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17th April 2019 @ 10:15

2-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine was synthesised from the previously synthesised 2-chloro-6-(2-hydrazinyl)(4-chlorobenzylidene)pyrazine intermediate.

Reaction Scheme

Reaction 2 scheme.png

Risk assessment

4chlorobenzaldehyde reaction 2 risk assessment.pdf

Reagents

                                                                                     mass/g      moles/mmol       equivalents

2-chloro-6-(2-hydrazinyl)(4-chlorobenzylidene)pyrazine       0.0201       0.062                   1.0

diacetoxyiodobenzene                                                            0.0310       0.096                   1.5

Proceedure

A round bottomed flask was charged with Synthesis of 2-Chloro-6-(2-hydrazinyl)(4-chlorobenzylidene)pyrazine (0.0212 g, 0.067 mmol), diacetoxyiodobenzene (0.0250 g, 0.078 mmol) and dichloromethane (10 mL) in. The resulting solution was stirred at room temperature and monitored using TLC (7: 3 ethyl acetate: light petroleum ether solvent used) until completion. The resulting product was then isolated by column chromatography, using the same solvents (Rf = 0.4) and dried via vacuum filtration yielding a white powder (0.0181g, 85.7%). The product was characterised via 1H and 13C NMR, infrared and melting point analysis.

Analytical Data

4chlorobenzaldehyde reaction2 H NMR spectrum.pdf

4chlorobenzaldehyde reaction2 IR spectrum.pdf

4chlorobenzaldehyde reaction2 Mass spectrum.pdf

4chlorobenzaldehyde reaction2 C NMR spectrum.pdf

Mpt = 261-265C

Inchi keys

2-chloro-6-(2-hydrazinyl)(4-chlorobenzylidene)pyrazine IREXIIXDQDGVMX-UHFFFAOYSA-N

diacetoxyiodobenzene  ZBIKORITPGTTGI-UHFFFAOYSA-N

2-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine VCWFDFYRPOTNNX-UHFFFAOYSA-N

Attached Files
17th April 2019 @ 09:42

2-chloro-6-(2-hydrazinyl)(4-chlorobenzylidene)pyrazine was synthesised from 2-chloro-6-hydrazinopyrazine and 4-chlorobenzaldehyde, as an intermediate in the synthesis of 2-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine

Reaction scheme

Reaction 1 scheme.png

Risk Assessment

4chlorobenzaldehyde reaction1 risk assessment.pdf

Reagents

                                                     mass/g           moles/mmol         equivalents

2-chloro-6-hydrazinopyrazine           0.049              0.339                   1.0

4-chlorobenzaldehyde                      0.056             0.364                    1.1

Proceedure

A round bottomed flask was charged with 2-chloro-6-hydrazinopyrazine (0.0490 g, 0.339 mmol), 4-chlorobenzaldehyde (0.0560 g, 0.399 mmol) and ethanol (20 mL) in. The resulting solution was heated under reflux and monitored using TLC (3: 7 ethyl acetate: light petroleum ether solvent used) until completion (Rf = 0.35). The resulting product was then isolated and dried via vacuum filtration yielding a light yellow powder (0.0436g, 44.5%). The product was characterised via 1H and 13C NMR, infrared and melting point analysis. 

Analytical data

4chlorobenzaldehyde reaction1 C NMR spectrum.pdf

4chlorobenzaldehyde reaction1 Mass spectrum.pdf

4chlorobenzaldehyde reaction1 H NMR spectrum.pdf

Mpt = 215 - 225C

InChl Key

2-chloro-6-hydrazinopyrazine  FEDQSVIJHNBUHH-UHFFFAOYSA-N

4-chlorobenzaldehyde  AVPYQKSLYISFPO-UHFFFAOYSA-N

2-chloro-6-(2-hydrazinyl)(4-chlorobenzylidene)pyrazine  IREXIIXDQDGVMX-UHFFFAOYSA-N

Attached Files
16th April 2019 @ 21:52

5-chloro-3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyrazine was synthesised using previously synthesised intermediate 2-chloro-6-(2-hydrazinyl)(2-hydroxybenzylidene)pyrazine.

Reagent Mass/g Moles/mmol Equivalents
2-chloro-6-(2-hydrazinyl)(2-hydroxybenzylidene)pyrazine 0.020 0.080 1.00
diacetoxyiodobenzene 0.0290 0.090 1.13

Yield: 54.3%

Procedure

2-chloro-6-(2-hydrazinyl(2-hydroxybenzylidene)pyrazine (20 mg, 0.080 mmol, 1 eq.) and diacetoxyiodobenzene (29 mg, 0.090 mmol, 1.13 eq.) was dissolved in DCM (10 mL) and left overnight stirring under an atmosphere of nitrogen. The reaction was monitored by TLC using a variety of solvent systems (1:1 PET ether: EtOAc, 1:3 PET ether: EtOAc, 100% EtOAc, 20% MeOH in EtOAc and 1% acetic acid in EtOAc) however the spots did not move off the baseline and so the product was not suitable for purification by column chromatography. The solvent was removed in vacuoto give a dark orange powder which was analysed by mass spec and 1H NMR. Both NMR and mass spec showed that the intended product was not formed.

