71 mmol), 0.080 cm3 ter. Butyl isocyanide (0.71 mmol), and 0.093 cm3 TMS-azide (0.71 mmol) were reacted together to afford 237 mg (97%) as a white solid.
Melting range 144-145oC,
Rf = 0.45 (Hexane-AcOEt = 7/3 V/V),
1H NMR (500 MHz, CDCl3) δ 7.34 – 7.29 (m, 4H), 7.18 – 7.13 (m, 2H), 6.79 – 6.75 (m, 1H), 6.65 (d, J = 7.6 Hz, 2H), 6.11 (d, J = 6.2 Hz, 1H), 4.78 (d, J = 5.6 Hz, 1H), 1.71 (s, 9H);
13C NMR (126 MHz, CDCl3) δ 155.03, 145.54, 136.81, 134.71, 129.62, 129.43, 129.19, 119.64, 114.42, 61.95, 53.93, 30.29;
FT-IR (ATR) νmax/cm-1 3330.5, 3052.5, 2940.9, 1603.6, 1284.1;
HRMS (ESI+): m/z calcd. for C18H20ClN5 + 342.1480, found 342.1474
str1
str2

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

Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material

str1

Abstract Image

Efficient continuous Grignard and lithiation processes were developed to produce one of the key regulatory starting materials for the production of edivoxetine hydrochoride. For the Grignard process, organometallic reagent formation, Bouveault formylation, reduction, and workup steps were run in continuous stirred tank reactors (CSTRs). The lithiation utilized a hybrid approach where plug flow reactors (PFRs) were used for the metal halogen exchange and Bouveault formylation steps, while the reduction and workup steps were performed in CSTRs. Relative to traditional batch processing, both approaches offer significant advantages. Both processes were high-yielding and produced the product in high purity. The two main processes were directly compared from a number of perspectives including reagent and operational safety, fouling potential, process footprint, need for manual operation, and product yield and purity.

Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material

Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, United States
D&M Continuous Solutions, LLC, Greenwood, Indiana 46143, United States
Org. Process Res. Dev., Article ASAP

//////////Flow Grignard,  Lithiation, Screening Tools,  Development, Continuous Processes,  Benzyl Alcohol, Starting Material

Day 10 of the 2016 Doodle Fruit Games! Find out more at g.co/fruit

BENZYL VINYL ETHER

Green Chem., 2016, Advance Article

DOI: 10.1039/C5GC02977E, Communication

Ryosuke Matake, Yusuke Adachi, Hiroshi Matsubara

A convenient preparation of vinyl ethers from alcohols with calcium carbide was developed. This protocol is an alternative to the Favorskii-Reppe reaction without any high pressure device.

Vinyl ethers are important and useful synthetic building blocks. Using a test tube with a screw cap, a convenient preparation of vinyl ethers from alcohols with calcium carbide under superbasic catalytic conditions (KOH/DMSO) was developed. The vinylation of primary and secondary alcohols was successfully achieved, affording the desired products in good yields. The gram-scale preparation of a vinyl ether was also demonstrated. In this reaction, calcium carbide acts as an acetylene source, constituting a safer alternative to acetylene gas.

 F. de Nanteuil, E. Serrano, D. Perrotta and J. Waser, J. Am. Chem. Soc., 2014, 136, 6239.

1H NMR

1H NMR PREDICT using nmrdb , signals may vary , use your discretion to understand sequence

13C NMR

13 C NMR PREDICT

Synthesis of vinyl ethers of alcohols using calcium carbide under superbasic catalytic conditions (KOH/DMSO)

*Corresponding authors

aDepartment of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Japan

Green Chem., 2016, Advance Article

DOI: 10.1039/C5GC02977E

 ////////////////////

Iron bis(oxazoline) complexes in asymmetric catalysis

GA

Iron bis(oxazoline) complexes in asymmetric catalysis

Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. Various chiral iron complexes can be prepared from bis(oxazoline) ligands and be used in asymmetric reactions. This overview charts the development and application of chiral iron bis(oxazoline) and pyridine-2,6-bis(oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis.
Catal. Sci. Technol., 2015, Advance Article
DOI: 10.1039/C5CY01357G, Minireview
Thierry Ollevier
Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. This overview charts the development and application of chiral iron bis(oxazoline) and pyridine-2,6-bis(oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis.

