{ "id": "epdt9y0q8e", "slug": "dithiane", "title": "Dithiane", "updated": "2026-10-15", "topic_path": [ { "id": "physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/topics/physical" }, { "id": "physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry" }, { "id": "physical.chemistry.organic", "label": "Organic substances", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic" }, { "id": "physical.chemistry.organic.alcohols_ethers_and_organooxygen", "label": "Alcohols, ethers, and organooxygen groups", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic.alcohols_ethers_and_organooxygen" }, { "id": "physical.chemistry.organic.alcohols_ethers_and_organooxygen.chalcogen_heavier_analogues", "label": "Organosulfur, selenium, and heavier main-group organo derivatives", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic.alcohols_ethers_and_organooxygen.chalcogen_heavier_analogues" }, { "id": "physical.chemistry.organic.alcohols_ethers_and_organooxygen.organosulfur_selenium", "label": "Organosulfur, selenium, and tellurium analogues", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic.alcohols_ethers_and_organooxygen.organosulfur_selenium" }, { "id": "physical.chemistry.organic.alcohols_ethers_and_organooxygen.sulfides_disulfides", "label": "Sulfides and disulfides", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic.alcohols_ethers_and_organooxygen.sulfides_disulfides" }, { "id": "physical.chemistry.organic.alcohols_ethers_and_organooxygen.sulfides_disulfides.medium_cyclic_sulfides", "label": "Five- and six-membered cyclic sulfides", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic.alcohols_ethers_and_organooxygen.sulfides_disulfides.medium_cyclic_sulfides" } ], "geo": [ { "id": "geo.us.t1946.physical.chemistry.organic.alcohols_ethers_and_organooxygen.chalcogen_heavier_analogues", "label": "United States · 1946 to 2000: Organosulfur, selenium, and heavier main-group organo derivatives", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.physical.chemistry.organic.alcohols_ethers_and_organooxygen.chalcogen_heavier_analogues", "path": [ { "id": "geo.us", "label": "United States", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us" }, { "id": "geo.us.t1946", "label": "United States · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946" }, { "id": "geo.us.t1946.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.physical" }, { "id": "geo.us.t1946.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.physical.chemistry" }, { "id": "geo.us.t1946.physical.chemistry.organic", "label": "Organic substances", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.physical.chemistry.organic" }, { "id": "geo.us.t1946.physical.chemistry.organic.alcohols_ethers_and_organooxygen", "label": "Alcohols, ethers, and organooxygen groups", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.physical.chemistry.organic.alcohols_ethers_and_organooxygen" }, { "id": "geo.us.t1946.physical.chemistry.organic.alcohols_ethers_and_organooxygen.chalcogen_heavier_analogues", "label": "Organosulfur, selenium, and heavier main-group organo derivatives", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.physical.chemistry.organic.alcohols_ethers_and_organooxygen.chalcogen_heavier_analogues" } ] } ], "excerpt": "Dithiane is a saturated six-membered heterocycle with two sulfur atoms and four carbon atoms; 1,3-dithiane, a cyclic thioacetal of formaldehyde, acts as a masked carbonyl group in umpolung synthesis.", "snippet": "Dithiane is a saturated six-membered heterocycle with two sulfur atoms and four carbon atoms; 1,3-dithiane, a cyclic thioacetal of formaldehyde, acts as a masked carbonyl group in umpolung synthesis.", "node": "physical.chemistry.organic.alcohols_ethers_and_organooxygen.sulfides_disulfides.medium_cyclic_sulfides", "markdown": "# Dithiane\n\n**Dithiane** is the name for saturated six-membered heterocycles containing two sulfur atoms and four carbon atoms; the most important member is **1,3-dithiane** (C₄H₈S₂, CAS 505-23-7), a cyclic thioacetal of formaldehyde that serves in organic synthesis as a masked carbonyl group and, after deprotonation, as an acyl anion equivalent[1](https://webbook.nist.gov/cgi/cbook.cgi?ID=505-23-7). Three positional isomers exist, 1,2-, 1,3-, and 1,4-dithiane, but the 1,3-isomer and its derivatives, called 1,3-dithianes, dominate the chemistry because of their role in polarity-inverted (umpolung) carbonyl synthesis[2](https://chem.libretexts.org/Ancillary_Materials/Reference/Organic_Chemistry_Glossary/Dithiane).