Copper-catalyzed pyrrole synthesis from 3,6-dihydro-1,2-oxazines

Copper-catalyzed pyrrole synthesis from 3,6-dihydro-1,2-oxazines

 

Naoki Yasukawa,^a  Marina Kuwata,^a  Takuya Imai,^a  Yasunari Monguchi,^a  Hironao Sajiki*^a  and Yoshinari Sawama*^a 

 Author affiliations

*Corresponding authors

^aLaboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
E-mail: sajiki@gifu-pu.ac.jp, sawama@gifu-pu.ac.jp
Fax: +81-58-230-8109

Abstract

Highly-functionalized pyrroles could be effectively synthesized from 3,6-dihydro-1,2-oxazines using a heterogeneous copper on carbon (Cu/C) under neat heating conditions. Furthermore, the in situ formation of 3,6-dihydro-1,2-oxazines via the hetero Diels–Alder reaction between nitroso dienophiles and 1,3-dienes and the following Cu/C-catalyzed pyrrole synthesis also provided the corresponding pyrrole derivatives in a one-pot manner.

Brown solid; M. p. 107–108 o C;
IR (ATR) cm-1 : 3064, 2923, 2851, 1687, 1596, 1562, 1541, 1498, 1488, 1459, 1451, 1422, 1390, 1343, 1319, 1256, 1187, 1098, 1073, 1053, 1037, 1009;
1 H NMR (500 MHz, CDCl3): δ 7.37–7.28 (m, 5H), 7.17 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.95 (dd, J = 2.0, 3.0 Hz, 1H), 6.45 (dd, J = 2.0, 3.0 Hz, 1H), 6.37 (dd, J = 3.0, 3.0 Hz, 1H);
13C NMR (125 MHz, CDCl3): δ 140.19, 132.52, 131.85, 131.19, 129.65, 129.14, 126.84, 125.69, 124.83, 120.24, 110.97, 109.38;
ESI-HRMS m/z: 298.0231([M+H+ ]); Calcd for C16H13NBr: 298.0226.
 

//////////3,6-dihydro-1,2-oxazines

4,4,5,5-tetramethyl-2-phenethyl-1,3,2-dioxaborolane

http://orgsyn.org/demo.aspx?prep=v94p0234

 4,4,5,5-Tetramethyl-2-phenethyl-1,3,2-dioxaborolane (1) has the following physical and spectroscopic properties: R_f = 0.47 (3:97, ethyl acetate:pentane), the checkers report the following values for 1: R_f = 0.09 (3:97 ethyl acetate:pentane); R_f = 0.52 (10% EtOAc in hexanes); Merck silica gel 60 F254 plate; mp 38-39 °C; 

¹H NMR pdf(CDCl₃, 400 MHz) δ: 1.18 (t, J = 8.4 Hz, 2H), 1.26 (s, 12H), 2.79 (t, J = 8.0 Hz, 2H), 7.16-7.22 (m, 1H), 7.23-7.32 (m, 4H); 

¹³C NMR pdf(CDCl₃, 151 MHz) d: 25.0, 30.1, 83.2, 125.6, 128.1, 128.3, 144.6 [N.B. the carbon attached to boron was not observed due to quadrupolar relaxation]; 

HRMS (ESI⁺) calculated for C₁₄H₂₂BO₂⁺ = 233.1707, mass found = 233.1710; 

IR (film): 3026, 2978, 2929, 1372, 1318, 1139, 848, 755, 703 cm^-1; 

Anal. calcd for C₁₄H₂₁BO₂: C, 72.44; H, 9.12. Found: C, 72.18; H, 9.28. 

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3.4. 1,2,3,4-Tetra-O-Acetyl-β-d-Mannuronic Acid

Laura Beswick

2nd degree connection

PhD Student at Keele University

Gavin J. Miller

2nd degree connection

Lecturer in Organic Chemistry at Keele University

3.4. 1,2,3,4-Tetra-O-Acetyl-β-d-Mannuronic Acid (4)

To a vigorously stirred solution of 1,2,3,4-tetra-O-acetyl-β-d-mannopyranose (3) (1.5 g, 4.30 mmol, 1.0 equiv.) in dichloromethane (20 mL) and water (10 mL) was added (2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical (TEMPO) (336 mg, 2.2 mmol, 0.50 equiv.) and [bis(acetoxy)iodo]benzene (BAIB) (6.9 g, 21.5 mmol, 5.00 equiv.). The solution was stirred at RT for 5 h, whereupon TLC analysis (hexane/ethyl acetate, 1/1) showed complete conversion of starting material to a baseline Rf value spot. The reaction was quenched with aqueous Na2S2O3 solution (10% w/v, 30 mL), the organic layer removed and the aqueous layer acidified to pH 3 using 1M HCl, followed by extraction with ethyl acetate (2 × 30 mL). The organic extracts were combined, dried (MgSO4), filtered and concentrated in vacuo to afford 1,2,3,4-tetra-O-acetyl-β-d-mannuronic acid (4) as a white solid (1.2 g, 3.3 mmol, 75%). Rf = 0.81 (dichloromethane/methanol, 9/1);

 1H-NMR (300 MHz, CDCl3) δH5.96 (1H, d, J = 1.5 Hz, H1), 5.50 (1H, dd, J = 3.2, 1.5 Hz, H2), 5.48 (1H, appt, J = 9.1 Hz, H4), 5.21 (1H, dd, J = 9.1, 3.2 Hz, H3), 4.2 (1H, d, J = 9.1 Hz, H5), 2.21 (3H, s, C(O)CH3), 2.13 (3H, s, C(O)CH3), 2.10 (3H, s, C(O)CH3), 2.04 (3H, s, C(O)CH3).