Minireview

Iron bis(oxazoline) complexes in asymmetric catalysis
Thierry Olleviera

aDépartement de chimie, Pavillon Alexandre-Vachon, Université Laval, 1045 avenue de la Médecine, Québec (Qc) G1V 0A6, Canada
E-mail: thierry.ollevier@chm.ulaval.ca
Catal. Sci. Technol., 2015, Advance Article
DOI: 10.1039/C5CY01357G

http://pubs.rsc.org/en/Content/ArticleLanding/2015/CY/C5CY01357G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract

 

 

 

Basics……………

 

Bisoxazoline ligand

In chemistry, bis(oxazoline) ligands (often abbreviated BOX ligands) are a class of privileged chiral ligands containing two oxazoline rings. They are typically C2‑symmetric and exist in a wide variety of forms; with structures based around CH2 or pyridine linkers being particularly common (often generalised BOX and PyBOX respectively). The coordination complexes of bis(oxazoline) ligands are used extensively in asymmetric catalysis.

BOX and PyBOX.png

Synthesis

Further information: Synthesis of oxazoline rings

The synthesis of oxazoline rings is well established and in general proceeded via the cyclisation of a 2‑amino alcohol with any of a number of suitable functional groups. In the case of bis(oxazoline)s, synthesis is most conveniently achieved by using bi-functional starting materials; as this allows both rings to be produced at once. Of the materials suitable, dicarboxylic or dinitrile compounds are the most commonly available and hence the majority bis(oxazoline) ligands are produced from these materials.

BOX and PyBOX general synthesis.png

Part of the success of the BOX and PyBOX motifs lies in their convenient one step synthesis from malononitrile and dipicolinic acid, which are commercially available at low expense. Chirality is introduced with the amino alcohols, as these are prepared from amino acids and hence are chiral (e.g. valinol).

The advantages C2-symmetry

The left hand structure has a C2‑rotational axis whereas the right hand structure is asymmetric. Arrows indicate the theoretical attack trajectories of reagents, identical colours lead to identical transition states (and hence products) with red arrows being disfavoured due to steric repulsion.

In bis(oxazoline) complexes the metal is held close to the stereogenic centres, which will strongly influence the enantioselectivity of any process taking place there. However the C2‑symmetry of the ligand is also important in controlling this enantioselectivity.

While the presence of any symmetry element within a ligand intended for asymmetric induction might appear counterintuitive, asymmetric induction only requires that the ligand be chiral (i.e. have no improper rotation axis); it does not have to be asymmetric (i.e. devoid of any symmetry element). C2‑symmetry actually improves the enantioselectivity of the complex by reducing the number of transition states with a unique geometry. Steric/kinetic factors then usually favour the formation of a single product.[1] The benefits of C2‑symmetry in bis(oxazoline) ligands have been reviewed in depth[2]

In general, for methylene bridged BOX ligands the stereochemical outcome is consistent with a twisted square planar intermediate that was proposed based on related crystal structures.[3][4] The substituent at the oxazoline’s 4-position blocks one enantiotopic face of the substrate, leading to enantioselectivity. This is demonstrated in the following aldol-type reaction,[5] but is applicable to a wide variety of reactions such as Mannich-type reactions,[6] ene reaction,[7] Michael addition,[8] Nazarov cyclization,[9] and hetero-Diels-Alder reaction.[10]

Box Stereochemical model

On the other hand, two-point binding on a Lewis acid bearing the meridially tridentate PyBOX ligand would result in a square pyramidal complex. A study using (benzyloxy)acetaldehyde as the electrophile showed that the stereochemical outcome is consistent with the carbonyl oxygen binding equatorially and the ether oxygen binding axially.[11]

PyBox Stereochemical model

Catalytic applications

Metal complexes incorporating bis(oxazoline) ligands are effective for an wide range of asymmetric catalytic transformations and have been the subject of numerous literature reviews.[12][13][14] The neutral character of bis(oxazoline)s makes them well suited to use with noble metals, with copper complexes being particularly common.[13] Their most important and commonly used applications are in carbon–carbon bond forming reactions.

