# Thiocarbamate

A **thiocarbamate** is an organic compound in which sulfur is attached either to the carbonyl carbon, giving a –CS– (thiocarbonyl) group, or in place of the carbamate's alkoxy oxygen.<sup>[1](https://www.ncbi.nlm.nih.gov/mesh/D02.241.081.251.869)</sup><sup> • </sup><sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0277538709000370)</sup> The name covers two tautomeric families with the general formulas R¹SC(O)NR²R³, in which the organic group R± sits on sulfur (S-thiocarbamates), and R±OC(S)NR²R³, in which it sits on oxygen (O-thiocarbamates); R² and R³ may be hydrogen, alkyl, or one alkyl and one cyclic group.<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0277538709000370)</sup> Replacing the carbonyl oxygen of a carbamate with sulfur gives a thiocarbamate, and replacing the alkoxy oxygen as well gives a dithiocarbamate.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7968508/)</sup> The class matters in three areas: as synthetic intermediates, most prominently in the [Newman–Kwart rearrangement](https://www.edgepedia.org/newman-kwart-rearrangement) that converts phenols to thiophenols; as agricultural chemicals, since several thiocarbamate herbicides are in wide use; and in biomedicine, where related compounds include the alcohol-deterrent drug disulfiram.<sup>[4](https://www.sciencedirect.com/science/article/pii/S0040403925002394)</sup><sup> • </sup><sup>[5](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=300051QF.TXT)</sup><sup> • </sup><sup>[6](https://pubchem.ncbi.nlm.nih.gov/compound/antabuse)</sup>

| Key fact | Detail |
|---|---|
| Definition | Thiocarbamates include derivatives in which either the carbonyl oxygen (O-thiocarbamates) or the alkoxy oxygen (S-thiocarbamates) is replaced by sulfur<sup>[1](https://www.ncbi.nlm.nih.gov/mesh/D02.241.081.251.869)</sup><sup> • </sup><sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0277538709000370)</sup> |
| Isomeric forms | S-thiocarbamates R¹SC(O)NR²R³ and O-thiocarbamates R¹OC(S)NR²R³; dithiocarbamates replace both oxygens with sulfur<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0277538709000370)</sup><sup> • </sup><sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7968508/)</sup> |
| Named reaction | The Newman–Kwart rearrangement converts O-aryl thiocarbamates to S-aryl thiocarbamates on heating, a key step in making thiophenols from phenols<sup>[4](https://www.sciencedirect.com/science/article/pii/S0040403925002394)</sup> |
| Herbicides | EPTC, butylate, cycloate, diallate, ethiolate, molinate, pebulate, triallate, and vernolate are thiocarbamate herbicides<sup>[5](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=300051QF.TXT)</sup> |
| Mode of action | Thiocarbamate herbicides inhibit very-long-chain fatty acid (VLCFA) synthesis; the oxidized metabolites of thiobencarb, its sulfoxide and sulfone, inhibit VLCFA elongase<sup>[7](https://www.jstage.jst.go.jp/article/jpestics/37/4/37_D12-999/_html/-char/en)</sup> |
| Environmental fate | EPTC dissipates in soil with a field half-life of 2 to 18.8 days (mean 8.6 days) and is highly volatile<sup>[8](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1009KIB.TXT)</sup> |
| Toxicological note | A disulfiram-like reaction (flushing, sweating, headache, tachycardia, hypotension) may follow ethanol ingestion after large thiocarbamate exposure<sup>[9](https://cdn.who.int/media/docs/default-source/chemical-safety/intox/soundmanagementpesticides_resourcetool.pdf)</sup> |

## Structure and isomerism

The thiocarbamate group exists in two connectively distinct forms. In the S-thiocarbamate the organic group is bonded to sulfur, R¹SC(O)NR²R³; in the O-thiocarbamate it is bonded to oxygen, R¹OC(S)NR²R³. The two are described as tautomeric species under the generic name, and both are well known as substance classes in their own right.<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0277538709000370)</sup><sup> • </sup><sup>[10](https://www.sciencedirect.com/org/science/article/pii/S1434193X22056183)</sup> The distinction matters synthetically: O-aryl thiocarbamates are the starting materials for the Newman–Kwart rearrangement, while S-organyl thiocarbamates include the herbicides thiobencarb, [orbencarb](https://www.edgepedia.org/orbencarb), and molinate.<sup>[4](https://www.sciencedirect.com/science/article/pii/S0040403925002394)</sup><sup> • </sup><sup>[10](https://www.sciencedirect.com/org/science/article/pii/S1434193X22056183)</sup>