 13C-NMR (100 MHz, CDCl3) δC 169.9 (C=O), 169.7 (C=O), 169.5 (C=O), 169.4 (C=O), 168.2 (C=O), 89.4 (C1), 72.3 (C5), 69.3 (C3), 66.9 (C2), 65.9 (C4), 20.4 (C(O)CH3), 20.4 (C(O)CH3), 20.3 (C(O)CH3), 20.2 (C(O)CH3); 

FT-HRMS NSI (ES−) m/z Found: (M−H)− 361.0767, C14H17O11 requires 361.0776; FT-IR vmax/cm−1 2986 (O–H), 1751 (C=O).

Molbank 2017, 2017(3), M947; doi:10.3390/M947

Communication

1,2,3,4-Tetra-O-Acetyl-β-d-Mannuronic Acid

Laura Beswick and Gavin J. Miller *

Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK

*

Correspondence: Tel.: +44-1782-734442

Received: 3 July 2017 / Accepted: 11 July 2017 / Published: 14 July 2017

Abstract

: 

1,2,3,4-Tetra-O-acetyl-β-d-mannuronic acid was synthesized in three steps from commercial d-mannose in 21% yield. Regioselective 6-O-tritylation followed by per-acetylation and 6-OTr removal using HBr/AcOH gave the required primary alcohol substrate, which was then oxidised to the target compound using TEMPO/BAIB. None of the synthetic steps required column chromatography and the product was fully characterized by 1H-NMR, 13C-NMR, 2D NMR, MS and IR.

http://www.mdpi.com/1422-8599/2017/3/M947/htm

Keele University, Keele, Staffordshire

Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University,

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“ORGANIC SPECTROSCOPY INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

(4-(3-(methylsulfinyl)phenyl)-l-propyl-l,2,3,6- tetrahydropyridine)

Example 7 - Preparation Of Compound 7 (4-(3-(methylsulfinyl)phenyl)-l-propyl-l,2,3,6- tetrahydropyridine)

4-(3-(methylsulfinyl)phenyl)-1-propyl- 1 ,2,3,6-tetrahydropyridin-1-ium chloride Sulfuric acid (42.23g, 0.43 lmol, leq) was added to a mixture of 4-hydroxy-4-(3- (methylsulfonyl)phenyl)-l-propylpiperidin-l-ium chloride (130g, 0.431 mo, leq) and toluene (650mL) at room temperature. The resulting two-phase solution was refluxed for lhour and HPLC showed that the product reached 95% area. The reaction mixture was cooled down to 20°C and the toluene phase was decanted to give viscous residue that was diluted with water (600mL) and neutralized with 2N NaOH to pH~4.2. Hydrogen peroxide (50%, 32.21g, 0.474mol, l.leq) was added dropwise to the water phase and the mixture was stirred at 60°C for lh after which the product reached 96% area (HPLC).

Toluene (600mL) was added to the reaction mixture and made basic first with 25% NaOH (60g) and finally with 10% NaOH up to pH 12. The phases were separated and the water phase was re-extracted with toluene (2xl00mL). The combined toluene phases were washed with 5% sodium sulfite (150mL), brine (150mL) and water (150mL). The toluene phase was then concentrated under vacuum on a rotavapor to give 111.3g oil (HPLC area: 96.6%). Methanol (50mL) was added to the residue and it was filtered and cooled down on ice batch. Dry HC1 in ethyl acetate was added up to pH 1-2 (120mL) and lOOmL of ethyl ether were added to give two phases mixture. The mixture was seeded with the product and precipitation started. The reaction mixture was stirred on ice bath (2-5°C) for additional lh, filtered and washed with 1/3 ethyl acetate/ether mixture (lOOmL) to give 140g of very hygroscopic light yellow solid that was dried on a rotavapor for 2h and stored under nitrogen in deep freeze. The dry 4-(3-(methylsulfinyl)phenyl)-l-propyl-l,2,3,6-tetrahydropyridine-HCl is slightly yellowish solid (94.1g, 79% yield, HPLC (254nm): 96.3% area, 1H-NMR assay: 97.5%).

NMR Identity Analysis of Compound 7

Compound 7: 

The following data in Tables 14 and 15 was determined using a sample of Compound 7, a solvent of CDCb, and the instruments were a Bruker AMX500 and Avance III 800 MHz instrument.

Table 14: Assignment of ¾ NMR"

"Spectra is calibrated by the solvent residual peak (2.5 ppm).

bafter addition of small amount of CeDe

Table 15: Assignment of 13C NMRa*

a Spectra is calibrated by a solvent peak (77.0 ppm)

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016003919&recNum=5&docAn=US2015038349&queryString=EN_ALL:nmr%20AND%20PA:(teva%20pharmaceutical)&maxRec=677#H3

3,6−bis([1,1'−biphenyl]−4−ylmethyl)−1,2,4,5−tetrazine

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).

 

(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

3,6−bis([1,1'−biphenyl]−4−ylmethyl)−1,2,4,5−tetra zine

3,6−bis([1,1'−biphenyl]−4−ylmethyl)−1,2,4,5−tetra zine

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.

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 tetrazines from gem-difluoroalkenes under aerobic conditions at room temperature

Zheng Fang,^a   Wen-Li Hu,^a   De-Yong Liu,^a  Chu-Yi Yu^ab and   Xiang-Guo Hu*^a  

Hide Affiliations

*

Corresponding authors

^a

National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, P. R. China
 E-mail: huxiangg@iccas.ac.cn

^b

Beijing 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

3,6−bis([1,1'−biphenyl]−4−ylmethyl)−1,2,4,5−tetra zine (3a). (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.



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