Carbon–carbon bond forming reactions

bis(oxazoline) ligands have been found to be effective for a range of asymmetric cycloaddition reactions, this began with the very first application of BOX ligands in carbenoid cyclopropanations[15] and has been expanded to include 1,3-Dipolar cycloaddition and Diels-Alder reactions. Bisoxazoline ligands have also been found to be effective for Aldol, Michael and Ene reactions, amongst many others

Evans 1997:[16] BOX assisted Aldol reaction

Aggarwal 1998:[17] BOX assisted Diels-Alder reaction resulting in verbenone synthesis. The final conversion with diphenylphosphoryl azide involves a modified Curtius rearrangement

Other reactions

The success of bis(oxazoline) ligands for carbenoid cyclopropanations led to their application for aziridination. Another common reaction is hydrosilylation, which dates back to the first use of PyBOX ligands.[18] Other niche applications include as fluorination catalysts[19] and for Wacker-type cyclisations.[20]

Nishiyama 1989:[18] Enantioselective hydrosilylation

History

The development of bis(oxazoline) ligands

Oxazoline ligands were first used for asymmetric catalysis in 1984 when Brunner et al. showed a single example, along with a number of Schiff bases, as being effective for enantioselective carbenoid cyclopropanation.[21] Schiff bases were prominent ligands at the time, having been used by Ryōji Noyori during the discovery of asymmetric catalysis in 1968[22] (for which he and William S. Knowles would later be awarded the Nobel Prize in Chemistry). Brunner’s work was influenced by that of Tadatoshi Aratani, who had worked with Noyori,[23] before publishing a number of papers on enantioselective cyclopropanation using Schiff bases.[24][25][26]

In this first usage the oxazoline ligand performed poorly, giving an ee of 4.9% compared to 65.6% from one of the Schiff base ligands. However Brunner reinvestigated oxazoline ligands during research into the monophenylation of diols, leading to the development of chiral pyridine oxazoline ligands, which achieved ee’s of 30.2% in 1986[27] and 45% in 1989.[28] In the same year Pfaltz et al. reported the use of C2‑symmetric semicorrin ligands for enantioselective carbenoid cyclopropanations, achieving impressive results with ee’s of between 92-97%.[29] Reference was made to both Brunner’s and Aratani’s work, however the design of the ligands was also largely based on his earlier work with various macrocycles.[30] A disadvantage of these ligands however, was that they required a multi-step synthesis with a low overall yield of approximately 30%.

C2-symmetric bis(oxazoline) ligands with axial chirality

Brunner’s work led to the development of very first bisoxazolines by Nishiyama et al., who synthesised the first PyBox ligands in 1989. These ligands were used in the hydrosilylation of ketones; achieving ee’s of up to 93%[18] The first BOX ligands where reported a year later by Masamune et al.[15] and were first used in copper catalysed carbenoid cyclopropanation reactions; achieving ee’s of up to 99% with 1% molar loadings. This was a remarkable result for the time and generated significant interest in the BOX motif. As the synthesis of 2-oxazoline rings was already well established at this time (literature reviews in 1949[31] and 1971[32]), research proceeded quickly, with papers from new groups being published within a year.[33][34] and review articles being published by 1996.[35] Today a considerable number of bis(oxazoline) ligands exist; structurally these are still largely based around the classic BOX and PyBOX motifs, however they also include a number of alternative structures, such as axially chiral compounds.[36][37]

 

References

 

 

  1. Ohta, Tetsuo; Ito, Junji; Hori, Kazushige; Kodama, Hidehiko; Furukawa, Isao (2000). “Lanthanide-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to alkenes using 3,3′-bis(2-oxazolyl)-1,1′-bi-2-naphthol (BINOL-Box) ligands”. Journal of Organometallic Chemistry 603 (1): 6–12. doi:10.1016/S0022-328X(00)00024-3.