Like carbamates, thiocarbamates are heteroatom-rich, and this structure underlies their spread of uses. A 2026 review describes them as having broad application prospects in organic synthesis, analytical chemistry, materials science, and biomedicine.<sup>[11](https://pubs.rsc.org/en/content/articlelanding/2026/ob/d6ob00255b)</sup> O-thiocarbamates have also been used as hydrogen sulfide (H₂S) donors in biological systems and as intermediates in pharmaceutically significant syntheses.<sup>[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC6633899/)</sup>

## Synthesis

A 1967 review by Walter and colleagues organized thiocarbamate preparation into six method families: addition of alcohols and thiols to isothiocyanates; thioacylation of amines with chlorothioformates, O,S-diesters of dithiocarbonic acid, or trithiocarbonates; thioacylation of alcohols, phenols, and thiols with thiocarbamoyl chlorides, N,N-dialkylmercaptochloroformimidium chlorides, or N,N′-thiocarbonyldiimidazole; reaction of thiocyanates and cyanates with hydrogen sulfide; alkylation of metal dithiocarbamates; and additions to thiocyanic acid.<sup>[13](https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.196702811)</sup> Simple examples such as N,S-diethyl thiocarbamate are obtained from the appropriate amine and ethyl chlorothioformate.<sup>[14](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/thiocarbamate)</sup>

**Newer methods reduce hazardous reagents.** Traditional routes rely on halogenated precursors such as thiophosgene, thiocarbamoyl chlorides, and chlorothionoformates.<sup>[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC6633899/)</sup> Greener alternatives include addition of amines to [potassium thiocyanate](https://www.edgepedia.org/potassium-thiocyanate) or isothiocyanates, and a catalyst-free three-component reaction of elemental sulfur, isocyanides, and alcohols or thiols that gives O-thiocarbamates and dithiocarbamates directly.<sup>[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC6633899/)</sup> A one-pot isocyanide-based protocol converts N-formamides to S-thiocarbamates by dehydration with p-toluenesulfonyl chloride followed by addition of a sulfoxide component, without isolating the isocyanide intermediate; it was used to make a library of sixteen S-thiocarbamates and four norbornene-based monomers for [ring-opening metathesis](https://www.edgepedia.org/ring-opening-metathesis) polymerization.<sup>[10](https://www.sciencedirect.com/org/science/article/pii/S1434193X22056183)</sup> Recent reviews also record photochemical and electrochemical strategies for making the class.<sup>[11](https://pubs.rsc.org/en/content/articlelanding/2026/ob/d6ob00255b)</sup>

## The Newman–Kwart rearrangement

The Newman–Kwart rearrangement, developed independently by Melvin S. Newman and Har Kwart in the 1960s, is the best-known reaction of O-aryl thiocarbamates: on heating, the aryl group migrates from oxygen to sulfur, converting an O-aryl thiocarbamate into the corresponding S-aryl thiocarbamate.<sup>[4](https://www.sciencedirect.com/science/article/pii/S0040403925002394)</sup> [Hydrolysis](https://www.edgepedia.org/hydrolysis) of the S-aryl product then releases the thiophenol, so the sequence phenol → O-aryl thiocarbamate → S-aryl thiocarbamate → thiophenol is a general route from phenols to thiophenols.<sup>[15](https://www.orgsyn.org/Content/pdfs/procedures/CV6P0824.pdf)</sup> The reaction has been applied from large-scale industrial processes to the synthesis of ligands and supramolecular structures.<sup>[16](https://www.research.ed.ac.uk/en/publications/mechanism-and-application-of-the-newman-kwart-o-gt-s-rearrangemen/)</sup>

Its major limitation is the high temperature the uncatalyzed thermal rearrangement requires. Recent catalytic work has attacked this directly. A palladium-catalyzed method developed by Lloyd-Jones and colleagues lowered the reaction temperature to around 100 °C by proceeding through oxidative addition of the C–O bond of the O-aryl thiocarbamate. A single-electron oxidation approach introduced by Nicewicz and colleagues, based on electrophilic thiyl radical intermediates, allowed the rearrangement at room temperature and expanded the substrate scope; it was extended to cerium and iron oxidants and to electrochemical protocols. A bismuth catalyst system has since been developed for O-heteroaryl thiocarbamates at room temperature.<sup>[4](https://www.sciencedirect.com/science/article/pii/S0040403925002394)</sup>

