50512-35-1

Basic information

• Product Name: Isoprothiolane
• Synonyms: Diisopropyl 2-(1,3-dithiolan-2-ylidene)malonate;di-Isopropyl1,3-dithiolan-2-ylidenemalonate;Diisopropyl1,3-dithiolan-2-ylidenemalonate;di-isopropyl1,3-dithiolane-2-ylidenemalonate;diisopropyl-2(1,3-dithiolan-2-ylidene)malonate;Fudiolan;Fuji 1;fuji1
• CAS NO: 50512-35-1
• Molecular Formula: C₁₂H₁₈O₄S₂
• Molecular Weight: 290.4
• Product Categories: FUNGICIDE
• Mol File: 50512-35-1.mol
• Article Data: 3

Chemical Properties

• Melting Point: 54°C
• Boiling Point: 402.48°C (rough estimate)
• Flash Point: 159 °C
• Appearance: /
• Density: 1.3402 (rough estimate)
• Vapor Pressure: 3.7E-05mmHg at 25°C
• Refractive Index: 1.4950 (estimate)
• Storage Temp.: 0-6°C
• Water Solubility: 54 mg l-1 (25 °C)
• BRN: 2128528
• CAS DataBase Reference: Isoprothiolane(CAS DataBase Reference)
• NIST Chemistry Reference: Isoprothiolane(50512-35-1)
• EPA Substance Registry System: Isoprothiolane(50512-35-1)

Safety Data

• Hazard Codes: Xn,N
• Statements: 22-51/53
• Safety Statements: 61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 50512-35-1(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 50512-35-1 differently. You can refer to the following data:
1. Isoprothiolane is a dithiolane pesticide. Isoprothiolane is commonly used in agriculture as a fungicide to control planthoppers and blast disease in rice plants.
2. Isoprothiolane is a fungicide that is used to control rice blast (Pyriculuriu aryzae), rice stem rot and Fusarium leaf spot on rice. It also reduces the plant-hopper population on rice.

Hazard

Moderately toxic by ingestion.

Metabolic pathway

Isoprothiolane is easily oxidized by rat liver 9000 g supernatant to produce its racemic sulfoxide in this process, NADPH is an effective cofactor but NADH is not. The liver microsomes, however, preferentially form its (?+)-isomer in an enantiomeric excess of 38-43%. The sulfoxidation of isoprothiolane by rice plants proceeds too slowly to determine the metabolites. Both isoprothiolane (+?)- and (-)- sulfoxides undergo rapid racemization by rat cytosol (105 000 g supernatant) or rice plants, accompanied with reduction to isoprothiolane.

Degradation

Half-lives of isoprothiolane in river water were greater than 50 days (Hayakawa et. al., 1992). The compound is decomposed slowly in deionised water under UV light or sunlight. In rice paddy water, photodegradation was greatly accelerated by the presence of natural organic constituents (Chou and Eto, 1980; Eto et al., 1979). Isoprothiolane was placed on a silica gel TLC plate and irradiated at 10 cm distance with a 10 W lamp emitting mainly at 254 nm. Isoprothiolane photodegraded rapidly (half-life about 3 hours). Five products were detected. Proposed pathways of photodegradation are shown in Scheme 1 and involved cleavage of the dithiolane ring, ester hydrolysis, decarboxylation and the formation of dimeric heterocyclic compounds. The identities of oxalic acid (2), dithiolanylidenemalonic acid (3), dithiolanylideneacetic acid (4), 2,4- bis[bis(isopropoxycarbonyl)methylene]-1,3-dithietane (5), 3,5-bis[bis(isopropoxycarbonyl) methylene]-1,2,4-trithiolane (6) and elemental sulfur were confirmed. Isoprothiolane degraded more rapidly on sand than on a glass plate (Chou and Eto, 1980).

InChI:InChI=1/C12H18O4S2/c1-7(2)15-10(13)9(11(14)16-8(3)4)12-17-5-6-18-12/h7-8H,5-6H2,1-4H3

Synthetic route

3-{2-[2-(2,2-Bis-isopropoxycarbonyl-1-methoxy-vinylsulfanyl)-ethyldisulfanyl]-ethylsulfanyl}-2-isopropoxycarbonyl-3-methoxy-acrylic acid isopropyl ester (147848-85-9) → isoprothiolane (50512-35-1)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran; methanol 1.) 3 d, room temperature, 2.) 2 h, reflux;	64%

2-[(2-Ethyldisulfanyl-ethylsulfanyl)-ethylsulfanyl-methylene]-malonic acid diisopropyl ester (147848-87-1) → isoprothiolane (50512-35-1)

