A Rapid microwave assisted synthesis of novel 1,4-dihydropyridines derivatives under aqueous medium

July-August 2012, Volume 2, No.4

July-August 2012, Volume 2, No.4 Chemistry & Biology Interface, 2012, 2, 4, 206-257 (ISSN: 2249 – 4820)

A Rapid microwave assisted synthesis of novel 1,4-dihydropyridines derivatives under aqueous medium
Shailesh Thakrar, Dhairya Bhavsar, Vicky Jain, Anamik Shah 

Chemistry & Biology Interface, 2012, 2, 4, 220-227 pg 220-227, Department of Chemistry, Saurashtra University, Rajkot-360005, India

 
[Full Text-PDF]

Keywords: 1, 4-dihydro pyridines, Pyrazole aldehyde, One-pot, Microwave, Aqueous medium,
Fe+3 montmorillonite clay K-10, HY-zeolite.
Abstract: An environment friendly synthesis of 1,4-dihydropyridine derivatives was developed by one pot multi component reaction of pyrazole aldehyde, EAA/MAA, 3-amino crotononitrile and Fe+3 montmorillonite clay K-10/ HY-zeolite under microwave irradiation in aqueous medium. The structures of all synthesized compounds were well characterized by Mass, FT-IR, 1H NMR and elemental analysis.

Methyl 5-cyano-1,4-dihydro-2,6-dimethyl- 4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine- 3-carboxylate (5a): MP: 182-184 oC; IR (cm-1): 3489, 3367, 3198, 2974, 2897, 2332, 2260, 1707, 1660, 1587, 1519, 1435, 1356, 1282, 744, 688. MS: m/z = 426.17; 1H NMR (DMSO-d6) δ ppm: 2.14(s, 6H), 2.58(s, 3H), 4.91(s, 1H), 6.91-6.99(d, 2H), 7.20-7.22(t, 2H), 7.29-7.31(t, 1H), 7.45-7.49(t, 2H), 7.60-7.62(d, 1H), 7.71-7.73(d, 2H), 7.95(s, 1H), 8.74(s, 1H). MS: m/z: 410.17; Anal. Calcd. for C25H22N4O2: C, 73.15; H, 5.40; N,13.65; O,7.80; Found: C, 73.06; H, 5.36; N, 13.61; O,7.79(%).

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

Lewis acid-catalyzed 2-arylquinazoline formation from N′-arylbenzimidamides and paraformaldehyde

2-phenylquinazoline (2a, CAS: 25855-20-3)[2]

1 H NMR (400 MHz, CDCl3, ppm) δ 9.48 (s, 1H), 8.63-8.60 (m, 2H), 8.11-8.09 (m, 1H), 7.95-7.89 (m, 2H), 7.64-7.60 (m, 1H), 7.57-7.49 (m, 3H);

13C NMR (100 MHz, CDCl3, ppm) δ 161.1, 160.5, 150.8, 138.0, 134.1, 130.6, 128.6, 128.6, 128.6, 127.2, 127.1, 123.6 ;

MS (EI) ) m/z (%) 206, 197, 179, 105 (100), 77.

Wang, H. M.; Chen, H.; Chen, Y.; Deng, G. J. Org. Biomol. Chem. 2014, 12, 7792

2-phenylquinazoline

Lewis acid-catalyzed 2-arylquinazoline formation from N[prime or minute]-arylbenzimidamides and paraformaldehyde

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC02319C, Communication

Xiufang Cheng, Huamin Wang, Fuhong Xiao, Guo-Jun Deng
An efficient procedure for the synthesis of 2-arylquinazolines from N[prime or minute]-arylbenzimidamides has been developed under transition-metal-free conditions.

An efficient procedure for the synthesis of 2-arylquinazolines from N′-arylbenzimidamides has been developed under transition-metal-free conditions. In this process, stable and low-toxicity paraformaldehyde was used as the carbon source. A broad range of functional groups were well tolerated in this reaction system.

