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Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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CAS No. : | 28989-23-3 | MDL No. : | MFCD00046083 |
Formula : | C10H5ClN2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 220.68 | Pubchem ID : | - |
Synonyms : |
|
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P310-P330-P361-P403+P233-P405-P501 | UN#: | 2811 |
Hazard Statements: | H301-H311-H331 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium nitrite In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
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92% | for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.4% | With pyridine; disulfur dichloride at 140℃; for 16h; | 55 [0739] to a mixture of compound 96a (17.50 g, 113.51 mmol) and chlorosulfanyl thiohypochlorite (70.00 g, 518.36 mmol, 41.42 ml) was added pyridine (900.00 mg, 11.38 mmol). Then the reaction was stirred at 140°c for 16h. The reaction mixture was cooled to room temperature and quenched with ice/H2O (200 ml) and EtOAc (500 ml), yellow solid was was precipitate out, filtered and the filtrate was extracted with EtOAc(100 ml x 2), the combined organic was washed with brine (100 ml), dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by flash silica gel chromatography (isco; 120 g sepaflash silica flash column, eluent of 0 ~ 10% ethyl acetate/petroleum ether gradient 50 ml/min) to give compound 96b (21.00 g, 70.4% yield) as light yellow solid. 1H NMR (400mhz, chloroform-d) δ 7.77 (br d, 7=7.1 hz, 2h), 7.65 - 7.53 (m, 3h). |
33% | With pyridine; disulfur dichloride In water at 145℃; for 12h; | 127.2 Step 2: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile Step 2: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile Into a 50-mL round-bottom flask, was placed 2-(phenylmethylidene)propanedinitrile (1.5 g, 9.24 mmol, 1.00 equiv, 95%), S2Cl2 (5.3 g, 39.26 mmol, 4.00 equiv), pyridine (76.9 mg, 0.97 mmol, 0.10 equiv). The resulting solution was stirred for 12 h at 145° C. in an oil bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was extracted with 3*20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 700 mg (33%) of 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile as a yellow solid. |
33% | With pyridine; disulfur dichloride at 145℃; for 12h; | 127.2 Step 2: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile Into a 50-mL round-bottom flask, was placed 2-(phenylmethylidene)propanedinitrile (1.5 g, 9.24 mmol, 1.00 equiv, 95%), S2Cl2 (5.3 g, 39.26 mmol, 4.00 equiv), pyridine (76.9 mg, 0.97 mmol, 0.10 equiv). The resulting solution was stirred for 12 h at 145° C. in an oil bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was extracted with 3*20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 700 mg (33%) of 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile as a yellow solid. |
33% | With pyridine; disulfur dichloride at 145℃; for 12h; | 127.2 Step 2; 3-chloro-5-phenyl-l,2-thiazole-4-carbonitrile Into a 50-mL round-bottom flask, was placed 2- (phenylmethylidene)propanedinitrile (1.5 g, 9.24 mmol, 1.00 equiv, 95%), S2CI2 (5.3 g, 39.26 mmol, 4.00 equiv), pyridine (76.9 mg, 0.97 mmol, 0.10 equiv). The resulting solution was stirred for 12 h at 145°C in an oil bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was extracted with 3x20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 10). This resulted in 700 mg (33%) of 3-chloro-5- phenyl-l,2-thiazole-4-carbonitrile as a yellow solid. |
With pyridine; disulfur dichloride at 140 - 150℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium sulfide In methanol; water for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium sulfide 1.) MeOH, H2O, reflux, 3 h, 2.) Et2O, H2O, 12 h; Yield given; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium sulfide 1.) MeOH, H2O, reflux, 3 h, 2.) Et2O, H2O, 12 h; Yield given; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium sulfide 1.) MeOH, H2O, reflux, 3 h, 2.) Et2O, H2O, 12 h; Yield given; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile With sodium sulfide In methanol; water for 3h; Heating; Stage #2: methyl iodide In water at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With 18-crown-6 ether; potassium carbonate In toluene at 110℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium fluoride; 18-crown-6 ether In toluene at 110℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium fluoride; 18-crown-6 ether In toluene at 110℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium fluoride; 18-crown-6 ether In toluene at 110℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sulfuric acid at 20 - 100℃; for 2.66667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 100 percent / Pd(OAc)2 / dimethylformamide / 0.25 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 100 percent / Pd(OAc)2 / dimethylformamide / 0.25 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 85 percent / POBr3 / 24 h / 100 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 85 percent / POBr3 / 24 h / 100 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 85 percent / POBr3 / 24 h / 100 °C |