Analytical Data 

mp 261-264 °C.

InChI Key:

2-chloro-6-(2-hydrazinyl(2-hydroxybenzylidene)pyrazine: BTVQPPGRWZUSCA-LHHJGKSTSA-N

PIDA: ZBIKORITPGTTGI-UHFFFAOYSA-N

5-chloro-3-(2-hydroxyyphenyl)-[1,2,4]triazolo[4,3-a]pyrazine: GLKVTIUQXSULMV-UHFFFAOYSA-N

 

Attached Files
16th April 2019 @ 20:58

2-chloro-6-(2-hydrazinyl)(2-hydroxybenzylidene)pyrazine was synthesised as an intermediate compound in the overall synthesis of 5-chloro-3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyrazine.

Reagent Mass/g Moles/mmol Equivalents
2-chloro-6-hydrazinopyrazine  0.0523 0.360 1.00
4-carboxybenzaldehyde 0.0560 0.460 1.28

Yield: 86.1%

Procedure

2-chloro-6-hydrazinopyrazine (52.3 mg, 0.36 mmol, 1.0 eq.) and 2-hydroxybenzaldehyde (56.0 mg, 0.46 mmol, 1.28 eq.) were added to a round-bottom flask and dissolved in ethanol (10 mL). The resulting solution was heated to 80 °C under reflux for 75 minutes. The reaction was monitored using TLC with a solvent system of 7: 3 PET ether: EtOAc. Once the reaction had gone to completion, the solution was recrystallised. The minimum amount of boiling water needed to precipitate out the product was added, and the mixture was then cooled to allow the product to crash out. The crystals were filtered under vacuum to give a light-yellow powder. The product was analysed by mass spec, IR, 1H and 13C NMR.

Analytical Data 

mp 228 – 231 °C (from EtOH); RF0.44; nmax/cm-13157 (NH), 1625 (CN), 1563 (NH), 1417 (OH); dH (300 MHz, DMSO-d6): d11.52 (s, 1H, NH), 10.22 (s, 1H, OH), 8.44 (s, 1H, pyrazine C), 8.37 (s, 1H, pyrazine C), 8.03 (s, 1H, N=CH) 7.75-7.72 (d, 1H, J= 9.0 Hz, Ar), 7.25-7.20 (t, 1H, J= 9.0 Hz, Ar), 6.91-6.87 (m, 2H, Ar); dC (75 MHz, DMSO-d6): d156.4 (pyrazine C), 152.3 (pyrazine C), 145.9 (C=N), 141.2 (COH), 132.4 (CCl), 130.9, 129.0 (Ar), 126.9 (Ar), 120.5 (Ar), 119.7 (Ar), 116.4 (Ar); m/z 249.0538 (M+H+).

InChI Key:

2-chloro-6-hydrazinopydrazine: FEDQSVIJHNBUHH-UHFFFAOYSA-N

2-hydroxybenzaldehyde: SMQUZDBALVYZAC-UHFFFAOYSA-N

2-chloro-6-(2-hydrazinyl)(2-hydroxybenzlidene)pyrazine: BTVQPPGRWZUSCA-LHHJGKSTSA-N

Attached Files
16th April 2019 @ 15:52
Reagent Mass/g Moles/mmol Equivalents
diacetoxyiodobenzene  0.023 0.0714 0.9
2-chloro-6-(2-hydrazinyl(4-carboxybenzylidene))pyrazine 0.022 0.0795 1.0

Yield: 40%

Procedure

PIDA (0.023 g, 0.0714 mmol, 0.9 eq.) was added to a stirred solution of the intermediate pyrazine I1 (0.022 g, 0.0795 mmol, 1 eq.) and DCM (10 mL, 0.157 mol, 2 eq.) at rt under N. The resulting mixture was stirred at rt for 150 min. Then, the solvent was evaporated under reduced pressure to give the crude product. Purification by flash column chromatography on silica with 80:19:1 EtOAc-PET ether-Acetic acid as eluent gave P1 (0.0087 g, 40%) as a light yellow powder

Analytical Data 

mp 269 – 274 °C; RF (80:19:1 EtOAc-PET ether-Acetic acid) 0.26; 1H NMR (300 MHz, CDCl3) 𝛿# 9.31 (s, 1H), 8.19-8.16 (d, J = 9.0 Hz, 2H), 7.85 (s, 1H), 7.71-7.68 (d, J = 9.0 Hz, 2H), 3.42 (s, 1H); MS (ESI) m/z calculated for C12H8ClN4O2 (M + H)+ 275.0329, found 275.0330 (0.4 ppm error)

1H NMR spectrum (300 MHz) of 5-chloro-3-(4-carboxyphenyl)-[1,2,4]triazolo[4,3- a]pyrazine P1in CDCl3.

ESI Mass spectrum of 5-chloro-3-(4-carboxyphenyl)-[1,2,4]triazolo[4,3-a]pyrazine P1.

Risk Assessment 

Risk Assessment

Reaction Scheme

Reaction Scheme
Attached Files