Phenyl Isothiocyanate
PTC · PITC · Isothiocyanatobenzene · R1 · PIT · Phenyl thiocyanate · Phenyl isothiocyanate,PITC · PHENYL ISOTHIOCYANATE SOLUTION, FOR PROT.SEQ. ANAL.
Identifiers & Physical Properties
| CAS No. | 103-72-0 |
|---|---|
| Molecular formula | C7H5NS |
| Average molar mass | 135.19 g/mol |
| Monoisotopic mass | 135.01427034 g/mol |
| SMILES | S=C=Nc1ccccc1 |
| InChIKey | QKFJKGMPGYROCL-UHFFFAOYSA-N |
| PubChem CID | 7673 |
| ChEMBL | CHEMBL309036 |
| ChEBI | CHEBI:85103 |
| EC No. | 203-138-1 |
| DTXSID | DTXSID0021129 |
Chemical & Physical Properties
| XLogP | 3.3 |
|---|---|
| Topological polar surface area | 44.5 |
| Hydrogen bond donors | 0 |
| Hydrogen bond acceptors | 2 |
| Rotatable bonds | 1 |
| Heavy atoms | 9 |
| Formal charge | 0 |
| Complexity | 121 |
| Vapor pressure | 1.5 [mmHg]10 hPa (20 °C) |
| Physical Description | Liquid[Merck Index] Colorless liquid[Sigma-Aldrich MSDS] |
| Kovats Retention Index | 11631138 |
| Melting point | −21 °C(lit.) |
| Boiling point | 218 °C(lit.) |
| Density | 1.132 g/mL at 20 °C(lit.) |
| Refractive index | n20/D 1.6515(lit.) |
| Flash point | 190 °F |
| Storage conditions | 2-8°C |
| Solubility | water: insolubleSoluble in alcohol, and ether. Insoluble in water. |
| Physical state | liquid |
| Specific gravity | 1.137 (20/4℃) |
| Color | Clear pale yellow to yellow |
| Sensitivity | Moisture Sensitive |
| Merck | 14,7297 |
| BRN | 471392 |
| Henry's law constant | 3.3×10-3 mol/(m3Pa) at 25℃, Duchowicz et al. (2020) |
| Dielectric constant | 10.7(20℃) |
| Stability | Stable. Combustible. Incompatible with strong oxidizing agents, strong acids. |
| InChI | 1S/C7H5NS/c9-6-8-7-4-2-1-3-5-7/h1-5H |
| InChIKey | QKFJKGMPGYROCL-UHFFFAOYSA-N |
| SMILES | S=C=Nc1ccccc1 |
| LogP (partition coefficient) | 3.280 |
| Surface tension | 41.5mN/m at 20°C |
| CAS DataBase Reference | 103-72-0(CAS DataBase Reference) |
| FDA UNII | 0D58F84LSU |
| NIST Chemistry Reference | Benzene, isothiocyanato-(103-72-0) |
| EPA Substance Registry System | Benzene, isothiocyanato- (103-72-0) |
| UNSPSC Code | 12352209 |
| NACRES | NA.31 |
| GHS pictogram | GHS05,GHS06,GHS09 |
| Signal word | Danger |
| GHS hazard statements | H301-H314-H410-H227 |
| GHS precautionary statements | P501-P273-P270-P210-P264-P280-P370+P378-P391-P303+P361+P353-P301+P330+P331-P363-P301+P310+P330-P304+P340+P310-P305+P351+P338+P310-P403+P235-P405 |
| Personal protective equipment (PPE) | Faceshields, Gloves, Goggles, type ABEK (EN14387) respirator filter |
| Hazard symbols | T,N,Xn,F |
| Risk statements (R) | 25-34-42/43-51/53-67-65-50/53-36/37/38-22-11-38-63-23/24/25-36/38 |
| Safety statements (S) | 9-16-29-33-60-61-62-36-26-23-45-36/37/39-38-28A-36/37 |
| UN transport number | UN 1993 3/PG 2 |
| Water hazard class (WGK) | 3 |
| RTECS number | NX9275000 |
| F | 19 |
| TSCA inventory status | TSCA listed |
| Customs code | 2930 90 98 |
| Hazard class | 6.1Acute Tox. 3 OralResp. Sens. 1Skin Corr. 1BSkin Sens. 1 |
| Packing group | II |
| Storage class | 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials |
| Toxicity | LD50 orally in Rabbit: 157 mg/kg |
| REACH registrations | Active |
| Limited quantities | 100ml (liquid) or 0.5 Kg (solid) |