\n\n| Key fact | Detail |\n|---|---|\n| Formula / mass | C₄H₈S₂, molecular weight 120.236; CAS Registry Number 505-23-7[1](https://webbook.nist.gov/cgi/cbook.cgi?ID=505-23-7) |\n| Other names | m-Dithiane; 1,3-dithiacyclohexane; dithiane-1,3[1](https://webbook.nist.gov/cgi/cbook.cgi?ID=505-23-7) |\n| Synthetic role | Cyclic thioacetal of formaldehyde; the 2-position can be deprotonated to give a 2-lithio-1,3-dithiane, an acyl anion equivalent[3](https://www.uwindsor.ca/people/jgreen/sites/uwindsor.ca.people.jgreen/files/tet-2003-59-6147-yus.pdf) |\n| Origin of the method | Corey and Seebach described the use of dithianes to access acyl anion equivalents from aldehydes in the 1960s[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8518712/) |\n| Chiral variant | trans-1,3-Dithiane-1,3-dioxide acts as a chiral acyl anion equivalent for enantioselective synthesis of α-hydroxy acid derivatives[5](https://pubs.rsc.org/en/content/articlelanding/1994/c3/c39940001653) |\n\n## Structure and properties\n\n1,3-Dithiane is a six-membered ring in which sulfur atoms occupy the 1 and 3 positions. The NIST Chemistry WebBook lists the formula C₄H₈S₂, molecular weight 120.236, and the InChIKey WQADWIOXOXRPLN-UHFFFAOYSA-N; condensed-phase thermochemistry, phase change, ion energetics, IR, mass, UV/visible, and gas chromatography data are available for the compound[1](https://webbook.nist.gov/cgi/cbook.cgi?ID=505-23-7). As a thioacetal it is stable to many conditions that would destroy a free aldehyde or ketone, which is the basis of its double use as a protecting group and as a reactivity-inverting reagent[6](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/thioacetal).\n\n## The umpolung principle\n\nA carbonyl carbon is electrophilic: the electronegativity of oxygen leaves the carbon partially positive, so it is normally attacked by nucleophiles. Umpolung, a term introduced by Corey and Seebach and popularized by Seebach, temporarily reverses this polarity so that the carbonyl carbon behaves as a nucleophile[7](https://www.sciencedirect.com/science/article/abs/pii/S0040402003009554) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8518712/). Converting an aldehyde to its 1,3-dithiane achieves this: the two sulfur atoms stabilize a carbanion at the carbon between them, and deprotonation with a strong base such as n-butyllithium gives 2-lithio-1,3-dithiane, which reacts with electrophiles and, after hydrolysis of the thioacetal, delivers a carbonyl compound with a new carbon-carbon bond[3](https://www.uwindsor.ca/people/jgreen/sites/uwindsor.ca.people.jgreen/files/tet-2003-59-6147-yus.pdf). The sulfur atoms are essential here; the oxygen analog is not viable because it does not stabilize the anion comparably[8](https://www.quimicaorganica.org/en/sulfur%2C-phosphorus%2C-and-silicon/1831-synthesis-of-1%2C3-dithianes-umpolung-reactions.html).\n\nThe anions of cyclic dithianes are more stable than those of noncyclic thioacetals, an advantage credited to Corey and Seebach[6](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/thioacetal). A second deprotonation and alkylation sequence on a monosubstituted dithiane extends the method to formaldehyde or methylene dianion equivalents, giving products that can be hydrolyzed or reduced further[3](https://www.uwindsor.ca/people/jgreen/sites/uwindsor.ca.people.jgreen/files/tet-2003-59-6147-yus.pdf).