Lewis acid-catalyzed 2-arylquinazoline formation from N′-arylbenzimidamides and paraformaldehyde

Xiufang Cheng,^a   Huamin Wang,^a   Fuhong Xiao*^a and  Guo-Jun Deng*^a  

Hide Affiliations

*

Corresponding authors

^a

Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China
E-mail: gjdeng@xtu.edu.cn, fhxiao@xtu.edu.cn
Fax: (+86)0731-5829-2251
Tel: (+86)0731-5829-8280

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02319Chttp://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC02319C?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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

Dibenzyl disulfide and dibenzyl sulphide

Dibenzyl disulfide

(150-60-7)

COSY PREDICT

¹HNMR predict

1H NMR

13 C NMR PREDICT

13c NMR

Dibenzyl sulphide

M.Wt	214.33
Formula	C14H14S
CAS No.	538-74-9
Synonyms	Benzyl sulfide; dibenzylsulfane

a) GC-MS: Quantification of organic phase were performed on GC-FID (Agilent GC 7890B) by using a capillary column DB-5MS, 2 m x 3 mm, coupled with flame ionization detector. The product was further confirmed by GC-MS (Agilent 5977A)

///////////

Bromoclenbuterol

Bromoclenbuterol

Bromoclenbuterol; CAS 37153-52-9; Chlorbrombuterol; AC1MC7W8;
Molecular Formula:	C12H18BrClN2O
Molecular Weight:	321.64112 g/mol

CLIP

http://dx.doi.org/10.1016/j.chroma.2012.08.031

Journal of Chromatography A

Volume 1258, 5 October 2012, Pages 55–65

 

Wide-range screening of banned veterinary drugs in urine by ultra high liquid chromatography coupled to high-resolution mass spectrometry

• Nuria León^a,
• Marta Roca^a,
• Carmen Igualada^a,
• Claudia P.B. Martins^b,
• Agustín Pastor^c,
• Vicent Yusá^a, ,

• ^a Center for Public Health Research (CSISP), Avda de Cataluña 21, 46020 Valencia, Spain
• ^b Thermo Fisher Scientific, Barcelona, Spain
• ^c Analytical Chemistry Department, Universidad de Valencia, Edifici Jeroni Muñoz, 50, Dr. Moliner, 46100 Burjassot, Valencia, Spain

CLIP

Synthesis and Characterization of Bromoclenbuterol

Ravi Kumar Kannasani^*, Srinivasa Reddy Battula, Suresh Babu Sannithi, Sreenu Mula and Venkata Babu VV

R&D Division, RA Chem Pharma Limited, API, Hyderabad, Telangana, India

*Corresponding Author:

Ravi Kumar Kannasani
R&D Division, RA Chem Pharma Limited
API, Prasanth Nagar, Hyderabad, Telangana, India
Tel: +919000443184
E-mail: kannasani.ravi@rachempharma.com

http://www.omicsonline.org/open-access/synthesis-and-characterization-of-bromoclenbuterol-2161-0444-1000397.php?aid=79341

Citation: Kannasani RK, Battula SR, Sannithi SB, Mula S, Babu VVV (2016) Synthesis and Characterization of Bromoclenbuterol. Med Chem (Los Angeles) 6:546-549. doi:10.4172/2161-0444.1000397

4-Amino acetophenone (1) was reacted with N-Chlorosuccinimide in 1N HCl to afford 4-amino-3-chloro acetophenone (7), which was reacted with bromine to give 1-(4-amino-3-bromo-5-chlorophenyl)- 2-bromoethanone (8). The obtained bromo compound was reacted with tertiay -butyl amine to afford 2-(tert-butylamino)-1-(4-amino-3- bromo-5-chlorophenyl)ethanone (9), which was reduced with sodium borohydride in methanol to give bromoclenbuterol compound (10). The synthesized bromoclenbuterol structure was confirmed by ¹H NMR, ¹³C NMR, IR and mass spectra.

1-(4-Amino-3-chlorophenyl)ethanone (7)

To a stirred solution of 1N HCl (1500 ml) was added 4-amino acetophenone (1) (200 gm, 1.48 mole) and N-Chloro succinimide (50 gm, 0.37 mole) at room temperature, and stirring continued for 3 hrs at 25-30°C. After maintenance undissolved material was filtered from the reaction mixture, total filtrate was taken and extracted with ethyl acetate, dried over sodium sulfate and evaporated under vacuum to get crude. Crude material was dissolve in ethyl acetate, titrated with EA-HCl and stirred for 15-30 min to get precipitation. The obtained precipitate was filtered and washed with ethyl acetate, and this acidic titration operation was repeated 2 times to get mono chloro compound as solid material, this solid material was neutralized with sodium carbonate solution in aqueous condition and further purified by using recrystlliaztion technique in ethyl acetate to get 68 gm (yield-27%) 3-chloro-4-amino acetophenone (7) (mono chloro compound), as light brown colored solid with 98.66% HPLC purity (124 gm of unreacted 4-amino acetophenone obtained from aqueous layer).

