64359-81-5

Basic information

• Product Name: 4,5-Dichloro-2-octyl-isothiazolone
• Synonyms: 4,5-dichloro-2-n-oct;5-Dichloro-2-octyl-3(2H)-isothiazolone;2-(4,5-dichlorooctyl)-2,3-dihydro-1,2-thiazol-3-one;DCOIT-99;DCOIT-30;4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one;4,5-DICHLORO-2-N-OCTYL-3(2H)-ISOTHIAZOLONE;4,5-dichloro-2-octyl-3(2h)-isothiazolone
• CAS NO: 64359-81-5
• Molecular Formula: C₁₁H₁₇Cl₂NOS
• Molecular Weight: 282.23
• EINECS: 264-843-8
• Product Categories: antibacterial agent;Preservative;Industrial/Fine Chemicals
• Mol File: 64359-81-5.mol
• Article Data: 24

Chemical Properties

• Melting Point: 40.0 to 44.0 °C
• Boiling Point: 322.6 °C at 760 mmHg
• Flash Point: 148.9 °C
• Appearance: solid
• Density: 1.25 g/cm³
• Vapor Pressure: 0.000276mmHg at 25°C
• Refractive Index: 1.552
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: -6.09±0.60(Predicted)
• Stability: Air Sensitive
• Merck: 14,3070
• CAS DataBase Reference: 4,5-Dichloro-2-octyl-isothiazolone(CAS DataBase Reference)
• NIST Chemistry Reference: 4,5-Dichloro-2-octyl-isothiazolone(64359-81-5)
• EPA Substance Registry System: 4,5-Dichloro-2-octyl-isothiazolone(64359-81-5)

Safety Data

• RIDADR: 3077
• RTECS: NX8157075
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 64359-81-5(Hazardous Substances Data)

Usage

Corrosivity

The chemical and formulations containing the chemical applied to intact rabbit skin produced severe erythema, oedema and scar formation. The exposed areas had effects that were not reversible. Data indicates corrosive effects in the respiratory tract. While no data are available for effects in the eyes, the chemical is deemed to capable of causing severe damage. There is sufficient evidence to warrant hazard classification.

Description

As an irritant and sensitizer, Kathon 930 caused contact dermatitis in employees of a textile finishing factory.

Chemical Properties

solid

Definition

ChEBI: A 1,2-thiazole that is 1,2-thiazol-3(2H)-one substituted by chloro groups at positions 4 and 5 and an octyl group at position 2. It is used as a fungicide.

Application

Suitable for applications in the paints and coatings, wood, and leather fields to resist corrosion and protect against mildews and algae.

Health Hazard

The chemical is referred to as 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in this assessment. Where available, data for two commercial antifouling products C-9211 HQ (32.6 % of DCOIT in xylene) and Acticide? DCOIT (97.1% purity) are used for some health end-points. The information on health hazards is primarily obtained from the comprehensive reviews from the Norwegian Environment Agency as part of its ECHA CLH proposal (ECHA, 2018) and an EU (Norway) DCOIT evaluation for the use of DCOIT as a biocide in antifouling products (EU, 2014). Unless otherwise noted, references to individual studies below are taken from these reviews.

Contact allergens

Irritant and sensitizer, Kathon? 930 caused contact dermatitis in employees of a textile fnishing factory.

Toxicology

The chemical, DCOIT is moderately absorbed through skin and moderately absorbed via oral route. It is then extensively distributed to tissues (liver, kidney, stomach and intestine) and metabolised following oral administration. In a study conducted in rats, 81–93 % of orally administered 14C-DCOIT was excreted primarily in the faeces within a 2-day period. Plasma elimination half-life of 14C-DCOIT was 16.1–19.4 hours for males and 20.5–25.0 hours for females. The highest concentration of 14C-DCOIT was found in liver, stomach, intestine and kidney. More than 80 % of the administered dose was eliminated via faeces, 11–18 % was eliminated via urine and less than 2 % of the dose was eliminated through exhaled air. DCOIT metabolised to form six metabolites in the faeces and eight metabolites in the urine. Degradation of DCOIT involves cleavage of the ring and subsequent oxidation of 7–18 % of the administrated dose to N-(n-octyl) malonamic acid (NNOMA, major metabolite), N-(n-octyl)acetamide, N-(n-octyl)oxamic acid and N-(n-octyl)-β-acetyl propionamide. The chemical undergoes subsequent biotransformation involving hydroxylation, dealkylation and acetylation (EU, 2014; ECHA, 2018).

