RANITIDINE

Figure 3. (a) Single ion mobility spectrum for ranitidine (m/z 315.2), (b) total ion mobility spectrum, (c) combined mass spectra from ranitidine IMS peak (scans 2029 - 2032), and (d) combined mass spectra from full IMS data (scans 2000 - 2200). 

Ranitidine

 

Ranitidine, sold under the trade name Zantac among others, is a medication that decreases stomach acid production.[1] It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome.[1] There is also tentative evidence of benefit for hives.[2] It can be taken by mouth, by injection into a muscle, or into a vein.[1]

Common side effects include headaches and pain or burning if given by injection. Serious side effects may include liver problems, a slow heart rate, pneumonia, and the potential of masking stomach cancer.[1] It is also linked to an increased risk ofClostridium difficile colitis.[3] It is generally safe in pregnancy. Ranitidine is an H2 histamine receptor antagonist that works by blocking histamine and thus decreasing the amount of acid released by cells of the stomach.[1]

Ranitidine was discovered in 1976 at Glaxo Pharmaceuticals, now a part of GlaxoSmithKline.[4][5] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[6] It is available as a generic medication.[1] The wholesale price in the developing world is about 0.01 to 0.05 USD per pill.[7] In the United States it is about 0.05 USD per dose.[1]

Laboratory Synthesis Of Ranitidine

 

Synthesis Of Ranitidine

 

 

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Ranitidine Synthetic procedure/method of synthesis

The reaction of 5-dimethylaminomethyl-2-furanylmethanol (I) with 2-mercaptoethylamine (II) by means of aqueous HCl gives 2-[[(5-dimethylamino-methyl-2-furanyl)methylthio]ethaneamine (III), which is then condensed with N-methyl-1-methylthio-2-nitrotheneamine (IV) by heating at 120 C. Compound (IV) is obtained by reaction of 1,1-bis(methylthio)-2-nitroethene (V) with methylamine in refluxing ethanol

Ranitidine reference

1. Serradell, M.N.; Blancafort, P.; Casta馿r, J.; Hillier, K.; Ranitidine. Drugs Fut 1979, 4, 9, 663
2.  Price, B.J. et al. (Allen and Hanburys, Ltd.); US 4128658.
3. Price, B.J.; Bradshaw, J.; Clitherow, J.W. (Allen & Hansburys Ltd.); Aminoalkyl furan derivatives.. DE 2734070; FR 2360587; US 4128658 ,DE 2734070; FR 2360587; US 4128658.

PAPER

Synthesis of ranitidine (Zantac) from cellulose-derived 5-(chloromethyl)furfural

Mark Mascal*a and   Saikat Duttaa  

 

*Corresponding authors

aDepartment of Chemistry, University of California Davis, 1 Shields Avenue, Davis, US
E-mail: mascal@chem.ucdavis.edu
Fax: 530-752-8995
Tel: 530-754-5373

Green Chem., 2011,13, 3101-3102

DOI: 10.1039/C1GC15537G

http://pubs.rsc.org/en/content/articlelanding/2011/gc/c1gc15537g#!divAbstract

http://www.rsc.org/suppdata/gc/c1/c1gc15537g/c1gc15537g.pdf

The biomass-derived platform chemical 5-(chloromethyl)furfural is converted into the blockbuster antiulcer drug ranitidine (Zantac) in four steps with an overall 68% isolated yield.

PROCESS

2. Experimental Procedures

5-[[(2-Acetamidoethyl)thio]methyl]furfural 14

Sodium hydride (95%) (103 mg, 4.08 mmol) was added to a solution of Nacetylcysteamine (0.4051 g, 3.40 mmol) in dry THF (20 mL) under argon. The resulting suspension was stirred at RT for 30 min and a solution of CMF 12 (0.4912 g, 3.40 mmol) in dry THF (10 mL) was added dropwise over a 10 min period. The resulting light yellow solution was allowed to stir overnight at RT. The solvent was evaporated and saturated brine (50 mL) was added. The mixture was extracted with CH2Cl2 (2 × 50 mL) and the organic layers were combined and washed with saturated brine (100 mL). The organic layer was dried over Na2SO4. Charcoal (100 mg) was added and the mixture was stirred for 20 min and filtered. The solvent was evaporated to give 14 as a yellow liquid (0.7042 g, 91 %). 1H NMR (CDCl3, 300 MHz) 9.58 (1H, s), 7.21 (1H, d, J = 3.6 Hz), 6.48 (1H, s, br), 5.95 (1H, d, J = 3.6 Hz), 3.79 (2H, s), 3.45 (2H, q, J = 6.3 Hz), 2.72 (2H, t, J = 6.6 Hz), 2.00 (3H, s); 13C NMR (CDCl3, 75 MHz) 23.1, 27.8, 31.7, 38.4, 110.7, 121.9, 152.2, 158.9, 170.7, 177.4; IR (neat) 3298, 3101, 1663, 1548, 1512, 1287, 1022, 772 cm-1; HRMS (ESI): calculated for C10H14O3NS: [M+H]+ 228.0694: found 228.0690.