MORE…………..

Aza-bis(oxazolines) – New Chiral Ligands for Asymmetric Catalysis

M. Glos, O. Reiser, Org. Lett. 2000, 2, 2045-2048
Web edition: http://dx.doi.org/10.1021/ol005947k

graphical abstract

Aza-bis(oxazolines) are introduced as chiral ligands for asymmetric catalysis combining the advantages of easy availability of bis(oxazolines) and backbone variability of aza-semicorrins. Especially, the title ligands could be attached to a polymeric support, which allowed the development of easily recoverable copper(I)-catalysts for asymmetric cyclopropanation reactions.

 

 

 

 

 

 

 

Synthesis of Polymer Bound Azabis(oxazoline) Ligands and their Application in Asymmetric Cyclopropanations

H. Werner, C. I. Herrerí­as, M. Glos, A. Gissibl, J. M. Fraile, I. Pérez, J. A. Mayoral, O. Reiser, Adv. Synth. Catal. 2006, 348, 125-132
Web edition: http://dx.doi.org/10.1002/adsc.200505197

graphical abstract

Aza(bisoxazoline) ligands were attached to various polymeric supports and the resulting immobilized ligands were evaluated in copper(I)-catalyzed asymmetric cyclopropanations. The efficiency of these transformations depends greatly on the polymeric support, on the protocol being applied for the immobilization of the ligands, and on the preparation of the catalysts.

 

 

Cu(II)-Aza(bisoxazoline)-Catalyzed Asymmetric Benzoylations

A. Gissibl, M. G. Finn, O. Reiser, Org. Lett. 2005, 7, 2325-2328
Web edition: http://dx.doi.org/10.1021/ol0505252

graphical abstract

Racemic 1,2-diols and a-hydroxy carbonyl compounds can be asymmetrically benzoylated in a kinetic resolution in the presence of various Cu(II)-azabis(oxazoline) catalysts. A novel bisbenzyl substituted aza(bisoxazoline) ligand proved to be especially effective when immobilized on MeOPEG5000, giving 91 – ≥99% ee in 37 – 49% yield for each of five sequential reactions.

 

The role of binding constant in the efficiency of chiral catalysts immobilized by electrostatic interactions. The case of azabis(oxazoline)-copper complexes

J. M. Fraile, J. I. Garcí­a, C. I. Herrerí­as, A. Mayoral, O. Reiser, A. Socuéllamos, H. Werner, Chem. Eur. J. 2004, 10, 2997-3005
Web edition: http://dx.doi.org/10.1002/chem.200305739

graphical abstract

Azabis(oxazoline)-copper complexes are considerably more stable than the analogous bis(oxazoline)-copper complexes, as shown by theoretical calculations. The enhanced stability allows the efficient immobilization by means of electrostatic interactions with different anionic supports, such as clays and nafion-silica nanocomposites, without the loss of ligand observed with bis(oxazolines). In this way, enantioselectivities around 90% ee are obtained in the cyclopropanation reaction

 

 

Improved Synthesis of Aza-bis(oxazoline) Ligands

H. Werner, R. Vicha, A. Gissibl, O. Reiser, J. Org. Chem. 2003, 68, 10166-10168
Web edition: http://dx.doi.org/10.1021/jo0350920

graphical abstract

A straightforward synthesis of chiral aza-bis(oxazoline) (Azabox) ligands from commercial available aminoalcohols is described. The new protocol allows access to previously reported Azabox ligands in considerably improved yields but also to new derivatives, including non C2-symmetrical ones.

 

Research Group Prof. Reiser

Prof. Dr.
Oliver Reiser

 

Secretary

Phone +941/943-4630
Fax +941/943-4121

http://www-oc.chemie.uni-regensburg.de/reiser/forschung/catalysis_e.php

///////

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Scheme 1

Control experiments.