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 85 percent / POBr3 / 24 h / 100 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 85 percent / POBr3 / 24 h / 100 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 85 percent / POBr3 / 24 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 71 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 71 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 71 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C |
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 71 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 71 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 71 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 29 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 29 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 29 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C |
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 29 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 29 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 29 percent / triethylamine / CH2Cl2 / 0.5 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C | ||
Multi-step reaction with 5 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C | ||
Multi-step reaction with 5 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile With sulfuric acid at 135℃; for 3h; Stage #2: With sodium nitrite In water at 0 - 50℃; for 0.5h; | 127.3 Step 3: 3-chloro-5-phenyl-1,2-thiazole-4-carboxylic acid Step 3: 3-chloro-5-phenyl-1,2-thiazole-4-carboxylic acid Into a 50-mL round-bottom flask, was placed 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile (700 mg, 3.01 mmol, 1.00 equiv, 95%), con.H2SO4 (4 mL). The resulting solution was stirred for 3 hr at 135° C. in an oil bath. This was followed by the addition of a solution of NaNO2 (318 mg, 4.61 mmol, 1.45 equiv) in water (15 mL) dropwise with stirring at 0° C. The resulting solution was allowed to react, with stirring, for an additional 0.5 h while the temperature was maintained at 50° C. in an oil bath. The resulting solution was extracted with 3*20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2*50 mL of sodium hydroxide/H2O(10%). The resulting solution was extracted with 3*100 mL of ethyl acetate. The aqueous phase was adjusted to 3 with 2N HCl. The resulting solution was extracted with 3*100 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. This resulted in 500 mg (66%) of 3-chloro-5-phenyl-1,2-thiazole-4-carboxylic acid as a white solid. |
66% | Stage #1: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile With sulfuric acid at 135℃; for 3h; Stage #2: With water; sodium nitrite at 0 - 50℃; for 15h; | 127.3 Step 3: 3-chloro-5-phenyl-1,2-thiazole-4-carboxylic acid Into a 50-mL round-bottom flask, was placed 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile (700 mg, 3.01 mmol, 1.00 equiv, 95%), con.H2SO4 (4 mL). The resulting solution was stirred for 3 hr at 135° C. in an oil bath. This was followed by the addition of a solution of NaNO2 (318 mg, 4.61 mmol, 1.45 equiv) in water (15 mL) dropwise with stirring at 0° C. The resulting solution was allowed to react, with stirring, for an additional 0.5 h while the temperature was maintained at 50° C. in an oil bath. The resulting solution was extracted with 3*20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2*50 mL of sodium hydroxide/H2O(10%). The resulting solution was extracted with 3*100 mL of ethyl acetate. The aqueous phase was adjusted to 3 with 2N HCl. The resulting solution was extracted with 3*100 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. This resulted in 500 mg (66%) of 3-chloro-5-phenyl-1,2-thiazole-4-carboxylic acid as a white solid. |
66% | Stage #1: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile With sulfuric acid at 135℃; for 3h; Stage #2: With sodium nitrite In water at 0 - 50℃; for 0.5h; | 127.3 Step 3; 3-chloro-5-phenyl-l,2-thiazole-4-carboxylic acid Into a 50-mL round-bottom flask, was placed 3 -chloro-5 -phenyl- 1 ,2-thiazole-4- carbonitrile (700 mg, 3.01 mmol, 1.00 equiv, 95%), con.H2S04 (4 mL). The resulting solution was stirred for 3 hr at 135°C in an oil bath. This was followed by the addition of a solution of NaN02 (318 mg, 4.61 mmol, 1.45 equiv) in water(15 mL) dropwise with stirring at 0°C. The resulting solution was allowed to react, with stirring, for an additional 0.5 h while the temperature was maintained at 50°C in an oil bath. The resulting solution was extracted with 3x20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x50 mL of sodium hydroxide/H2O(10%). The resulting solution was extracted with 3x100 mL of ethyl acetate. The aqueous phase was adjusted to 3 with 2N HC1. The resulting solution was extracted with 3x100 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. This resulted in 500 mg (66%) of 3 -chloro-5 -phenyl- 1,2- thiazole-4-carboxylic acid as a white solid. |