5-[[(2-Acetamidoethyl)thio]methyl]-N,N-dimethyl-2-furanmethanamine 15

Me2NH (1.0 mL) was added to a solution of 14 (0.2105 g, 0.926 mmol) in dry methanol (20 mL) and the mixture was stirred at RT for 1 h. The resulting red solution was cooled to 0 °C and NaBH4 (98 %) (55 mg, 1.42 mmol) was added over a 5 min period. The mixture was allowed to come to RT and stirred for 30 min. The solvent was evaporated while keeping the bath temperature below 45 °C. The residue was dissolved in CH2Cl(50 mL) and filtered to remove inorganic impurities. The solvent was evaporated to give 15 (0.2145 g, 90 %) as a pale yellow oil. 1H NMR (CDCl3, 300 MHz) 6.42 (1H, s, br), 6.09 (1H, s), 3.67 (2H, s), 3.37 (2H, s), 3.26 (2H, q, J = 6.0 Hz), 2.62 (2H, t, J = 6.4 Hz) 2.21 (6H, s), 1.93 (3H, s); 13C NMR (CDCl3, 75 MHz) 23.5, 28.4, 31.9, 38.7, 45.4, 56.2, 108.4, 109.9, 151.4, 152.1, 170.5; IR (neat) 3273, 2944, 1656, 1545, 1291, 1019, 729 cm- 1 ; HRMS (ESI): calculated for C12H21O2N2S: [M+H]+ 257.1322: found 257.1323.

5-[[(2-aminoethyl)thio]methyl]-N,N-dimethyl-2-furanmethanamine 5

A solution of 15 (0.2473 g, 0.965 mmol) in freshly prepared 2N aq NaOH (10 mL) was heated at reflux for 2 h. The mixture was cooled to RT and extracted with CH2Cl2 (3×30 mL). The organic layers were combined and washed with saturated brine, dried over Na2SO4, and evaporated to give 5 (0.1934 g, 94 %) as a pale yellow oil. 1H NMR (CDCl3, 300 MHz) 6.02 (2H, s), 3.61 (2H, s), 3.33 (2H, s), 2.74 (2H, t, J = 6.3 Hz), 2.52 (2H, t, J = 6.6 Hz), 2.16 (6H, s); 13C NMR (CDCl3, 75 MHz) 28.2, 35.9, 40.9, 45.1, 55.9, 108.1, 109.5, 151.4, 152.1; IR (neat) 3359 cm-1, 2947, 2769, 1559, 1459, 1015, 797 cm-1; HRMS (ESI): calculated for C10H19ON2S: [M+H]+ 215.1212: found 215.1218.

N-[2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro- 1-Ethenediamine (Ranitidine) 1 The experimental procedure is modified from existing literature:2 A solution of 5 (0.1501 g, 0.700 mmol ) in distilled water (10 mL) was added dropwise over a period of 10 min to a suspension of 1-methylthio-1-methylamino-2-nitroethylene 7 (0.1041 g, 0.703 mmol) in distilled water (5 mL) with stirring. The resulting light yellow solution was placed in an oil bath at 55 °C and the mixture was stirred at that temperature overnight. Saturated brine (30 mL) was added and the mixture was extracted with CHCl3 (3×20 mL). The combined organic layer was dried over Na2SO4. Evaporation of the solvent gave 1 as a pale yellow oil (0.1935 g, 88 %). 1H NMR (CDCl3, 300 MHz, 56 oC) 10.23-10.15 (1H, br, NH), 6.57 (1H, s), 6.13 (2H, d, 6.0 Hz), 5.04 (1H, br, NH), 3.73 (2H, s), 3.41 (4H, s), 2.92 (2H, s), 2.76 (2H, t, 6.0 Hz), 2.24 (6H, s); 13C NMR (CDCl3, 75 MHz, 56 °C) 28.2, 30.6, 40.7, 44.6, 55.6, 97.9, 108.1, 109.1, 150.4, 152.1, 156.6; IR (neat) 3209, 2944, 2815, 2776, 1620, 1574, 1384, 1230, 1019, 761 cm-1; HRMS (ESI): calculated for C13H23O3N4S: [M+H]+ 315.1491: found 315.1497.