The ubiquitous oxazoles have attracted more and more attention in both industrial and academic fields for decades. This interest arises from the fact that a variety of natural and synthetic compounds which contain the oxazole substructure exhibit significant biological activities and antiviral properties. Although various synthetic methodologies for synthesis of oxazols have been reported, the development of milder and more general procedure to access oxazoles is still desirable.

Initially, compound A, formed by the substitution reaction of 1a with 2a, which can be transformed following two pathways: (a) I+, generated by the oxidation of iodine, could oxidize A to radical intermediate B, which eliminates one molecular of CO2 to generate radical C, which is further oxidized to imine Dor its isomer E. Subsequently, F is obtained by intramolecular nucleophilic addition of E. Finally, the desired product (3a) is given by deprotonation and oxidation of F; (b) G is formed from the oxidation of A. Then 3a is obtained through H, I, J, K following a process similar to path a.

Scheme 2

Plausible mechanism.

General procedure for the synthesis of polysubstituted oxazoles

1a (105.8 mg, 0.7 mmol), 2a (99.5 mg, 0.5 mmol), I2 (50.8 mg, 0.2 mmol), DMA (2 mL) and TBHP (70% aqueous solution, 1 mmol) were placed in a tube (10 mL) and sealed with a thin film. Then the reaction mixture was stirred at 25°C for 4 h, heated up to 60°C and stirred at this temperature for another 4 h. After that, the resulting mixture was cooled to the room temperature, diluted with water, extracted with ethyl acetate. The organic phase was washed with saturation sodium chloride solution, dried and filtrated. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column separation (petroleum ether:ethyl acetate = 10:1) to give 3a(154.7 mg, 70%) as light yellow solid, mp = 70–72°C.

2,5-diphenyloxazole (3a) [1]

Synthesized according to typical procedure and purified by column chromatography (petroleum ether:ethyl acetate = 10:1) to give light yellow solid (154.7 mg, 70%), mp = 70-72 °C.

1H NMR (300 MHz, CDCl3): δ 8.12-8.09 (m, 2 H), 7.72-7.69 (m, 2 H), 7.50-7.40 (m, 6 H), 7.35-7.24 (m, 1 H).

13C NMR (75 MHz, CDCl3): δ 161.3, 151.4, 130.4, 129.0, 128.9, 128.5, 128.1, 127.6, 126.4, 124.3, 123.6.

HRMS (APCI-FTMS) m/z: [M + H]+ calcd for C15H12NO: 222.0913, Found: 222.0911.

D1 D2

The scope of the reaction. Standard conditions: 0.7 mmol of amino acids (1a1h), 0.5 mmol of2a2j, 0.1 mmol of I2, 1 mmol of TBHP, 2 mL of DMA, were stirred at 25°C for 4 h then slowly raised to 60°C for 4 h. Catalysts amount and isolated yields were based on 2.

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Yunfeng Li, Fengfeng Guo, Zhenggen Zha and Zhiyong Wang*

Zhiyong Wang

Department of Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China

Sustainable Chemical Processes 2013, 1:8  doi:10.1186/2043-7129-1-8

The electronic version of this article is the complete one and can be found online at:http://www.sustainablechemicalprocesses.com/content/1/1/8

ADDITIONAL SPECTRAL DATA FROM NET

WANG Zhiyong(汪志勇)


Ph.D., University of Science and Technology of China (USTC) (1992); M.S., USTC (1989); B.S., Anhui Normal University (1982).

Professor of Chemistry
Department of Chemistry
School of Chemistry and Materials Science
University of Science and Technology of China
Hefei, Anhui 230026, P. R. China

Tel: 86-551-63603185
Fax: 86-551-63603185
E-mail: zwang3@ustc.edu.cn
Personal Homepage:
http://staff.ustc.edu.cn/~zwang3/default.htm

  • RESEARCH INTERESTS
    Research in our group will focus on the general areas of reaction development and chemical synthesis. Our studies will be driven by the discovery of new and useful catalysts. By virtue of the developed organic reactions various organic ligands are synthesized and used as probes in biological progress. Brief summaries of three research directions illustrating these objectives are shown below:
    1) The preparation of heterogeneous catalysts;
    2) The theoretical calculation for the mechanism of organic reactions;
    The application of organic ligands as probes or inhibitors to explore the molecular mechanism of HIV transcription.