in vitro

In a bacterial gene mutation test, DCOIT was tested in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 up to a maximum concentration of 300 μg/plate with negative responses in all strains with and without metabolic activation (EU, 2014; ECHA, 2018).

in vivo

In two micronucleus assays, DCOIT was tested in CD-1 mice (5-9 mice/sex/dose) at doses up to 325 mg/kg bw/day by gavage. No genotoxicity was reported in both studies (EU, 2014; ECHA, 2018).

Precautions

1. Suitable for use in all marine paints. Can effectively kill many bacteria and mildews like penicillium notatum, basidiomycetes, aspergillus niger, fusarium, and curvularia. Can be added at any production step for use; it is recommended to adopt the concentration of 5 ~ 15% (w/w).2. Operational instruction must be strictly followed. Avoid any contact with the skin. Wear protective clothes, goggles, and rubber gloves in operation. Once any contact with the skin happens, wash the skin immediately with plenty of water and soaps; when it splashes into eyes, wash immediately with plenty of water and buffer solutions.

InChI:InChI=1/C11H17Cl2NOS/c1-2-3-4-5-6-7-8-14-11(15)9(12)10(13)16-14/h2-8H2,1H3

Synthetic route

3,3'-disulfanediylbis(N-octylpropanamide) (33312-01-5) → Sea-Nine 211 (64359-81-5)

Conditions	Yield
Stage #1: N,N'-dioctyl-3,3'-dithiodipropionamide With thionyl chloride In chloroform at 35℃; for 0.833333h; Stage #2: With chlorine In chloroform at 35℃; for 2h; Reagent/catalyst; Solvent; Temperature;	88.1%
With chlorine In chlorobenzene at 55 - 65℃; Temperature; Solvent; Flow reactor; Large scale;	1350 kg

3,3'-disulfanediylbis(N-octylpropanamide) (33312-01-5) → Sea-Nine 211 (64359-81-5) + 2-octyl-isothiazol-3-one (26530-20-1)

Conditions	Yield
Stage #1: N,N'-dioctyl-3,3'-dithiodipropionamide With sulfuryl dichloride for 9.5h; Stage #2: With chlorine at 40 - 45℃; for 15h;	A 56.5% B 19%

sulphur dichloride + acrylic acid octylamide (10124-68-2) → Sea-Nine 211 (64359-81-5)

Conditions	Yield
With triethylamine In chlorobenzene	22%

2-octyl-isothiazol-3-one (26530-20-1) → Sea-Nine 211 (64359-81-5)

Conditions	Yield
With sulfuryl dichloride In ethyl acetate at 70℃;
With chlorine at 40℃;

n-octyl 3-mercaptopropanamide → Sea-Nine 211 (64359-81-5) + 2-octyl-4-bromo-5-chloro-3-isothiazolone

Conditions	Yield
Stage #1: n-octyl 3-mercaptopropanamide With chlorine In 1,2-dichloro-ethane at 35 - 40℃; Inert atmosphere; Stage #2: With bromine In 1,2-dichloro-ethane

n-octyl 3-mercaptopropanamide → Sea-Nine 211 (64359-81-5)

Conditions	Yield
Stage #1: n-octyl 3-mercaptopropanamide With chlorine In chlorobenzene at 45 - 50℃; Flow reactor; Stage #2: With chlorine In chlorobenzene at 55 - 65℃; Flow reactor;	110 g