SEE NMR AT http://www.rsc.org/suppdata/gc/c1/c1gc15537g/c1gc15537g.pdf

Zantac (ranitidine) 300-mg tablet

 

 

PATENT

Patent EP0796256B1 - Process for preparing ranitidine - Google Patents

Google

Figure 00060001

HPLC

An Improved HPLC Method for the Determination of Ranitidine ...

Separation Science

An Improved HPLC Method for the Determination of Ranitidine Suitable for All Dosage Forms

PATENT

Patent WO2012082665A1 - Preparation of aminomethyl furans and ...

Google

Figure imgf000004_0001

 

CLIP

http://faculty.weber.edu/ewalker/Medicinal_Chemistry/topics/Antihistam_local_anesth/antihista.htm

CLIP

The paper was found in Green Chemistry,“Synthesis of ranitidine (Zantac) from cellulose-derived 5-(chloromethyl)furfural” by Mark Mescal et al, Green Chemistry,  2011,13, 3101-3102, DOI: 10.1039/c1gc15537g.  Once again, I am beating the press before they print so I supplied the Digital Object Identifier.  I am sure the sales for Ranitidine are quite large; who doesn’t get heartburn at one time or another.  I think it is very fortunate the author shows you can use a starting material that can be derived from just about any source of cellulose.  I find it interesting how renewable feedstocks can be utilized in industry and become part of important commodities, such as plastics, pharmaceuticals, etc.  This paper refers to another discussing where the starting material was derived from.  Starting material can be sugars, cellulose or raw cellulosic biomass and the reaction can produce yields of 80-90 %. M.Mascal and E. B. Nikitin, Angew. Chem., Int. Ed., 2008, 47, 7924;On with the show, though.  The original synthetic route was provided in the paper and I will provide it to you.

Furfural 1 was reduced to give the furfuryl alcohol 2.  The furfuryl alcohol is methylaminated to give 3, which is reacted with cysteamine in concentrated HCl to give 4.  This is condensed with 1-methylthio-1-methylamino-2-nitroethylene to give the final product.  The patent literature has the yield < 50 % for the aminomethylation and subsequent reaction with cysteamine, but recently, these steps have been reported to have higher conversions.

This new synthesis, apart from using a renewable feedstock as a starting material, has synthetic steps with an average yield of 91 %, and requires no chromatography.  Note that N-acetylcysteamine was used as opposed to cysteamine in the first step, in high yield.  A reductive amination with methylamine gives 8 again in high yield.  Treatment with KOH provides the free amine 9 and  the final step is the condensation with the nitroethylene used in the previous synthesis

Got heartburn ? Here is a synthesis to satisfy that appetite for good chemistry

Paper

Critical influence of 5-hydroxymethylfurfural aging and decomposition on the utility of biomass conversion in organic synthesis
Angewandte Chemie, International Edition (2016), 55, (29), 8338-8342

http://onlinelibrary.wiley.com/doi/10.1002/anie.201602883/abstract

http://onlinelibrary.wiley.com/store/10.1002/anie.201602883/asset/supinfo/anie201602883-sup-0001-misc_information.pdf?v=1&s=5b3f04dbb73a9be9c1d9c5350763b4e292d64f27

 

 

5-HMF. 1H NMR (400 MHz, DMSO-d6) δ = 9.54 (s, 1H, C(O)H), 7.49 (d, J = 3.5 Hz, 1H, CHfuran), 6.60 (d, J = 3.5 Hz, 1H, CH-furan), 5.57 (t, J = 5.9 Hz, 1H, OH), 4.51 (d, J = 5.9 Hz, 2H, CH2OH). 13C{1H} NMR (101 MHz, DMSO-d6) δ = 177.9 (C(O)H), 162.2, 151.7 (C-furan), 124.4, 109.7 (CH-furan), 55.9 (CH2OH). Anal. calcd. For C6H6O3 (126.11): C 57.14, H 4.80; found: C 57.08, H 4.79.

