2212-67-1

Basic information

• Product Name: Molinate
• Synonyms: Felan;hexahydro-1h-azepine-1-carbothioicacis-ethylester;higalnate;Jalan;malerbanegiavonil;molinateestrella;Molmate;ordam
• CAS NO: 2212-67-1
• Molecular Formula: C₉H₁₇NOS
• Molecular Weight: 187.3
• EINECS: 218-661-0
• Product Categories: ThiocarbamatesMethod Specific;2005/48/EU;Alphabetic;European Community: ISO and DIN;Herbicides;M;METI - MZPesticides&Metabolites;Alpha sort;H-MAlphabetic;Pesticides&Metabolites
• Mol File: 2212-67-1.mol

Chemical Properties

• Melting Point: <25 °C
• Boiling Point: 202°C (10 mmHg)
• Flash Point: 100 °C
• Appearance: Amber/Liquid
• Density: 1.06
• Vapor Pressure: 0.00412mmHg at 25°C
• Refractive Index: 1.5250 (estimate)
• Storage Temp.: 0-6°C
• PKA: -1.22±0.20(Predicted)
• Water Solubility: 0.08 g/100 mL
• BRN: 1239196
• CAS DataBase Reference: Molinate(CAS DataBase Reference)
• NIST Chemistry Reference: Molinate(2212-67-1)
• EPA Substance Registry System: Molinate(2212-67-1)

Safety Data

• Hazard Codes: T,N,Xn
• Statements: 20/22-40-43-48/22-63-50/53-62
• Safety Statements: 36/37-46-60-61
• RIDADR: 2902
• WGK Germany: 3
• RTECS: CM2625000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 2212-67-1(Hazardous Substances Data)

Usage

Uses

Used in Agricultural Industry:
Molinate is used as a selective herbicide for the control of water grass and other weeds in rice crops. It helps to maintain the health and productivity of rice fields by targeting and eliminating unwanted plant growth.

Reactivity Profile

Molinate is a thiocarbamate. Flammable gases are generated by the combination of thiocarbamates and dithiocarbamates with aldehydes, nitrides, and hydrides. Thiocarbamates and dithiocarbamates are incompatible with acids, peroxides, and acid halides.

Trade name

ARROSOLO?; FELAN?; HIGALNATE?; HYDRAM?; JALAN?; MALERBANE-GIAVONI-L?;ORDAM?; ORDRAM?; R-4572?; RICECO; SAKKIMOL?; STAUFFER R 4,572?; YALAN?; YULAN?

Environmental Fate

Soil. Hydrolyzes in soil forming ethyl mercaptan, carbon dioxide and dialkylamine (half-life approximately 2–5 weeks) (Hartley and Kidd, 1987). At recommended rates of application, the half-life of molinate in moist loam soils at 21–27°C is approximately 3 weeks (Humburg et al., 1989). Rajagopal et al. (1989) reported that under flooded conditions, molinate was hydroxylated at the 3- and 4-position with subsequent oxidation forming many compounds including molinate sulfoxide, carboxymethyl molinate, hexahydroazepine- 1-carbothioate, 4-hydroxymolinate, 4-hydroxymolinate sulfoxide, hexahydroazepine, S-methyl hexahydroazepine-1-carbothioate, 4-ketomolinate, 4-hydroxyhexahydroazepine, 4-hydroxy-N-acetyl-hexahydroazepine, carbon dioxide and bound residues.Plant. Molinate is rapidly metabolized by plants releasing carbon dioxide and naturally occurring plant constituents (Humburg et al., 1989).Photolytic. Molinate in a hydrogen peroxide solution (120 mM) was irradiated by UV light (l = 290 nm) at 23°C. The major photooxidation products were the two isomers of 2-oxomolinate (20% yield) and s-molinate oxide (5% yield) (Draper and Crosby, 1984).Half-lives of 180 and 120 hours were observed using one and two equivalents of hydrogen peroxide, respectively (Draper and Crosby, 1984). Molinate has a UV absorption maximum at 225 nm and no absorption at wavelengths >290 nm. Therefore, molinate is not expected to undergo aqueous photolysis under natural sunlight (l = 290 nm). In the presence of tryptophan, a naturally occurring photosensitizer, molinate in aqueous solution photodegraded to form 1-((ethylsulfinyl)carbonyl)hexahydro-1H-azepine, S-ethyl hexahydro-2- oxo-1H-azepine-1-carbothioate and hexamethyleneimine (Soderquist et al., 1977).Chemical/Physical. Metabolites identified in tap water were molinate sulfoxide, 3- and 4-hydroxymolinate, ketohexamethyleneimine and 4-ketomolinate (Verschueren, 1983).