## Thiocarbamate herbicides

A number of S-alkyl thiocarbamates are used as herbicides. The list includes butylate, cycloate, diallate, ethiolate, EPTC, molinate, pebulate, triallate, and [vernolate](https://www.edgepedia.org/vernolate).<sup>[5](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=300051QF.TXT)</sup> EPTC (S-ethyl dipropylthiocarbamate), sold as Eptam, was registered in the United States in 1958 as a selective preemergent herbicide, originally owned by Stauffer Chemical Company.<sup>[17](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=20000SBW.TXT)</sup> Thiobencarb, S-(4-chlorobenzyl)-N,N-diethylthiocarbamate, is used on rice, wheat, corn, and soybean at application rates of 1.5 to 7.5 kg active ingredient per hectare, with strong selectivity for rice.<sup>[7](https://www.jstage.jst.go.jp/article/jpestics/37/4/37_D12-999/_html/-char/en)</sup>

**Mode of action.** The thiocarbamate herbicides inhibit the biosynthesis of very-long-chain fatty acids (VLCFAs), fatty acids of 20 or more carbons whose elongation is catalyzed by VLCFA elongases.<sup>[7](https://www.jstage.jst.go.jp/article/jpestics/37/4/37_D12-999/_html/-char/en)</sup><sup> • </sup><sup>[18](https://www.cambridge.org/core/journals/weed-technology/article/very-long-chain-fatty-acidinhibiting-herbicides-current-uses-site-of-action-herbicideresistant-weeds-and-future/9BE1EFACFCDD5BC64B8A0461D9C9FEA6)</sup> In thiobencarb the parent compound only slightly inhibits the elongase; the active forms are its oxidized metabolites, the sulfoxide and sulfone, which inhibit VLCFA elongase in microsomal fractions of barnyard millet seedlings.<sup>[7](https://www.jstage.jst.go.jp/article/jpestics/37/4/37_D12-999/_html/-char/en)</sup> Under the Herbicide Resistance Action Committee (HRAC) classification, the thiocarbamates were long placed in group N (inhibition of lipid synthesis other than ACCase); in a 2020 update most group N active ingredients were moved into group 15 (K3), inhibition of VLCFA synthesis, and class N was deleted.<sup>[19](https://hracglobal.com/who-we-are/working-groups/group-15-vlcfa-inhibitors-resistance)</sup>

**Field behavior.** These herbicides are volatile and nonpersistent. Thiocarbamates generally disappear from soil within 1 to 4 weeks through microbial action, hydrolysis, vaporization, and leaching.<sup>[5](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=300051QF.TXT)</sup> For EPTC specifically, terrestrial field dissipation half-lives range from 2 to 18.8 days with a mean of 8.6 days; the compound is highly volatile, with a vapor pressure of 1.60 × 10⁻² mm Hg at 20 °C, and must be incorporated into soil shortly after application to avoid volatilization and photodegradation losses.<sup>[8](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1009KIB.TXT)</sup><sup> • </sup><sup>[20](https://cals.cornell.edu/weed-science/herbicides/herbicide-reference/eptam-eptc)</sup> Because volatility and microbial degradation occur concurrently, the primary environmental fate of EPTC is difficult to distinguish.<sup>[8](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1009KIB.TXT)</sup>

## Toxicology and crop protection

The EPA derived a reference dose of 0.025 mg/kg/day for EPTC.<sup>[21](https://www.epa.gov/sites/default/files/2014-09/documents/chapter_8_eptc.pdf)</sup> When a person drinks ethanol after being exposed to large quantities of thiocarbamates, a disulfiram-like reaction can occur, producing symptoms such as facial flushing, perspiration, head pain, fatigue, rapid heartbeat, and low blood pressure.<sup>[9](https://cdn.who.int/media/docs/default-source/chemical-safety/intox/soundmanagementpesticides_resourcetool.pdf)</sup> This parallels the chemistry of disulfiram itself, a dithiocarbamate whose inhibition of aldehyde dehydrogenase underlies its use as an alcohol-aversion drug.<sup>[22](https://archive.epa.gov/scipoly/sap/meetings/web/pdf/thio_final.pdf)</sup>

In crops, thiocarbamate injury is managed with [herbicide safeners](https://www.edgepedia.org/herbicide-safener), compounds that selectively enhance herbicide detoxification in crop plants. Safener dichlormid was shown in 1979 to protect corn from injury by the thiocarbamate EPTC, and a documented safener mechanism is the glutathione-mediated conjugation of thiocarbamate sulfoxides, catalyzed by glutathione S-transferases.<sup>[23](https://www.mdpi.com/2073-4395/12/11/2824)</sup><sup> • </sup><sup>[24](https://onlinelibrary.wiley.com/doi/full/10.1111/j.1399-3054.1994.tb02985.x)</sup>