Abstract

Spectral studies revealed the presence of a specific arrangement of 5-hydroxymethylfurfural (5-HMF) molecules in solution as a result of a hydrogen–bonding network, and this arrangement readily facilitates the aging of 5-HMF. Deterioration of the quality of this platform chemical limits its practical applications, especially in synthesis/pharma areas. The model drug Ranitidine (Zantac®) was synthesized with only 15 % yield starting from 5-HMF which was isolated and stored as an oil after a biomass conversion process. In contrast, a much higher yield of 65 % was obtained by using 5-HMF isolated in crystalline state from an optimized biomass conversion process. The molecular mechanisms responsible for 5-HMF decomposition in solution were established by NMR and ESI-MS studies. A highly selective synthesis of a 5-HMF derivative from glucose was achieved using a protecting group at O(6) position.

 

PAPER

Phytochemical screening and investigation of antiulcer activity of Tridax procumbens
International Journal of Pharmacy and Technology (2015), 6, (4), 7679-7690

Lavanya Asula* , A. Sony John, Deepthi Kotturi, P. Srividyalaxmi, R. Soni and Y. Mamatha Kalyani Department of Pharmacy, Jawaharlal Nehru Technological University, Holy Mary Institute of Technology and Science College of Pharmacy Hyderabad, India. Email: lavanya.asula@gmail.com

 

PATENT

CN 104258704

Waste gas treatment and methyl mercaptan recovery process in production process of cimetidine and ranitidine

cimetidine and ranitidine terms widely used in the treatment of stomach is bound to promote the continuous mass production of APIs, however, the raw material in the manufacturing process of the drug inevitably produce methyl mercaptan, dimethyl sulfide, a methylamine, carbon disulfide and nitromethane workshop emissions. Because of methyl mercaptan, dimethyl sulfide into the atmosphere having foul odor. Resulting in the production shop around smelling, and even affect the normal life of residents of several kilometers around. So some manufacturers use incineration method expects to dispose of the waste gas combustion, which reduces air pollution to some extent. But using incineration method has two drawbacks: one gas methyl mercaptan, dimethyl sulfide gas combustion higher value produce a few meters of flames burning heat generated while it is easy to burn incinerator, security posed by the chemical production big risk; on the other hand by a combustion method can not solve the odor problem, air pollution is still grim, because incomplete combustion, odor difficult to eliminate people's sense of smell is particularly sensitive to the perception of mercaptans, while burning a large amount of sulfur dioxide in the same air pollution. There's manufacturers to adopt authoritarian incinerator burning after the first use of chlorine dioxide generator eliminate odor, although this method has a certain smell to eliminate the effect of improving, but requires authoritarian equipment, increasing the cost of gas treatment and discharge sulfur dioxide into the air is still there.

 

 

PATENT

CN 102408398

https://www.google.com/patents/CN102408398A?cl=en

 

Title: Ranitidine

CAS Registry Number: 66357-35-5

CAS Name: N-[2-[[[-5-[(Dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N¢-methyl-2-nitro-1,1-ethenediamine

Molecular Formula: C13H22N4O3S

Molecular Weight: 314.40

Percent Composition: C 49.66%, H 7.05%, N 17.82%, O 15.27%, S 10.20%

Literature References: Histamine H2-receptor antagonist which inhibits gastric acid secretion. Prepn: B. J. Price et al., FR2384765; eidem, US 4128658 (both 1978 to Allen & Hanburys). HPLC determn in plasma: P. F. Carey, L. E. Martin, J. Liq. Chromatogr. 1979, 1291. Pharmacological studies: J. Bradshaw et al., Br. J. Pharmacol. 66, 464 (1979); M. J. Daly et al., Gut 21,408 (1980). Efficacy in treatment of duodenal ulcers: A. Berstad et al., Scand. J. Gastroenterol. 15, 637 (1980); R. P. Walt et al.,Gut 22, 49 (1981). Review of pharmacology and therapeutic use: R. N. Brogden et al., Drugs 24, 267-303 (1982). Comprehensive description: M. Hohnjec et al., Anal. Profiles Drug Subs. 15, 533-561 (1986).

Properties: Solid, mp 69-70°.