Metabolic pathway

Juvenile white sturgeon and common carp are exposed to 14C-molinate in a flow-through metabolism system and oxidize molinate to form several products and hydrolyze or conjugate with glutathione (GSH), the sulfoxide, or sulfone. Both fish form a D-glucuronic acid conjugate. The higher toxicity of molinate in common carp may be due to greater bioconcentration, slower depuration, and less efficient metabolic deactivation. In the blood of common carp, molinate is oxidized by erythrocytes to the sulfoxide and possibly the sulfone, then conjugated with GSH or cysteine and cleaved to form mercapturic acid in both erythrocytes and plasma. Conjugation and possible hemoglobin carbamylation occur only after sulfoxidation of molinate. Molinate is distributed uniformly throughout the soil layers, and its degradation products are identified as 2-oxomolinate, 4-oxomolinate, molinate acid, and hexamethyleneimine. In rice plants, 4-hydroxymolinate, 2-oxomolinate, 4-oxomolinate, S-ethyl-N-carboxymethylthiocarbamate, molinate acid, and molinate alcohol are detected. By the soil microorganisms, oxidation of the S-ethyl moiety is considered to be the main pathway, and hydroxy and oxoderivatives on the azepine ring are identified.

InChI:InChI=1/C9H17NOS/c1-2-12-9(11)10-7-5-3-4-6-8-10/h2-8H2,1H3

Upstream product

• 111-49-9 hexamethylene imine 
• 101506-43-8 O-(1-chloroethyl) S-ethyl carbonothioate 
• 75-00-3 chloroethane 
• 463-58-1 carbon oxide sulfide 
• 75-03-6 ethyl iodide 
• 201230-82-2 carbon monoxide 
• 64-67-5 diethyl sulfate 
• 56525-84-9 O-ethyl N,N-hexamethylene-thiocarbamate 

Downstream Products

• 54404-54-5 S-ethyl hexahydro-1H-azepine-1-carbothioate S,S-dioxide 
• 93-58-3 benzoic acid methyl ester 

Relevant articles and documents

Metathetic sulfur transfer mediated by N-(2-aminophenyl)-4-methyl-thiazolin-2-thione derivatives: a route to diversely substituted S-alkylcarbamothioates

A new route to S-alkylcarbamothioates is disclosed. In a first step, N-(2-aminophenyl)-4-methyl-thiazolin-2-thione is transformed into a mono- or disubstituted urea at nitrogen, and then in a second step, alkylated at sulfur. The resulting salts, after treatment with a base, gave S-alkylcarbamothioates in high isolated yields together with 3-methyl[1,3]thiazolo[3,2-a]benzimidazole under very mild conditions.

Solvent-assisted thiocarboxylation of amines and alcohols with carbon monoxide and sulfur under mild conditions

DMSO or DMF as a solvent strongly accelerated the thiocarboxylation of amines and alcohols with carbon monoxide and sulfur. Under mild conditions (1 atm, 20°C), this thiocarboxylation of amines assisted by DMSO with carbon monoxide and sulfur has been developed into a practical and convenient synthetic method for S-alkyl thiocarbamates in good to excellent yields, including EPTC, thiobencarb, orbencarb, and molinate (herbicides). DMF also showed the similar solvent effect. NMP slightly decreased the effect for the thiocarboxylation of amines, and the yield of S-alkyl thiocarbamate was lowered in DMAc. Surprisingly, no formation of S-alkyl thiocarbamate was observed at the use of the other solvents, such as THF, hexane, toluene, AcOEt, MeCN, MeOH, and H 2O. The present solvent-assisted thiocarboxylation with carbon monoxide and sulfur could be also applied to a new synthesis of S-alkyl O-alkyl carbonothioates from alcohols under mild conditions (1 atm, 20°C) in DMF using DBU (1,8-diazabicyclo[5.4.0]undec-7-ene).

Practical synthesis of S-alkyl thiocarbamate herbicides by carbonylation of amines with carbon monoxide and sulfur

An industrial and economic carbonylation of amines with carbon monoxide and sulfur has been developed for the synthesis of S-alkyl thiocarbamate herbicides. In the presence of potassium carbonate and solvent DMSO, S-alkyl thiocarbamates, such as thiobencarb and orbencarb (herbicides) are synthesized in excellent yields from amines, carbon monoxide, sulfur, and alkyl halides under mild conditions (1atm, 20°C).