| Excepted quantities | Max Inner Pack (1g or 1ml) and Max Outer Pack (500g or 500ml) |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 0.5% (1 of 214) of reports.DangerH301 (82.2%): Toxic if swallowed [Danger Acute toxicity, oral]H314 (79.4%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]H317 (79%): May cause an allergic skin reaction [Warning Sensitization, Skin]H318 (54.7%): Causes serious eye damage [Danger Serious eye damage/eye irritation]H334 (76.2%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]H341 (54.2%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]H361 (54.2%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]H400 (21.5%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]H410 (24.3%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]P203, P233, P260, P261, P264, P264+P265, P270, P271, P272, P273, P280, P284, P301+P316, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P321, P330, P333+P317, P342+P316, P362+P364, P363, P391, P403, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 214 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Reported as not meeting GHS hazard criteria per 1 of 214 reports by companies.There are 10 notifications provided by 213 of 214 reports by companies with hazard statement code(s).Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Regulatory information | Chemical: Benzene, isothiocyanato-Status: Active Update: 10-12-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/26134Phenyl isothiocyanate: Does not have an individual approval but may be used under an appropriate group standard |
| Hazards summary | Dermal studies of guinea pigs demonstrate severe irritation, good absorption, and sensitizationEffects on thyroid function (decreased serum T4 levels) observed in 4-week oral study of rats[EPA - PPRTV] Causes burns and lachrymationMay cause skin and respiratory sensitizationInhalation may cause corrosive injuries to upper respiratory tract and lungsHarmful by ingestionTargets the kidney and bladder[Sigma-Aldrich MSDS] |
| Hazard Classes and Categories | Acute Tox. 3 (82.2%)Skin Corr. 1B (79.4%)Skin Sens. 1 (79%)Eye Dam. 1 (54.7%)Resp. Sens. 1 (76.2%)Muta. 2 (54.2%)Repr. 2 (54.2%)Aquatic Acute 1 (21.5%)Aquatic Chronic 1 (24.3%) |
| Treatment | EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration. |
| Health effects | Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L96, L97) |
| Adverse effects | Dermatotoxin - Skin burns.Lacrimator (Lachrymator) - A substance that irritates the eyes and induces the flow of tears.Skin Sensitizer - An agent that can induce an allergic reaction in the skin.Toxic Pneumonitis - Inflammation of the lungs induced by inhalation of metal fumes or toxic gases and vapors. |
| Exposure routes | Inhalation (L96)oral (L96)dermal (L96) |
| Toxicity summary | Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97) |
| Signs and Symptoms | Cyanide poisoning is identified by rapid, deep breathing and shortness of breath, general weakness, giddiness, headaches, vertigo, confusion, convulsions/seizures and eventually loss of consciousness. (L96, L97) |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Toxicity Data | LD50: 87 mg/kg (Oral, Mouse) (L565) LD50: 250 mg/kg (Subcutaneous, Mouse) (L565) LD50: 100 mg/kg (Intraperitoneal, Mouse) (L565) |
| RAIS Toxicity Values | 0.0002SCREEN Current0.002PPRTV Current |
| EPA Provisional Peer-Reviewed Toxicity Values | Phenyl Isothiocyanate2 x 10^-3 mg/kg-dayPDF DocumentInadequate information to assess carcinogenic potential2009 |
| Hazard Quotient Level 0.1 or Cancer Risk Level 1E-06 | 1.60e+012.30e+022.60e+001.5E+01(G)1.70e-032.00e-04 |
| Hazard Quotient Level 3 or Cancer Risk Level 1E-04 | 4.70e+017.00e+027.90e+001.5E+01 (G)2.00e-04Volatile |
| F | 19 |
| Personal protective equipment (PPE) | Faceshields, Gloves, Goggles, type ABEK (EN14387) respirator filter |
| Water hazard class (WGK) | 3 |
| TSCA inventory status | TSCA listed |