    PUBLICATIONS
    http://www.researcherid.com/rid/F-7955-2010

    WANG Zhiyong, Professor
    Name: Zhiyong Wang(汪志勇)
    Born: June, 1962, Anhui, P. R. China
    Address: Department of Chemistry, University of Science and Technology of China, 230026 Hefei, P. R. China
    Tel: 86-551-63603185
    Fax: 86-551-63603185
    E-mail: zwang3@ustc.edu.cn
    EDUCATION AND RESEARCH EXPERIENCE
     1978-1982 B.S., Anhui Normal University
     1982-1986 Lecturer, South Anhui Agricultural College, China
     1986-1989 M.S., University of Science and Technology of China
     1989-1992 Ph.D., University of Science and Technology of China
     1992-1997 Lecturer, Associate Professor, University of Science and Technology of China
     1997-1999 Research Fellow, Tulane University & Brandeis University
     1999-Now Professor of Chemistry, University of Science and Technology of China
    RESEARCH INTERESTS
    1) Organic reactions in aqueous media and development of synthetic methodology;
    2) Supramolecular assembly under the control of organic ligands;
    3) Drug design on the base of PCAF bromodomain.
    CURRENT RESEARCH PROJECTS
    1) Organic reactions in water mediated by nano-metals and its application in asymmetric synthesis, National Natural Science Foundation (2004-2006)
    2) Crystal Engineering under control of organic ligands, Foundation from Education Department of Anhui Province (2003-2005)
    REPRESENTATIVE PUBLICATIONS
    1) C-F. Pan, M. Meze, S. Mujtaba, M. Muller, L. Zeng, J-M. Li, Z-Y. Wang,* M-M. Zhou*
    “Structure-Guided Optimization of Small Molecules Selectively Inhibiting HIV-1 Tat and PCAF Association” J. Med. Chem., 2007, 50, 2285
    2) Y. Xie, Z-P. Yu, X-Y. Huang, Z-Y. Wang,* L-W. Niu, M-K. Teng, J. Li
    “Rational Design on the MOFs Constructed from modified Aromatic Amino Acids”
    Chem. Eur. J., 2007, 13, 9399
    3) Z-H. Zhang, C-F. Pan, Z-Y. Wang* “Synthesis of chromanones: a novel palladium-catalyzed Wacker-type oxidative cyclization involving 1,5-hydride alkyl to palladium migration” Chem. Commun, 2007, 4686
    4) Y. Xie, Y. Yan, H-H. Wu, G-P. Yong, Y. Cui, Z-Y. Wang*, L. Pan, J. Li “Homochiral Metal-organic Coordination Networks from L-Tryptophan” Inorg. Chim. Acta., 2007, 360,1669
    5) Y. Xie, H-H. Wu, G-P. Yong,, Z-Y. Wang*, R. Fan , R-P. Li, G-Q. Pan, Y-C. Tian, L-S. Sheng, L. Pan, J. Li “Synthesis, Crystal Structure, Spectroscopic and Magnetic Properties of Two Cobalt Molecules Constructed from Histidine” J. Mol. Struct., 2007, 833, 88
    6) Z-H. Zhang, Z-Y. Wang* “Diatomite-Supported Pd Nanoparticles: An Efficient Catalyst for Heck and Suzuki Reactions” J. Org. Chem., 2006, 71, 7485
    7) Z-H. Zhang, Z-G. Zha, C-S. Gan, C-F. Pan, Y-Q. Zhou, Z-Y. Wang*, M-M. Zhou* “Catalysis and Regioselectivity of the Aqueous Heck Reaction by Pd(0) Nanoparticles under Ultrasonic Irradiation”
    J. Org. Chem., 2006, 71, 4339

Hefei, Anhui China

////Metal-free,  Synthesis,  Oxazoles, Oxidation,  Decarboxylative cyclization,  α-amino acids