49.13% | Stage #1: 3-chloro-5-phenyl-1,2-thiazole-4-carbonitrile With sulfuric acid at 135℃; for 1h; Stage #2: With sodium nitrite In water at 0 - 50℃; for 0.5h; | 113 [1110] to a 100 ml round-bottom placed compound 96b (2.00 g, 9.06 mmol) was added H2SO4 (27.60 g, 281.40 mmol) dropwise, and stirred at 135 °C for lh. Then, the mixture was added NaNO2 (907 mg, 13.14 mmol) in H2O (10 ml) dropwise at 0 °C. The resulting solution was stirred at 50 °C for 0.5h. The reaction mixture was diluted with H2O (50 ml) and extracted with ethyl acetate (50 ml x 3). The combined organic layers were extracted with 10% NaOH (50 ml x 2). The aqueous phase was adjusted to 3 with in HCl, extracted with ethyl acetate (50 ml x 3). The combined organic layers were washed with brines (50 ml), dried Na2SO4, filtered and concentrated under reduced pressure to give a compound 213f (1.17 g, yield: 49.13%) as a yellow solid. 1H NMR (400mhz, DMSO-d6) δ 7.55 (d, 7=1.3 hz, 5h). MS (ESI) m/z (m +h)+ 239.9. |
Multi-step reaction with 2 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 88 percent / conc. H2SO4; sodium nitrite / 2.5 h / 20 - 100 °C | ||
1.7 g (71%) | With hydrogenchloride; sulfuric acid; sodium nitrite In water | 1 Preparation of 3-chloro-5-phenyl-4-isothiazolecarboxylic acid EXAMPLE 1 Preparation of 3-chloro-5-phenyl-4-isothiazolecarboxylic acid A mixture of 2.20 g (10 mole) of 3-chloro-5-phenyl-4-isothiazolecarbonitrile and 10 ml of concentrated sulfuric acid was heated at 130°-140° for 3 hours and cooled with an ice bath. A solution of 1.0 g (14.5 mole) of sodium nitrite in 5 ml of water was added dropwise. The addition of sodium nitrite solution was adjusted so that the temperature did not exceed 30°. After complete addition of the sodium nitrite solution, the mixture was poured into 200 ml of water, and the mixture was heated at 50° for 1/2 hour and cooled. The aqueous solution was extracted with ether (24.50 ml). The ether extract was extracted with 50 ml of 10% sodium hydroxide (2 times). The extract was made acidic with 50 ml of concentrated HCl (a precipitate formed) and was extracted twice with 50 ml of ether. The ether solution was dried (MgSO4) and concentrated to give 1.8 g (75%) of tan needles, mp 166.5°-168°, which was recrystallized from hexane: ether to give 1.7 g (71%) of the desired product as yellow needles. mp 167°-169°. Anal. Calc'd for C10 H6 ClNO2 S: C, 50.11; H, 2.82; N, 5.85; Cl, 14.9 Found: C, 50.19; H, 2.53; N, 5.88; Cl, 14.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C | ||
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C | ||
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 85 percent / POBr3 / 24 h / 100 °C 7: 72 percent / (PPh3)2PdCl2 / dimethylformamide / 0.67 h / 20 - 100 °C | ||
Multi-step reaction with 8 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 85 percent / POBr3 / 24 h / 100 °C 8: 72 percent / (PPh3)2PdCl2 / dimethylformamide / 0.67 h / 20 - 100 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 85 percent / POBr3 / 24 h / 100 °C 7: 72 percent / (PPh3)2PdCl2 / dimethylformamide / 0.67 h / 20 - 100 °C |
Multi-step reaction with 8 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 85 percent / POBr3 / 24 h / 100 °C 8: 72 percent / (PPh3)2PdCl2 / dimethylformamide / 0.67 h / 20 - 100 °C | ||
Multi-step reaction with 7 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr 6: 85 percent / POBr3 / 24 h / 100 °C 7: 72 percent / (PPh3)2PdCl2 / dimethylformamide / 0.67 h / 20 - 100 °C | ||
Multi-step reaction with 8 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid 7: 85 percent / POBr3 / 24 h / 100 °C 8: 72 percent / (PPh3)2PdCl2 / dimethylformamide / 0.67 h / 20 - 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 80 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C | ||
Multi-step reaction with 4 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / Pd(OAc)2 / dimethylformamide / 20 - 140 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 98 percent / K2CO3 / Pd(OAc)2 / dimethylformamide / 0.67 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid | ||
Multi-step reaction with 5 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr |
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 99 percent / Pd(OAc)2 / dimethylformamide / 0.42 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid | ||
Multi-step reaction with 5 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 95 percent / aq. KOH / 24 h / 200 °C / 12929 Torr | ||