| RTECS number | NX9275000 |
| UN transport number | UN 1993 3/PG 2 |
| Customs code | 2930 90 98 |
| Toxicity | LD50 orally in Rabbit: 157 mg/kg |
| Risk statements (R) | 25-34-42/43-51/53-67-65-50/53-36/37/38-22-11-38-63-23/24/25-36/38 |
| Signal word | Danger |
| GHS pictogram | GHS05,GHS06,GHS09 |
| Hazard symbols | T,N,Xn,F |
| Safety statements (S) | 9-16-29-33-60-61-62-36-26-23-45-36/37/39-38-28A-36/37 |
| Hazard class | 6.1Acute Tox. 3 OralResp. Sens. 1Skin Corr. 1BSkin Sens. 1 |
| Storage class | 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials |
| Packing group | II |
| GHS hazard statements | H301-H314-H410-H227 |
| Limited quantities | 100ml (liquid) or 0.5 Kg (solid) |
| Excepted quantities | Max Inner Pack (1g or 1ml) and Max Outer Pack (500g or 500ml) |
| REACH registrations | Active |
| GHS precautionary statements | P501-P273-P270-P210-P264-P280-P370+P378-P391-P303+P361+P353-P301+P330+P331-P363-P301+P310+P330-P304+P340+P310-P305+P351+P338+P310-P403+P235-P405 |
Applications & Uses
Uses
Phenyl isothiocyanate is the reagent of choice in automated Edman degradation systems. However, this reagent is highly toxic and for manual modification other reagents are preferred such as dimethy laminoazobenzene isothiocyanate (Chang, 1983; Wang et al, 2000) or trifluoroethyl isothiocyanate (Bartlet-Jones et al, 1994). This last reagent has the advantage of being volatile, so that the excess of reagent is easily removed by vacuum before MS analysis (Spengler, 1997). This compound was used successfully during seven successive cycles of manual cleavage coupled with MS analysis. Nevertheless, the high reactivity of such compounds seems to shows artefactual modification such as“acetylation' of the hydroxyl groups of the Ser and Thr. Allyl isothiocyanate shows better selectivity, but again this reagent is toxic and difficult to use in manual approaches (Gu & Preswich, 1997) .
Uses
Phenyl isothiocyanate acts as a derivatizing reagent for primary and secondary amines. It is used in sequencing peptides by Edman degradation and in amino acid analyses by HPLC. It is used for derivatizing N-terminal amino acids of proteins for automated sequential analysis. It is a synthon for dithiadiazafulvalenes.
General Description
Phenyl isothiocyanate is an aromatic isothiocyanate. It participates in dehydration reactions of alcohols. It is widely used for synthesis of various biologically important heterocyclic compounds.
Preparation & Synthesis
Preparation
Synthetic procedure for phenyl isothiocyanate in 1-mol scaleInto a 2-L jacketed flask, 91.2 g of CS2 (1.2 mol) was dropwise added to a mixture of aniline (93.0 g, 1.0 mol) and K2CO3 (276.0 g, 2.0 mol) in 700 mL of water at room temperature within a period of 2.5 h. After the addition was complete, the mixture was stirred another 2 h. Then, the mixture was cooled to 0 °C, and a solution of 92.3 g of TCT (0.5 mol) in 450 mL of CH2Cl2 was dropwise added within 4 h. After the addition was complete, the mixture was stirred another 1 h to complete the conversion. The resulting mixture was basified to pH >11 with 250 mL of 6 N NaOH and yielded a clear solution. The organic layer was separated and the aqueous layer was extracted with 150 mL of CH2Cl2. The combined organic layers were dried over anhydrous Na2SO4, filtered, and the solvent of filtrate was removed via distillation under atmospheric pressure with a 25-cm Vigreux column. The residue was vacuum distilled and the desired product fraction was collected at 72–74 °C/1 mmHg. Finally, 127.0 g of colorless liquid (94%) was obtained.