Sea-Nine 211 (64359-81-5) + 2-mercaptopyridine-1-oxide sodium salt (3811-73-2) → [4-chloro-2-(n-octyl)-3-isothiazolon-5-yl]-(1-oxypyridin-2-yl)sulfide

Conditions	Yield
With sodium hydroxide In ethanol; water for 4h; pH=8.5;	82%

Sea-Nine 211 (64359-81-5) + 2-mercaptopyridine-1-oxide sodium salt (3811-73-2) → [4-chloro-2-(n-octyl)-3-isothiazolon-5-yl]-(1-oxypyridin-2-yl)sulfide

Conditions	Yield
With sodium hydroxide In ethanol; dichloromethane	0.9 g (82%)

Sea-Nine 211 (64359-81-5) + zinc 5,10,15,20-tetrakis(4-methylphenyl)porphyrin (19414-67-6) → C48H36N4(2-)*C11H17Cl2NOS*Zn(2+)

Conditions	Yield
In methanol; water for 1h;	310 g

Upstream product

• 10124-68-2 acrylic acid octylamide 
• 33312-01-5 3,3'-disulfanediylbis(N-octylpropanamide) 
• 26530-20-1 2-octyl-isothiazol-3-one 

Relevant articles and documents

Method for coproducing OIT and DCOIT

The invention discloses a method for coproducing OIT and DCOIT. The method comprises the following steps: adding a raw material N, N'-di-n-octyldithiodipropionamide or N-n-octylmercaptopropionamide and a solvent into a chlorination reaction kettle, introducing chlorine, and carrying out solid-liquid separation on the material in the reaction kettle after the reaction is finished; distilling the obtained mother liquor under reduced pressure, and reserving kettle residues for later use; transferring the obtained filter cake to a neutralization kettle, adding a solvent and alkali liquor for neutralization and liquid separation to obtain an organic layer; carrying out water washing, desolventizing and filtering part on the organic layer to obtain the OIT finished product; carrying out azeotropic dehydration on the other part of the organic layer, combining with the kettle residues, introducing chlorine for chlorination, adding an alkali liquor into reaction liquid obtained after the reaction is finished for neutralization, and filtering; and recrystallizing the obtained filter cake, and leaching and drying the obtained solid to obtain the DCOIT finished product. According to the invention, the production efficiency is improved, the product quality is improved, and the method is an efficient and environment-friendly production method.

Preparation method of 3-isothiazolinone compound

The invention discloses a preparation method of a 3-isothiazolinone compound, which comprises the following steps of adding raw materials and a solvent into a reaction system, and stirring and mixing,adding a dehydrating agent into the mixed solution, and stirring for reaction, introducing chlorine into the reaction system, stirring the reaction mixture for reaction, filtering and separating to obtain a product. According to the method, the chemical dehydrating agent is added into the reaction system to react with water or alcohol in the reaction system, so that water or alcohol in the systemis removed, side reaction caused by water or alcohol is avoided, the reaction yield is increased, and the economic benefit is remarkable.

Preparation method of 2-n-octyl-4-bromo-5-chloro-3-isothiazolone

The invention discloses a preparation method of 2-n-octyl-4-bromo-5-chloro-3-isothiazolone, and belongs to the technical field of organic chemistry. According to the preparation method, 3-mercapto-N-n-octylpropionamide, sulfonyl chloride, and bromine are taken as the raw materials, 1, 2-dichloroethane is taken as the solvent, the raw materials are heated to carry out chlorine cyclization and bromination reactions to generate a mixture composed of 2-n-octyl-4-bromo-5-chloro-3-isothiazolone, 2-n-octyl-4,5-dichloro-3-isothiazolone, and other impurities, then the mixture is subjected to recrystallization and column chromatography to obtain pure 2-n-octyl-4-bromo-5-chloro-3-isothiazolone, and the yield is 35 to 43%. The provided preparation method overcomes the shortages of conventional synthesis technology. A novel synthesis method of 2-n-octyl-4-bromo-5-chloro-3-isothiazolone is provided.