1-(4-Amino-3-bromo-5-chlorophenyl)-2-bromoethanone (8)

To a stirred solution of 3-chloro-4-amino acetophenone (7) (14 gm, 0.082 mole) in chloroform (140 ml) was added bromine (26.24 gm, 0.164 mole) solution slowly at 25-30°C and stirring continued for 6 hrs at same temperature. After completion of the reaction, methanol was added to the reaction mixture and continued the stirring for 30 min at RT. Undissolved material was filtered, the filtrate was distilled up to 50%, remaining mass was cooled to 0-5°C and filtered to give 15 gm (yield-55%) of 1-(4-amino -3-chloro-5-bromo - phenyl) -2-bromo ethanone (8) as light brown color solid with 95.15% HPLC purity.

2-(Tert-butylamino)-1-(4-amino-3-bromo-5-chlorophenyl) ethanone (9)

To a stirred solution of 1-(4-amino -3-chloro-5-bromo - phenyl) -2-bromo ethanone (8) (8 gm, 0.024 mole) in chloroform (50 ml) was added catalytic amount of potassium iodide (0.1 gm, 0.0006 mole) and tertiary butyl amine (5.2 gm, 0.072 mole) at 0-5°C and stirring was continued for 24 hrs at 0-5°C. After completion of the reaction, undissolved salts were filtered, the filtrate was distilled under vacuum to get crude solid material, which was triturated with hexane to give 6 gm (yield-76%) of 1-(4-amino-3-chloro-5-bromo phenyl)-2-[(1,1- dimethylethyl)amino]ethanone (9) as light pale yellow color solid.

(S)-2-(Tert-butylamino)-1-(4-amino-3-bromo-5- chlorophenyl)ethanol (10)

To a stirred solution of 1-(4-Amino-3-chloro-5-bromo phenyl)- 2-[(1,1-dimethylethyl)amino]ethanone (9) (6 gm, 0.018 mole) in methanol (25 ml) was added sodium borohydride (0.7 gm, 0.018 mole) at 0-5°C. After addition, reaction mixture was slowly allowed to come to room temperature and stirred for 10 hrs at 25-30°C. On completion, reaction mixture was poured in to chilled water, obtained precipitate was filtered, dried and recrystallized in methanol to give 5 gm (yield-82%) of 1RS-1-(4-amino -3-bromo-5-chloro phenyl) -2-[(1,1-dimethyl ethyl)amino ethanol (or) Bromo clenbuterol (10) as off-white solid. HPLC purity-98.80%,

1H NMR (CDCl₃): δ 7.35 (d, 1H, J=1.2 Hz), 7.23 (d, 1H, J=1.6 Hz), 4.45 (br s, 2H), 4.42 (dd, 1H, J=9.2, 3.6 Hz), 2.84 (dd, 1H, J=11.6, 3.6 Hz), 2.50 (dd, 1H, J=12.0, 9.2 Hz), 1.10 (s, 9H).

¹³C NMR (CDCl₃): 140.12, 133.93, 128.46, 126.05, 119.16, 109.08, 70.94, 50.33, 50.05, 29.15.

IR (KBr, Cm^-1): 3465.99, 3320.19, 2965.04, 1623.40, 1483.88, 1219.17, 758.77, 630.41.

Mass: (m/z)-323.01 (M⁺² peak).

References

1. International Conference on Harmonization (ICH) Guidelines (2002) Q3A (R) Impurities in New Drug Substances.
2. ICH (2006) Impurities in New Drug Products. Q3B (R1).
3. Srinivasulu R, Ravi Kumar K, Nageswararao K (2016) Synthesis of 3,4-dihydropyrimidin-2(1H)-ones using camphor sulfonic acid as a catalyst under solvent-free conditions. Derpharma chemica 8: 375-379.
4. Antuna AZ, Ivan L, Pablo RG, Julio R, Jose, et al. (2011) V. Tetrahedron 67: 5577-5581.
5. Ehrhardt JD (1990) Synthesis of nonadeutero-clenbuterol. Journal of labeled compounds and radiopharmaceuticals 28: 725-729.
6. Drabb TW (1990) Method for the preparation of 4'-(substituted)-amino-2-(substituted) Amino-3’,5'-dichloroacetophenone and salts thereof Trenton. NJ Patent: US4906781A.
7. Bentley TJ (1984) Method for the preparation of 1-(4'-amino-3',5'-dichlorophenyl)-2-alkyl(or dialkyl)aminoethanols. US4461914 A.