\n\n## Preparation and removal\n\n1,3-Dithianes are made by treating a carbonyl compound with 1,3-propanedithiol under [Lewis acid catalysis](https://www.edgepedia.org/lewis-acid-catalysis), for example with [boron trifluoride etherate](https://www.edgepedia.org/boron-trifluoride-etherate), to form the dithioacetal[9](https://www.epfl.ch/labs/lcso/wp-content/uploads/2018/06/StructureandReactivity-2010.pdf).\n\n## Applications in synthesis\n\nThe most important use of 1,3-dithianes stems from their ability to function as acyl anion equivalents: metallation, alkylation of the anion, and cleavage of the dithiane group produces a carbonyl compound[10](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/dithiane). Beyond simple alkylation, β-keto 1,3-dithianes serve as masked 1,3-dicarbonyl systems that can be converted into functionalized oxygen-containing heterocycles for natural product synthesis[11](https://pubs.rsc.org/en/content/articlehtml/2003/ob/b208982c).\n\n**Complex natural products.** Since the late 1970s, dithianes have featured prominently in the natural product synthesis program of [Amos B. Smith](https://www.edgepedia.org/amos-b-smith-iii), III, at the Monell Chemical Senses Center and the University of Pennsylvania, both for union of advanced fragments and for multicomponent linchpin couplings; Smith and Christopher M. Adams reviewed this evolution in *Accounts of Chemical Research* in 2004[12](https://pubs.acs.org/achre4/article/37/6/365/3453470/Evolution-of-Dithiane-Based-Strategies-for-the). A 2003 review in *Tetrahedron* surveyed total syntheses involving dithiane chemistry from 1990 onward, earlier reviews having covered the literature to 1990[7](https://www.sciencedirect.com/science/article/abs/pii/S0040402003009554).\n\n**Chiral dithiane dioxides.** Oxidation opens an asymmetric variant. trans-1,3-Dithiane-1,3-dioxide, reported by [Varinder K. Aggarwal](https://www.edgepedia.org/varinder-kumar-aggarwal) and coworkers at Oxford in 1994, reacts with high diastereoselectivity with aromatic aldehydes, and a Pummerer reaction converts the dithiane dioxide moiety to a thiolester without racemization; the thiolester is readily transformed into acids, esters, amides, ketones, and aldehydes[5](https://pubs.rsc.org/en/content/articlelanding/1994/c3/c39940001653). In the fuller 1997 study, (R,R)-(+)-1,3-dithiane-1,3-dioxide gave single diastereomers with benzaldehyde and 3,4-dimethoxybenzaldehyde in 84 and 76 percent purified yields, and the adducts became protected S-ethyl α-hydroxythioesters in 95 to 100 percent ee; the approach furnished the dimethyl ether of (R)-(−)-3,4-dihydroxymandelic acid in its naturally occurring form[13](https://www.sciencedirect.com/science/article/pii/S0040402097010107).\n\n**Related heterocycles.** The five-membered analogs, 1,3-dithiolanes, are familiar [carbonyl protecting groups](https://www.edgepedia.org/carbonyl-protecting-groups) but fragment at relatively low reaction temperatures, which limits their synthetic application to alkylation with highly reactive electrophiles[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC9907017/). A nitrogen-containing analog of 1,3-dithiane, 4,5-dihydro-5-methyl-1,3,5-dithiazine, provides a formaldehyde anion equivalent[10](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/dithiane). 1,3,5-Trithiane, the cyclic trimer of thioformaldehyde, is a second sulfur-based umpolung reagent that serves as a precursor to nucleophilic carbon species alongside 1,3-dithiane, though the two differ in their primary applications[15](https://pdf.benchchem.com/122/1_3_5_Trithiane_vs_1_3_Dithiane_A_Comparative_Guide_to_Umpolung_Chemistry.pdf).