Conditions	Yield
With sodium carbonate In methanol; water Ambient temperature;	47%

methanol (67-56-1) + Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1-oxide (52303-69-2, 108114-60-9, 108114-61-0) → isoprothiolane (50512-35-1) + 2-[Methoxy-(2-methoxysulfinyl-ethylsulfanyl)-methylene]-malonic acid diisopropyl ester + 3-{2-[2-(2,2-Bis-isopropoxycarbonyl-1-methoxy-vinylsulfanyl)-ethyldisulfanyl]-ethylsulfanyl}-2-isopropoxycarbonyl-3-methoxy-acrylic acid isopropyl ester (147848-85-9)

Conditions	Yield
With sodium carbonate for 0.5h; Ambient temperature;	A 17% B 31% C 40%

C26H42O11S4 (147848-84-8) → isoprothiolane (50512-35-1) + 2-[Methoxy-(2-methoxysulfinyl-ethylsulfanyl)-methylene]-malonic acid diisopropyl ester + 3-{2-[2-(2,2-Bis-isopropoxycarbonyl-1-methoxy-vinylsulfanyl)-ethyldisulfanyl]-ethylsulfanyl}-2-isopropoxycarbonyl-3-methoxy-acrylic acid isopropyl ester (147848-85-9)

Conditions	Yield
With sodium carbonate In methanol; water for 12h; Ambient temperature;	A 5% B 27% C 28%

L-cysteine methyl ester hydrochloride (18598-63-5) + Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1-oxide (52303-69-2, 108114-60-9, 108114-61-0) → isoprothiolane (50512-35-1) + 2-((R)-4-Methoxycarbonyl-thiazolidin-2-ylidene)-malonic acid diisopropyl ester

Conditions	Yield
With pyridine; acetic anhydride; triethylamine 1.) aq. MeOH, 1 h, room temperature, 2.) 23 h, room temperature; Yield given. Multistep reaction. Yields of byproduct given;

Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1-oxide (52303-69-2, 108114-60-9, 108114-61-0) → isoprothiolane (50512-35-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77 percent / methanol / 12 h / Ambient temperature 2: 47 percent / Na2CO3 / methanol; H2O / Ambient temperature View Scheme

C26H42O11S4 (147848-84-8) → isoprothiolane (50512-35-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 28 percent / Na2CO3 / methanol; H2O / 12 h / Ambient temperature 2: 64 percent / NaBH4 / methanol; tetrahydrofuran / 1.) 3 d, room temperature, 2.) 2 h, reflux View Scheme

isoprothiolane (50512-35-1) → 2-[1,3]Dithiolan-2-yl-malonic acid diisopropyl ester (106262-50-4)

Conditions	Yield
With magnesium In methanol at 10℃; for 2.5h;	93%

isoprothiolane (50512-35-1) → 1,3-dithiolan-2-ylidenemalonic acid (52322-05-1)

Conditions	Yield
With sodium hydroxide; water In isopropyl alcohol at 30 - 40℃; for 3h;	85%

isoprothiolane (50512-35-1) → anti-Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1,3-dioxide (133188-15-5, 147848-83-7)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 1h; Ambient temperature;	70%

isoprothiolane (50512-35-1) → Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1-oxide (52303-69-2, 108114-60-9, 108114-61-0)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 2h; Ambient temperature;	65%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 12h; Ambient temperature;	65%

isoprothiolane (50512-35-1) → 2-(1,3-dithiolan-2-ylidene)-3-isopropoxy-3-oxopropionic acid

Conditions	Yield
With sodium hydroxide In methanol; water at 25 - 45℃;	55%
With potassium hydroxide
With potassium hydroxide

methanol (67-56-1) + isoprothiolane (50512-35-1) → 3-Methoxy-1,1,4,4-tetraoxo-1λ6,4λ6-[1,4]dithiane-2,2-dicarboxylic acid diisopropyl ester

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid 1.) CH2Cl2, 12 h, room temperature, 2.) 3 d; Yield given. Multistep reaction;

isoprothiolane (50512-35-1) → 2-(1,3-dithiolan-2-ylidene)acetic acid (72629-81-3) + oxalic acid (144-62-7) + 3,5-bis-1,2,4-trithiolane (72629-83-5) + 1,3-dithiolan-2-ylidenemalonic acid (52322-05-1) + 2,4-bis-1,3-dithietane

Conditions	Yield
With silica gel for 2.5h; Product distribution; Irradiation; effects of surface and air on pesticide photolysis, different time; different λ; furter pesticides;

isoprothiolane (50512-35-1) → 2,2-dimethyl-5-5(2,5-dithiacyclopentylidene)-1,3-dioxane-4,6-dione (109480-62-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 5-[1,3]Dithiolan-2-ylidene-2-ethyl-2-methyl-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 8-[1,3]Dithiolan-2-ylidene-6,10-dioxa-spiro[4.5]decane-7,9-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 3-[1,3]Dithiolan-2-ylidene-1,5-dioxa-spiro[5.5]undecane-2,4-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 2-methyl-2-phenyl-5-(1,3-dithiolan-2-ylidene)-1,3-dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 5-[1,3]Dithiolan-2-ylidene-2-furan-2-yl-2-methyl-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 5-[1,3]Dithiolan-2-ylidene-2-ethyl-2-phenyl-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 3-(5-[1,3]Dithiolan-2-ylidene-2-methyl-4,6-dioxo-[1,3]dioxan-2-yl)-propionic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → Diisopropyl 1,3-dioxo-1,3-dithiolan-2-ylidenemalonate