Melting point: mp 69-70°

 

Derivative Type: Hydrochloride

CAS Registry Number: 66357-59-3

Manufacturers' Codes: AH-19065

Trademarks: Azantac (GSK); Melfax (Apotex); Noctone (GEA); Raniben (Firma); Ranidil (Menarini); Raniplex (Fournier); Sostril (Cascan); Taural (Roemmers); Terposen (Vir); Trigger (Polifarma); Ulcex (Guidotti); Ultidine (GSK); Zantac (GSK); Zantic (GSK)

Molecular Formula: C13H22N4O3S.HCl

Molecular Weight: 350.86

Percent Composition: C 44.50%, H 6.61%, N 15.97%, O 13.68%, S 9.14%, Cl 10.10%

Properties: Off-white solid, mp 133-134°. Freely sol in acetic acid and water, sol in methanol, sparingly sol in ethanol. Practically insol in chloroform.

Melting point: mp 133-134°

 

Derivative Type: Bismuth citrate

CAS Registry Number: 128345-62-0

Additional Names: Ranitidine bismutrex

Manufacturers' Codes: GR-122311X

Trademarks: Pylorid (GSK); Tritec (GSK)

Molecular Formula: C13H22N4O3S.C6H5BiO7

Molecular Weight: 712.48

Percent Composition: C 32.03%, H 3.82%, N 7.86%, O 22.46%, S 4.50%, Bi 29.33%

Literature References: Pharmacology and activity vs Helicobacter sp: R. Stables et al., Aliment. Pharmacol. Ther. 7, 237 (1993).

 

Therap-Cat: Antiulcerative.

Keywords: Antiulcerative; Histamine H2-Receptor Antagonist.

References

1. ^ Jump up to:a b c d e f g "Ranitidine". The American Society of Health-System Pharmacists. Retrieved Dec 1, 2015.
2. Jump up^ Fedorowicz, Z; van Zuuren, EJ; Hu, N (14 March 2012). "Histamine H2-receptor antagonists for urticaria.". The Cochrane database of systematic reviews. 3: CD008596.doi:10.1002/14651858.CD008596.pub2. PMID 22419335.
3. Jump up^ Tleyjeh, IM; Abdulhak, AB; Riaz, M; Garbati, MA; Al-Tannir, M; Alasmari, FA; Alghamdi, M; Khan, AR; Erwin, PJ; Sutton, AJ; Baddour, LM (2013). "The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.". PLOS ONE. 8 (3): e56498. doi:10.1371/journal.pone.0056498.PMC 3587620. PMID 23469173.
4. Jump up^ Fischer, Janos (2010). Analogue-based Drug Discovery II. John Wiley & Sons. p. 4.ISBN 9783527632121.
5. Jump up^ Hara, Takuji (2003). Innovation in the pharmaceutical industry the process of drug discovery and development. Cheltenham, U.K.: Edward Elgar. p. 94.ISBN 9781843765660.
6. Jump up^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

Ranitidine

Systematic (IUPAC) name
N-(2-[(5-[(dimethylamino)methyl]furan-2-yl)methylthio]ethyl)-N'-methyl-2-nitroethene-1,1-diamine
Clinical data
Pronunciation	/rəˈnɪtᵻdiːn/
Trade names	Zantac, others
AHFS/Drugs.com	Monograph
MedlinePlus	a601106
License data	US FDA: Ranitidine
Pregnancy category	AU: B1 US: B (No risk in non-human studies)
Routes of administration	Oral, IV
Legal status
Legal status	AU: S2 (Pharmacy only) UK: General sales list (GSL, OTC) US: OTC/RX
Pharmacokinetic data
Bioavailability	39 to 88%
Protein binding	15%
Metabolism	Hepatic: FMOs, including FMO3; other enzymes
Biological half-life	2–3 hours
Excretion	30–70% Renal
Identifiers
CAS Number	66357-35-5
ATC code	A02BA02 (WHO) A02BA07 (WHO) (ranitidine bismuth citrate)
PubChem	CID 3001055
IUPHAR/BPS	1234
DrugBank	DB00863
ChemSpider	4863
UNII	884KT10YB7
KEGG	D00422
ChEBI	CHEBI:8776
ChEMBL	CHEMBL1790041
Synonyms	Dimethyl [(5-{[(2-{[1-(methylamino)- 2-nitroethenyl]amino}ethyl)sulfanyl] methyl}furan-2-yl)methyl]amine
Chemical data
Formula	C13H22N4O3S
Molar mass	314.4 g/mol

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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(%).

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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

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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)

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