## References

1. [Thiocarbamates, MeSH, National Library of Medicine](https://www.ncbi.nlm.nih.gov/mesh/D02.241.081.251.869)
2. [N–H⋯SC hydrogen bond in O-alkyl N-methoxycarbonyl thiocarbamates, Journal of Molecular Structure](https://www.sciencedirect.com/science/article/abs/pii/S0277538709000370)
3. [Carbamate Group as Structural Motif in Drugs, Biomolecules (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7968508/)
4. [Recent advances in the Newman–Kwart rearrangement, Tetrahedron Letters](https://www.sciencedirect.com/science/article/pii/S0040403925002394)
5. [Guidelines for the Disposal of Small Quantities of Unused Pesticides, US EPA](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=300051QF.TXT)
6. [Disulfiram, PubChem](https://pubchem.ncbi.nlm.nih.gov/compound/antabuse)
7. [Action mechanism of a herbicide, thiobencarb, Journal of Pesticide Science](https://www.jstage.jst.go.jp/article/jpestics/37/4/37_D12-999/_html/-char/en)
8. [Health Effects Support Document for S-Ethyl dipropylthiocarbamate (EPTC), US EPA, January 2008](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1009KIB.TXT)
9. [IPCS, Sound Management of Pesticides resource tool, WHO](https://cdn.who.int/media/docs/default-source/chemical-safety/intox/soundmanagementpesticides_resourcetool.pdf)
10. [One-Pot Synthesis of Thiocarbamates, European Journal of Organic Chemistry](https://www.sciencedirect.com/org/science/article/pii/S1434193X22056183)
11. [Recent progress on thiocarbamates: synthesis and applications, Organic & Biomolecular Chemistry](https://pubs.rsc.org/en/content/articlelanding/2026/ob/d6ob00255b)
12. [A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6633899/)
13. [Syntheses of Thiocarbamates, Angewandte Chemie International Edition (1967)](https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.196702811)
14. [Thiocarbamate – an overview, ScienceDirect Topics](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/thiocarbamate)
15. [2-Naphthalenethiol procedure, Organic Syntheses](https://www.orgsyn.org/Content/pdfs/procedures/CV6P0824.pdf)
16. [Mechanism and application of the Newman–Kwart O → S rearrangement, University of Edinburgh](https://www.research.ed.ac.uk/en/publications/mechanism-and-application-of-the-newman-kwart-o-gt-s-rearrangemen/)
17. [Reregistration Eligibility Decision: EPTC, US EPA](https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=20000SBW.TXT)
18. [Very long chain fatty acid–inhibiting herbicides, Weed Technology](https://www.cambridge.org/core/journals/weed-technology/article/very-long-chain-fatty-acidinhibiting-herbicides-current-uses-site-of-action-herbicideresistant-weeds-and-future/9BE1EFACFCDD5BC64B8A0461D9C9FEA6)
19. [Group 15 – VLCFA-inhibitor Resistance, HRAC](https://hracglobal.com/who-we-are/working-groups/group-15-vlcfa-inhibitors-resistance)
20. [Eptam / EPTC herbicide reference, Cornell CALS](https://cals.cornell.edu/weed-science/herbicides/herbicide-reference/eptam-eptc)
21. [EPA OGWDW Chapter 8: EPTC](https://www.epa.gov/sites/default/files/2014-09/documents/chapter_8_eptc.pdf)
22. [Thiocarbamates: Screening Level Cumulative Dietary Risk Assessment, US EPA](https://archive.epa.gov/scipoly/sap/meetings/web/pdf/thio_final.pdf)
23. [Current Advances in the Action Mechanisms of Safeners, Agronomy](https://www.mdpi.com/2073-4395/12/11/2824)
24. [Herbicide safeners and glutathione metabolism, Physiologia Plantarum](https://onlinelibrary.wiley.com/doi/full/10.1111/j.1399-3054.1994.tb02985.x)

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*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Carbonyl and carboxyl chemistry › Carboxylic acid derivatives › Carbonate esters, orthoesters, and carbamates › Thiocarbamates and dithiocarbamates*

*Initially written Sep 17, 2026 · Reviewed: Oct 15, 2026 · Edited: Oct 11, 2026; Oct 15, 2026 · Last review: Oct 15, 2026*

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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license