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

2,3,4,4a,5,6-hexahydro-1H-pyrido[1,2-a]quinolone (R)-7

1H NMR (500 MHz, CDCl3): δ 7.82 (br s, 1H), 7.28-7.34 (m, 2H), 7.22-7.24 (m, 1H), 3.87 (m, 1H), 3.56 (m, 1H), 3.32 (m, 1H), 3.00-3.03 (m, 2H), 2.46-2.74 (m, 3H), 1.65-2.05 (m, 5H);

13C NMR (100 MHz, CDCl3): δ 137.6, 130.4, 129.2, 127.9, 124.1, 55.9, 54.5, 27.3, 25.2, 22.9, 20.3, 17.1;

Enantiomeric excess was determined by SFC: Chiralpak OD-3, 4.6 mm x 150 mm, particle size: 3 μm, temperature: 30 ºC, A: CO2, B: ethanol with 0.2% of isobutylamine, isocratic: A/B: 95/5, v/v, flow rate 3.0 mL/min.

HRMS (ESI) [M+H]+ m/z calcd for [C13H18N]+ is 188.1361 found 188.1429.

Synthesis of Enantioenriched 2‐Alkyl Piperidine Derivatives through
Asymmetric Reduction of Pyridinium Salts
Bo Qu,* Hari P. R. Mangunuru, Xudong Wei, Keith R. Fandrick, Jean-Nicolas Desrosiers, Joshua D.
Sieber, Dmitry Kurouski, Nizar Haddad, Lalith P. Samankumara, Heewon Lee, Jolaine Savoie, Shengli
Ma, Nelu Grinberg, Max Sarvestani, Nathan K. Yee, Jinhua J. Song and Chris H. Senanayake
Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road,
Ridgefield, CT 06877 USA
/////////////

N-(4-methylphenyl)-3-exo-(4-methoxybenzyl)tricyclo[3.2.1.02,4]octane-6,7-end o-dicarboximide

N-(4-methylphenyl)-3-exo-(4-methoxybenzyl)tricyclo[3.2.1.02,4]octane-6,7-end o-dicarboximide

petroleum ether/EtOAc (10/1→3/1) to give white solid, 185.8 mg, 96 % yield. Mp: 193-195 oC; 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 3.81 (s, 3H), 3.21 (s, 2H), 2.99 (s, 2H), 2.46 (d, J = 6.4 Hz, 2H), 2.40 (s, 3H), 1.40 (d, J = 11.2 Hz, 1H), 1.22 (t, J = 6.4 Hz, 1H), 1.07 (d, J = 10.8 Hz, 1H), 0.92 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 177.2, 157.9, 138.7, 132.3, 129.8, 129.4, 129.2, 126.4, 113.6, 55.1, 49.3, 39.0, 35.8, 31.7, 21.2, 17.9, 14.0; HRMS (EI) calcd. for C25H25NO3 [M+ ]: 387.1834, found: 387.1840

Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study Jiangang Mao, †,‡ Hujun Xie,§Weiliang Bao*,† †Department of Chemistry, Zhejiang University, Hangzhou 310028, Zhejiang, P. R. China ‡School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, 86 Hongqi Avenue, Ganzhou 341000, Jiangxi, P. R. China §School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310035 Zhejiang, P.R. China E-mail: wlbao@zju.edu.cn

Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study

Jiangang Mao†‡, Hujun Xie§, and Weiliang Bao*†

† Department of Chemistry, Zhejiang University, Hangzhou 310028, Zhejiang, P.R. China

‡ School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, Jiangxi, P.R. China

§ School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, Zhejiang P.R. China

Org. Lett., 2015, 17 (15), pp 3678–3681

DOI: 10.1021/acs.orglett.5b01603

*E-mail: wlbao@zju.edu.cn.

