2-Thiopheneethanol

1. Description clear colorless to slightly brown liquid http://www.echemi.com/ http://www.echemi.com/ Basic Attributes CAS No：5402-55-1 Molecular Formula ：C6H8OS Molecular Mass ：128.19 Exact Mass ：128.029587 PSA ：48.5 A^2 LogP ：1.3 EINECS ：226-452-0 InChIKeys ：VMJOFTHFJMLIKL-UHFFFAOYSA-N H-bond Acceptor ：2 H-bond Donor ：1 SP3 ：0.33 RBN ：2 Characteristics Appearance ：Clear light yellow to gray-green or brownish Liquid Density ：1.153 g/mL at 25 °C(lit.) Bolling Point ：108-109 °C13 mm Hg(lit.) Flash Point ：214 °F Refractive Index ：n20/D 1.551(lit.) Solubility ：slightly soluble Storage Condition ：Store below +30°C.

2. BRN ：106985 Safety Information HS Code ：29349990 UN No. ：UN 3334 WGK_Germany ：3 Risk Code ：36/37/38 Safety Instructions ：23-24/25-36-26 Dangerous Mark ：Xi P Code ：P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501 Hazard Statements ：H302 Hazard Note ：Irritant Product Usage 2-Thiopheneethanol is a thiophene derivative used in the preparation of oligothiophene isothiocyanates as fluorescent markers for biopolymers. 2-Thiopheneethanol is also used in the preparation of other biologically active compounds such as the analgesic Sulfentanyl and the antithrombotic Clopidogrel Hydrogen Sulfate (C587250).

3. Production Methods Biotransformation experimentsFungal strains were pre-grown in Petri dishes containing maltextract solid medium (MEA: 20 g L−1 glucose, 20 g L−1 malt extract,20 g L−1 agar, 2 g L−1 peptone) from which the inoculum for liquidcultures was set up. The fungus was inoculated as conidia suspen-sion (1 106 conidia/mL) in 50 mL asks containing 40 mL of maltextract liquid medium. Flasks were incubated at 25 C and weremaintained under agitation (110 rpm).After 2 days of pre-growth, a 500 mM solution of the substratein DMSO was added, to a starting substrate concentration (c0) of1–5 mM. For each substrate, three biological replicates were run.The experiment was run for 3 days after the addition of the sub-strates, during which time 1 mL samples were taken, at speciedintervals (usually 24, 48, and 72 h). Each sample was extractedwith EtOAc (500 L), the organic phase was dried over anhydrousNa2SO4 and analysed by means of GC/MS. In some cases (see Section2.4) the isolation of the reduced product has been carried out.For each set of biotransformations, one ask was used to mea-sure the initial biomass and pH before the addition of the substrate.These parameters were also evaluated at the end of the experimentfor all the asks. The liquid media was separated from the biomassby ltration and was used for pH measurement while the myceliawere dried at 60 C for 24 h to measure the biomass dry weight. 2-(Thiophen-2-yl)ethanol: from 2-(thiophen-2-yl)acetic acid(3.7 mg, 72percent) and from methyl 2-(thiophen-2-yl)acetate (24.6 mg,96percent). 1H NMR (400 MHz, CDCl3, TMS): = 7.20 (m, 1H, heteroaro-matic hydrogen), 6.99 (m, 1H, heteroaromatic hydrogen), 6.90 (m,1H, heteroaromatic hydrogen), 3.85 (t, 2H, J = 6.2 Hz, CH2OH), 3.02(t, 2H, J = 6.2 Hz, CH2CH2OH). 13C NMR (100 MHz, CDCl3, TMS): = 140.5, 127.0, 125.8, 124.0, 63.4, 33.3. GC/MS: tR = 9.47 min, m/z128 (M+, 30), 110 (5), 97 (100)Step 9 2.3. Biotransformation experimentsFungal strains were pre-grown in Petri dishes containing maltextract solid medium (MEA: 20 g L−1 glucose, 20 g L−1 malt extract,20 g L−1 agar, 2 g L−1 peptone) from which the inoculum for liquidcultures was set up. The fungus was inoculated as conidia suspen-sion (1 106 conidia/mL) in 50 mL asks containing 40 mL of maltextract liquid medium. Flasks were incubated at 25 C and weremaintained under agitation (110 rpm).After 2 days of pre-growth, a 500 mM solution of the substratein DMSO was added, to a starting substrate concentration (c0) of1–5 mM. For each substrate, three biological replicates were run.The experiment was run for 3 days after the addition of the sub-strates, during which time 1 mL samples were taken, at speciedintervals (usually 24, 48, and 72 h). Each sample was extractedwith EtOAc (500 L), the organic phase was dried over anhydrousNa2SO4 and analysed by means of GC/MS. In some cases (see Section2.4) the isolation of the reduced product has been carried out.For each set of biotransformations, one ask was used to mea-sure the initial biomass and pH before the addition of the substrate.These parameters were also evaluated at the end of the experimentfor all the asks. The liquid media was separated from the biomassby ltration and was used for pH measurement while the myceliawere dried at 60 C for 24 h to measure the biomass dry weight. 2-(Thiophen-2-yl)ethanol: from 2-(thiophen-2-yl)acetic acid(3.7 mg, 72percent) and from methyl 2-(thiophen-2-yl)acetate (24.6 mg,96percent). 1H NMR (400 MHz, CDCl3, TMS): = 7.20 (m, 1H, heteroaro-matic hydrogen), 6.99 (m, 1H, heteroaromatic hydrogen), 6.90 (m,1H, heteroaromatic hydrogen), 3.85 (t, 2H, J = 6.2 Hz, CH2OH), 3.02(t, 2H, J = 6.2 Hz, CH2CH2OH). 13C NMR (100 MHz, CDCl3, TMS): = 140.5, 127.0, 125.8, 124.0, 63.4, 33.3. GC/MS: tR = 9.47 min, m/z128 (M+, 30), 110 (5), 97 (100)General procedure: Phenethyl alcohol (3a) A two neck Schlenk flask equipped