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / m-chloroperbenzoic acid (MCPBA) / CH2Cl2 / 12 h / Ambient temperature 2: m-chloroperbenzoic acid (MCPBA) / CH2Cl2 / 12 h / Ambient temperature View Scheme

isoprothiolane (50512-35-1) → 2-(2-Chloro-phenyl)-5-[1,3]dithiolan-2-ylidene-2-methyl-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 2,2-Dicyclopentyl-5-[1,3]dithiolan-2-ylidene-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 2-((R)-4-Methoxycarbonyl-thiazolidin-2-ylidene)-malonic acid diisopropyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / m-chloroperbenzoic acid (MCPBA) / CH2Cl2 / 12 h / Ambient temperature 2: 2.) Ac2O, pyridine, NEt3 / 1.) aq. MeOH, 1 h, room temperature, 2.) 23 h, room temperature View Scheme

isoprothiolane (50512-35-1) → 5-[1,3]Dithiolan-2-ylidene-2,2-diphenyl-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 3-Ethylsulfanyl-1,4-dioxo-1λ4,4λ4-[1,4]dithiane-2,2-dicarboxylic acid diisopropyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / m-chloroperbenzoic acid (MCPBA) / CH2Cl2 / 12 h / Ambient temperature 2: 1.) metachloroperbenzoic acid (MCPBA) / 1.) CH2Cl2, 12 h, room temperature, 2.) MeOH, 2 d, room temperature View Scheme

isoprothiolane (50512-35-1) → 2-(4-Allyloxy-phenyl)-5-[1,3]dithiolan-2-ylidene-2-ethyl-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 5-[1,3]Dithiolan-2-ylidene-2-methyl-2-(2-prop-2-ynyloxy-phenyl)-[1,3]dioxane-4,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium hydroxide, water / propan-2-ol / 3 h / 30 - 40 °C 2: 1.) conc. sulfuric acid, acetic anhydride / 1.) 10 min, 2.) RT, 8 h View Scheme

isoprothiolane (50512-35-1) → 2-[(2-Benzyldisulfanyl-ethylsulfanyl)-benzylsulfanyl-methylene]-malonic acid diisopropyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / m-chloroperbenzoic acid (MCPBA) / CH2Cl2 / 12 h / Ambient temperature 2: 94 percent / methanol / Ambient temperature View Scheme

Upstream product

• 147848-84-8 C₂₆H₄₂O₁₁S₄ 
• 52303-69-2 Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1-oxide 
• 147848-85-9 3-{2-[2-(2,2-Bis-isopropoxycarbonyl-1-methoxy-vinylsulfanyl)-ethyldisulfanyl]-ethylsulfanyl}-2-isopropoxycarbonyl-3-methoxy-acrylic acid isopropyl ester 
• 147848-87-1 2-[(2-Ethyldisulfanyl-ethylsulfanyl)-ethylsulfanyl-methylene]-malonic acid diisopropyl ester 
• 18598-63-5 L-cysteine methyl ester hydrochloride 
• 67-56-1 methanol 

Downstream Products

• 52303-69-2 Diisopropyl 1,3-dithiolan-2-ylidenemalonate 1-oxide 
• 72629-81-3 2-(1,3-dithiolan-2-ylidene)acetic acid 
• 144-62-7 oxalic acid 
• 72629-83-5 3,5-bis-1,2,4-trithiolane 
• 52322-05-1 1,3-dithiolan-2-ylidenemalonic acid 

Relevant articles and documents

Synergistic Combinations Of Active Ingredients

The present invention relates to novel active compound combinations comprising, firstly, at least one known compound of the formula (I) in which R1 and A have the meanings given in the description and, secondly, at least one further known active compound from groups (2) to (27) listed in the description, which combinations are highly suitable for controlling animal pests such as insects and unwanted acarids and also phytopathogenic fungi.

Chemical Reactivity of Oxidation Products of the Dithiolanylidenemalonate Fungicide, Isoprothiolane

Diisopropyl dithiolanylidenemalonate (isoprothiolane) was oxidized with m-chloroperbenzoic acid to give a monosulfoxide, disulfoxide, and disulfone.The monosulfide was subjected to addition reactions with such nucleophiles as methanol, thiols, and amines at the thioacetal carbon to open the dithiolane ring, affording a thiosulfinate, sulfinate and disulfide.The presence of a small amount of sodium carbonate accelerated the reactions and, moreover, reformed isoprothiolane from the ring-opened addition products.The further oxidation products were transformed into dithianes by reacting with nucleophiles.Isoprothiolane monosulfoxide inhibited alcohol dehydrogenase, an SH enzyme.