Identification of a S-hexahydro-1H-azepine-1-carbonyl adduct produced by molinate on rat hemoglobin β2 and β3 chains in vivo

Molinate is a thiocarbamate herbicide used in the rice industry for over 25 years, and regulatory reports have shown that administration of molinate results in reproductive toxicity in male rats. Previous in vitro studies indicate that molinate undergoes oxidative metabolism, forming reactive electrophilic intermediates capable of undergoing nucleophilic addition by protein nucleophiles. On the basis of in vitro studies, carbamylation of an active site serine residue in Hydrolase A has been proposed to be the mechanism responsible for the observed testicular toxicity. The experiments presented here utilize hemoglobin to characterize covalent protein modifications produced in vivo by molinate. Rats were dosed intraperitoneally with molinate as a function of exposure duration. Examination of globin from molinate-treated rats by HPLC demonstrated a new peak in the isolated samples and, when collected and analyzed using MALDI-TOF MS, revealed a 126 Da increase in mass relative to the native β3 chain. Digestion of the globin using Glu-C and analysis by MALDI-TOF MS revealed two modified peptide fragments at m/z 2743 and 4985 consistent with a 126 Da increase to peptide fragments [122-146] and [102-146] in the unmodified β2 and β3 chains of globin. Using selected reaction monitoring LC/MS/MS, S-hexahydro-1H-azepine-1-carbonyl cysteine (HHAC-Cys) was identified in the globin hydrolysates isolated from the molinate-treated rats, but not in the control samples, and the quantity of adduct exhibited a cumulative dose response. These experiments demonstrate the ability of molinate to covalently modify proteins in vivo in a dose dependent manner. For hemoglobin this modification was a carbamylation at Cys-125 similar to the modification produced by disulfiram and N,N-diethyldithiocarbamate. The ability of molinate to covalently modify cysteine residues provides a potential mechanism to account for enzyme inhibition following molinate exposure and suggests that enzymes with cysteine residues in their active site may be inhibited by molinate.

Triazolecarboxamide herbicides

Compounds of the formula: STR1 wherein X is O or S; R and R1 are substituted or unsubstituted alkyl, alkenyl, alkynyl or cycloalkyl or R and R1 may be joined to form a heterocyclic ring; R2 is substituted or unsubstituted cycloalkyl; and n is 0, 1 or 2 are disclosed as well as their postemergence and preemergence selective herbicide use against both monocot and dicot weeds in crops such as sugarbeets, cotton, soybeans and rice.

Benzhydryl compounds as herbicide antidotes

Acids, esters, amides and salts of benzhydryl compounds are antidotes for thiocarbamate and acetamide herbicides. These antidote compounds are especially effective to safen acetamide herbicides used to control grassy weeds and broadleaf weeds in rice, sorghum, corn and wheat.

Synergistic composition and method for selective weed control in rice

Compositions that contain, in admixture with one another, as active ingredient, on the one hand N-[2-(2-methoxyethoxy)-phenylsulphonyl]-N'-(4,6-dimethoxy-1,3,5-triazin-2-yl)-urea of the formula STR1 and on the other hand one or two of the active ingredients of the formulae II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV and XV defined herein exhibit synergistic herbicidal action in rice.

Process for the preparation of carbamates, thiocarbamates and ureas

The invention relates to a process for preparing carbamic acid derivatives of formula: STR1 in which R1 or R2 denotes a hydrogen atom or a substituted or unsubstituted, saturated or unsaturated aliphatic, cycloaliphatic or heterocyclic radical, or R1 and R2 together form a ring, and Y denotes OR, SR, STR2 groups, R being a substituted or unsubstituted, saturated or unsaturated aliphatic or cycloaliphatic radical, or a substituted or unsubstituted aromatic radical, R3 and R4 denote a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical or together form a ring, and R6 and R7 denote a saturated or unsaturated, substituted or unsubstituted aliphatic or cycloaliphatic radical, a hydrogen atom, an alkylthio radical or an alkyloxy radical. According to the process, a compound of formula STR3 is reacted with an α-halogenated derivative of formula STR4 at a temperature of -5° to 150° C. in the presence of an acceptor for hydrohalic acid. The carbamates, thiocarbamates or ureas obtained are very useful, especially as pesticides.

The Synthesis of Alkyl Thiocarbamates in an Ultrasonic Field

The synthesis of alkylthiocarbamates from an alkali metal salt of thiocarbamic acid and halogenohydrocarbons in an aqueous medium has been investigated with exposure to ultrasound and without such exposure but under conditions of vigorous stirring.The intensifying effect of ultrasound on the synthesis thiocarbamates has been demonstrated.

Alkyl 1-Chloroalkyl Carbonates: Reagents for the Synthesis of Carbamates and Protection of Amino Groups

The synthesis of 1-chloroalkyl carbonates and their reaction with various type of amines are described.This reaction is useful for the synthesis of carbamate pesticides and for the protection of various amino groups, including amino acids.