Multi-step reaction with 6 steps 1: 97 percent / conc. H2SO4 / 2.67 h / 20 - 100 °C 2: 83 percent / aq. sodium hydroxide; Br2 / 1 h / 20 - 70 °C 3: 82 percent / I2; isoamyl nitrite / acetonitrile / 0.33 h / 80 °C 4: 20 percent / (PPh3)2PdCl2 / dimethylformamide / 0.58 h / 100 °C 5: 97 percent / sodium amide / tetrahydrofuran / 13 h / 20 °C 6: KI; NaNO3; sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 1.) Na2S*9H2O / 1.) MeOH, H2O, reflux, 3 h, 2.) Et2O, H2O, 12 h 2: 86 percent / KOH / ethane-1,2-diol / 48 h / Heating 3: 59 percent / HCl gas / 12 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) Na2S*9H2O / 1.) MeOH, H2O, reflux, 3 h, 2.) Et2O, H2O, 12 h 2: 86 percent / KOH / ethane-1,2-diol / 48 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) Na2S*9H2O / 1.) MeOH, H2O, reflux, 3 h, 2.) Et2O, H2O, 12 h 2: 92 percent / conc. H2SO4 / 1.) reflux, 20 min, 2.) room temperature, 18 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 92 percent / 24 h / Ambient temperature 2: 81 percent / 15percent BuLi / hexane; tetrahydrofuran / 3 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 92 percent / 24 h / Ambient temperature 2: 15percent BuLi / hexane; tetrahydrofuran / -70 deg C to r.t., 30 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 92 percent / 24 h / Ambient temperature 2: 15percent BuLi / hexane; tetrahydrofuran / -70 deg C to r.t., 30 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 92 percent / 24 h / Ambient temperature 2: 17 percent / 15percent BuLi / hexane; tetrahydrofuran / 2 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In tetrahydrofuran at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In N,N-dimethyl-formamide at 20 - 100℃; for 23h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | at 80℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrazine hydrate at 80℃; for 1h; | |
99% | With hydrazine at 20℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 42% 2: 27% | at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(triphenylphosphine)palladium(II) dichloride; silver fluoride; triphenylphosphine In acetonitrile at 20 - 82℃; for 0.416667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 0 - 50 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 15 h / 0 - 50 °C 2.1: diborane; sodium hydrogencarbonate / chlorobenzene; Petroleum ether / 12 h / 0 - 50 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 50 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 0 - 50 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 15 h / 0 - 50 °C 2.1: diborane; sodium hydrogencarbonate / chlorobenzene; Petroleum ether / 12 h / 0 - 50 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 50 °C / Inert atmosphere 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 0 - 50 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide; water; Petroleum ether | ||
Multi-step reaction with 4 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 15 h / 0 - 50 °C 2.1: diborane; sodium hydrogencarbonate / chlorobenzene; Petroleum ether / 12 h / 0 - 50 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide; water; Petroleum ether / 20 °C | ||
Multi-step reaction with 4 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 50 °C / Inert atmosphere 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 1 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 0 - 50 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide; water; Petroleum ether 5.1: water; lithium hydroxide / tetrahydrofuran / 20 °C | ||
Multi-step reaction with 5 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 15 h / 0 - 50 °C 2.1: diborane; sodium hydrogencarbonate / chlorobenzene; Petroleum ether / 12 h / 0 - 50 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide; water; Petroleum ether / 20 °C 5.1: water; lithium hydroxide / tetrahydrofuran / 20 °C | ||
Multi-step reaction with 5 steps 1.1: sulfuric acid / 3 h / 135 °C 1.2: 0.5 h / 0 - 50 °C 2.1: diborane / chlorobenzene / 12 h / 50 °C / Inert atmosphere 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 1 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 5.1: lithium hydroxide; water / tetrahydrofuran / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: piperidine / butan-1-ol / 16 h / 20 °C 2: pyridine; disulfur dichloride / water / 12 h / 145 °C | ||
Multi-step reaction with 2 steps 1: piperidine / butan-1-ol / 16 h / 20 °C 2: pyridine; disulfur dichloride / 12 h / 145 °C | ||
Multi-step reaction with 2 steps 1: piperidine / butan-1-ol / 16 h / 20 °C 2: pyridine; disulfur dichloride / 12 h / 145 °C |
Multi-step reaction with 2 steps 1: piperidine / ethanol / 2 h / 90 °C 2: pyridine; disulfur dichloride / 16 h / 140 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 110℃; for 3h; Inert atmosphere; | 55 [0740] to a mixture of compound 96b (2.00 g, 9.06 mmol) in dioxane (150.00 ml) was added alme3 (2m, 20.00 ml) and pd(pph3)4 (1.05 g, 906.00 umol) under N2, then the reaction was stirred at 110 °C for 3h. The reaction mixture was cooled to room temperature and quenched with ice/h2o(100 ml) and EtOAc(150 ml), yellow solid was precipitate out, filtered and the filtrate was extracted with EtOAc(60 ml x 2), the combined organic was washed with brine (70 ml), dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by flash silica gel chromatography (isco;40 g sepaflash silica flash column, eluent of 0 ~ 10% ethyl acetate/petroleum ether gradient 40 ml/min) to give compound 96c (700.00 mg, 16.59% yield, 43% purity) as light yellow solid. 1H NMR (400mhz, chloroform-d) δ 7.79 - 7.75 (m, 2h), 7.56 - 7.51 (m, 3h), 2.67 (s, 3h). MS (ESI) m/z (M+H)+ 200.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 3 h / 110 °C / Inert atmosphere 2.1: sulfuric acid / 1.5 h / 135 °C 2.2: 1 h / 0 - 70 °C |