4. with a magnetic stirring bar and septum was heated with heat gun (~400 °C) for 10 min under high vacuum. After cooling to room temperature, the flask was flushed with argon (3 times). Zn-dust (654 mg, 2.0 equiv, 10.0 mmol) was added followed by THF (20 mL). 1,2-Dibromoethane (5 molpercent) was added and the reaction mixture was heated until ebullition occurs. After cooling to rt, chlorotrimethylsilane (1 molpercent) was added and the mixture was heated again till ebullition occurs. The flask was again cooled to rt and benzyl chloride (633 mg, 5.0 mmol, 1 equiv) was added as a solution in THF (10 mL) and it was heated at 70 °C for 2 h and cooled to rt. Paraformaldehyde (450 mg, 3.0 equiv. 15.0 mmol) was slowly added at rt and the flask was again heated at 70 °C for 6 h. The solution was cooled to rt and saturated NH2-Ethyl-2-ethanol a) Preparation of the Sodium Suspension 53 g (61 ml) of toluene, 0.0265 g of polyethylene and 26.5 g (1.15 mol) of sodium cut into pieces are placed in a 250 ml round-bottomed flask under nitrogen, equipped with a stirrer and a condenser. The mixture is heated to 102° C. and then stirred for 0.5 hour. The suspension is then cooled to a temperature of between 20° C. and 25° C. b) Metallation of the Thiophene 145.4 g (133.7 ml; 1.731 mol) of thiophene are placed in a 1 l jacketed reactor under nitrogen, equipped with a dropping funnel and cooled with chilled dichloromethane. The mixture is cooled to 0° C..+-.1° C. with stirring. The sodium suspension is then diluted, followed by addition to the thiophene. While keeping the temperature at 0° C..+-.1° C., this thiophene/sodium suspension is then added to a mixture of 51.8 g (76 ml; 0.762 mol) of isoprene in 166 g (187 ml; 2.3 mol) of tetrahydrofuran maintained at 0° C..+-.1° C. Under these conditions, the introduction time is about 1.5 h. The reaction is then maintained at 0° C..+-.1° C. for 2 hours. c) Oxyethylenation 55.8 g (1.270 mol) of ethylene oxide are added to the mixture obtained in paragraph b) above, via a dip tube, while maintaining the temperature at 20° C..+-.1° C. The duration of this addition is about 1.5 h. The suspension is then stirred for 0.5 h at 20° C..+-.1° C. d) Hydrolysis 300 ml of water and 74 g of ammonium chloride are placed in a 2 l reactor equipped with a cooling and stirring system. This solution is cooled to a temperature of between -5° C. and 0° C. and the reaction mixture obtained in paragraph c) is then transferred, by nitrogen pressure, over 10 to 15 minutes, onto the ammonium chloride solution. Under these conditions and with a cooling bath containing ice and methanol, the temperature at the end of hydrolysis is 20° C. The mixture is stirred for 15 minutes at 20° C..+-.2° C., the phases are separated by settling for 15 minutes and the (upper) organic phase is washed 3 times at 20° C..+-.2° C. with 200 ml of water. The combined aqueous phases are extracted 3 times at 20° C..+-.2° C. using 100 ml (86 g) of toluene. The organic phases are pooled and the toluene solution is concentrated under vacuum (50° C.; 15 mmHg). In this way, 133 g of crude 83percent.2-Ethyl-2-ethanol a) Preparation of the Sodium Suspension 69 g (80 ml) of toluene, 0.0230 g of oleic acid and 23 g (1 mol) of sodium cut into pieces are placed in a 250 ml round-bottomed flask under nitrogen, equipped with a stirrer and a condenser. The mixture is heated to 102° C. and then stirred for 0.5 hour. The suspension is then cooled to a temperature of between 20° C. and 25° C. b) Metallation of the Thiophene 126 g (1.5 mol ) of thiophene are placed in a 1 l jacketed reactor under nitrogen, equipped with a dropping funnel and cooled with chilled isopropanol. The mixture is cooled to 0° C..+-.1° C. with stirring. The sodium suspension is then diluted, followed by addition to the thiophene. While keeping the temperature at 0° C..+-.1° C., this thiophene/sodium suspension (76 ml; 0.762 mol) is then added to a mixture of 79 g (0.670 mol) of α-methylstyrene in 144 g (2 mol) of tetrahydrofuran 2-thienyl-2-ethanol are obtained. Yield:

5. maintained at 0° C..+-.1° C. Under these conditions, the introduction time is about 1.5 h. The reaction medium is then maintained at 0° C..+-.1° C. for 2 hours. c) Oxyethylenation 48 g (1.1 mol) of ethylene oxide are added to the mixture obtained in paragraph b) above, via a dip tube, while maintaining the temperature at 20° C..+-.1° C. The duration of this addition is about 1.5 h. The suspension is then stirred for 0.5 h at 20° C..+-.1° C. d) Hydrolysis 230 ml of water are placed in a 2 l reactor equipped with a cooling and stirring system. This solution is cooled to a temperature of between 0° C. and 5° C. and the reaction medium obtained in paragraph c) is then transferred into the water, over 10 to 15 minutes. Under these conditions and with a cooling bath containing ice and methanol, the temperature at the end of hydrolysis is in the region of 20° C. The phases are separated by settling and the upper organic phase is concentrated under vacuum (50° C.; 15 mmHg). In this manner, 239 g of crude 2-thienyl-2-ethanol are obtained. Yield: 83percent.Preparation of 2-thienyl-2-ethanol a) Preparation of the Sodium Suspension 84.3 g of dry toluene, 0.32 ml of oleic acid and 28.1 g (1.2217 mol) of sodium cut into pieces are placed into a 250 ml round-bottomed flask under nitrogen, equipped with a stirrer and a condenser. The mixture is heated to 102° C. and then stirred for 0.5 h. The suspension is then cooled to a temperature in the region of 25° C. b) Metallation of the Thiophene 154.2 g (1.5 equivalents) of thiophene are placed in a jacketed 1 l reactor under a nitrogen atmosphere, equipped with a dropping funnel and cooled. The flask is cooled to 0° C. with stirring and the sodium suspension is added to the thiophene. 2,3-dimethyl-1,3-butadiene are added to 176 g (2 equivalents) of tetrahydrofuran, while keeping the temperature at 0° C..+-.1° C. The reaction medium is then maintained at 0° C. for 2 hours. c) Oxyethylenation 59.2 g of ethylene oxide are added, via a dip tube, to the mixture obtained in paragraph b) above, while keeping the temperature below or equal to 20° C. The reaction medium is then left for 20 minutes at 20° C. with stirring. d) Hydrolysis The suspension obtained in paragraph c) is transferred, over 5 minutes and under a nitrogen pressure, into a 2 liter reactor containing 281 g of ice under nitrogen. The temperature of the medium at the end of introduction is 13° C. The mixture is stirred for 30 minutes and the phases are separated by settling. The organic phase is extracted with 100 ml of toluene, stirred for 30 minutes and the phases are separated by settling. The organic phase is then concentrated under vacuum. In this way, 145.6 g of 2-thienyl-2-ethanol are obtained. Yield: 83percent. 67.2 g (0.67 equivalent) of