Abstract

An unusual methylcyclopropanation from [2 + 1] cycloadditions of vinyl bromides to norbornenes catalyzed by Pd(OAc)2/PPh3 in the presence of CH3ONa and CH3OH has been established. A methylcyclopropane subunit was installed by a 3-fold domino procedure involving a key protonation course. Preliminary deuterium-labeling studies revealed that the proton came from methyl of CH3OH and also exposed an additional hydrogen/deuterium exchange process. These two proton-concerned reactions were fully chemoselective.

http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01603

J. Mao, H. Xie, W. Bao, Org. Lett. 2015, 17, 3678 – 3681

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

Cookson’s Dione

• 
  
• CAS No.: 2958-72-7
• Cookson's dione   
• Formula: C11H10O2
• Molecular Weight: 174.19600

Cookson’s Dione

125 W Batch Reaction
A solution of Diels Alder adduct 3[3] (2.61 g, 15 mmol) in degassed EtOAc (150 ml) was irradiated with a pre-warmed 125 W medium pressure mercury lamp in a 150 ml batch reactor equipped with a
Pyrex immersion well for 15 min. The solvent was removed in vacuo and chromatography on silica
(40% EtOAc in hexane to 100% EtOAc) yielded Cookson’s dione 4 as an off-white solid (2.38 g, 91%)


1.5 kW Flow Reaction
A solution of Diels Alder adduct 3 (436 g, 2.5 mol) in degassed EtOAc (0.5 M) was irradiated with the firefly reactor fitted with a Pyrex inner filter and lamp at 1.5 kW at 36 ml/min. The mixture was
concentrated in vacuo to a slurry to which was added hexane. The mixture was filtered, washing
with petroleum ether and the solid dried to give pure Cookson’s dione 4 as an off-white crystalline
solid (387 g, 89%): m.p. 242 - 243°C;

δH (400 MHz, CDCl3) 3.19 – 3.14 (2H, m, 2×CH), 2.95 – 2.90 (2H,m, 2×CH), 2.82 – 2.78 (2H, m, 2×CH), 2.72 – 2.68 (2H, m, 2×CH), 2.04 (1H, app. d, J = 11.4 Hz, CHH),
1.88 (1H, app. d, J = 11.4 Hz, CHH);

 δC (100 MHz, CDCl3) 212. 2 (2×C), 54.9 (2×CH), 44.8 (2×CH), 43.9 (2×CH), 40.6 (CH2), 38.9 (2×CH)

SMILES O=C2[C@@H]1[C@@H]3C[C@@H]4[C@H]1C(=O)[C@H]5[C@H]2[C@H]3[C@H]45

Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study

Jiangang Mao†‡, Hujun Xie§, and Weiliang Bao*†

† Department of Chemistry, Zhejiang University, Hangzhou 310028, Zhejiang, P.R. China

‡ School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, Jiangxi, P.R. China

§ School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, Zhejiang P.R. China

Org. Lett., 2015, 17 (15), pp 3678–3681

DOI: 10.1021/acs.orglett.5b01603

*E-mail: wlbao@zju.edu.cn.

Abstract

An unusual methylcyclopropanation from [2 + 1] cycloadditions of vinyl bromides to norbornenes catalyzed by Pd(OAc)2/PPh3 in the presence of CH3ONa and CH3OH has been established. A methylcyclopropane subunit was installed by a 3-fold domino procedure involving a key protonation course. Preliminary deuterium-labeling studies revealed that the proton came from methyl of CH3OH and also exposed an additional hydrogen/deuterium exchange process. These two proton-concerned reactions were fully chemoselective.

http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01603

J. Mao, H. Xie, W. Bao, Org. Lett. 2015, 17, 3678 – 3681



Paper

http://www.mdpi.com/1420-3049/12/2/271/htm

Molecules 2007, 12(2), 271-282; doi:10.3390/12020271

Full Paper

Synthesis and Biological Evaluation of Rigid Polycyclic Derivatives of the Diels-Alder Adduct Tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione

Felicia Megumi Ito 1, Jacqueline Marques Petroni 1, Dênis Pires de Lima 1, Adilson Beatriz 1,*, Maria Rita Marques 2, Manoel Odorico de Moraes 3, Letícia Veras Costa-Lotufo 3, Raquel  Carvalho Montenegro 3, Hemerson Iury Ferreira Magalhães 3 and Cláudia do Ó Pessoa 3

1

Department of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, 

MS, Brazil,,

2

Department of Morphophysiology, Federal University of Mato Grosso do Sul, 

Campo Grande, MS, Brazil

3

Department of Physiology and Pharmacology, Federal University of Ceará, 

Fortaleza, CE, Brazil,,,

*

Author to whom correspondence should be addressed;

 Homepage: http://www.dqi.ufms.br/~lp4/adilson.htm.

1. Cookson, R.C.; Grundwell, E.; Hudec, J. Synthesis of cage-like molecules 
2. by irradiation of Diels-Alder adducts. Chem. Ind. (London) 1958, 1003–1004. [Google Scholar]

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