\n\n## Place among umpolung methods\n\nDithianes are one of three widely used approaches to acyl anion species from carbonyl compounds, alongside the cyanide-catalyzed benzoin reaction, known since 1832, and [N-heterocyclic carbene](https://www.edgepedia.org/n-heterocyclic-carbene) (NHC) catalysis[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8518712/). A practical limitation of dithiane umpolung reagents is that the molecule cannot carry acidic hydrogen atoms elsewhere, since these would be deprotonated along with the dithiane carbon; as the umpolung center is moved farther from the carbonyl, preparation of the requisite reagents also becomes more difficult[16](https://www.sciencedirect.com/topics/chemistry/umpolung). Within these limits, the general synthetic accessibility and reactivity of 1,3-dithianes have led to widespread application in fragment coupling and multicomponent linchpin strategies for architecturally complex targets[12](https://pubs.acs.org/achre4/article/37/6/365/3453470/Evolution-of-Dithiane-Based-Strategies-for-the).\n\n## References\n\n1. [1,3-Dithiane, NIST Chemistry WebBook, SRD 69](https://webbook.nist.gov/cgi/cbook.cgi?ID=505-23-7)\n2. [Dithiane, Chemistry LibreTexts Organic Chemistry Glossary](https://chem.libretexts.org/Ancillary_Materials/Reference/Organic_Chemistry_Glossary/Dithiane)\n3. [M. Yus, The role of 1,3-dithianes in natural product synthesis, Tetrahedron 59 (2003) 6147 (full text, University of Windsor)](https://www.uwindsor.ca/people/jgreen/sites/uwindsor.ca.people.jgreen/files/tet-2003-59-6147-yus.pdf)\n4. [S. Wang, B. König, Catalytic Generation of Carbanions through Carbonyl Umpolung, Angew. Chem. Int. Ed. 2021, 60, 21624](https://pmc.ncbi.nlm.nih.gov/articles/PMC8518712/)\n5. [V. K. Aggarwal, A. Thomas, R. J. Franklin, trans-1,3-Dithiane-1,3-dioxide, a new chiral acyl anion equivalent, J. Chem. Soc., Chem. Commun., 1994, 1653](https://pubs.rsc.org/en/content/articlelanding/1994/c3/c39940001653)\n6. [Thioacetal, ScienceDirect Topics overview](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/thioacetal)\n7. [The role of 1,3-dithianes in natural product synthesis, Tetrahedron (ScienceDirect abstract)](https://www.sciencedirect.com/science/article/abs/pii/S0040402003009554)\n8. [Synthesis of 1,3-dithianes. Umpolung reactions, quimicaorganica.org](https://www.quimicaorganica.org/en/sulfur%2C-phosphorus%2C-and-silicon/1831-synthesis-of-1%2C3-dithianes-umpolung-reactions.html)\n9. [Structure and Reactivity course notes, EPFL LCSO](https://www.epfl.ch/labs/lcso/wp-content/uploads/2018/06/StructureandReactivity-2010.pdf)\n10. [Dithiane, ScienceDirect Topics overview (Comprehensive Heterocyclic Chemistry chapter)](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/dithiane)\n11. [Development of β-keto 1,3-dithianes as versatile intermediates for organic synthesis, Org. Biomol. Chem., 2003](https://pubs.rsc.org/en/content/articlehtml/2003/ob/b208982c)\n12. [A. B. Smith, III, C. M. Adams, Evolution of Dithiane-Based Strategies for the Construction of Architecturally Complex Natural Products, Acc. Chem. Res. 2004, 37, 365–377](https://pubs.acs.org/achre4/article/37/6/365/3453470/Evolution-of-Dithiane-Based-Strategies-for-the)\n13. [trans-1,3-dithiane-1,3-dioxide; a chiral acyl anion equivalent, Tetrahedron 53 (1997) 16213](https://www.sciencedirect.com/science/article/pii/S0040402097010107)\n14. [1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9907017/)\n15. [1,3,5-Trithiane vs. 1,3-Dithiane: A Comparative Guide to Umpolung Chemistry, BenchChem](https://pdf.benchchem.com/122/1_3_5_Trithiane_vs_1_3_Dithiane_A_Comparative_Guide_to_Umpolung_Chemistry.pdf)\n16. [Umpolung, ScienceDirect Topics overview](https://www.sciencedirect.com/topics/chemistry/umpolung)\n\n---\n*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Alcohols, ethers, and organooxygen groups › Organosulfur, selenium, and heavier main-group organo derivatives › Organosulfur, selenium, and tellurium analogues › Sulfides and disulfides › Five- and six-membered cyclic sulfides*\n\n*Initially written Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/dithiane", "markdown_url": "https://www.edgepedia.org/dithiane.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Dithiane\", Edgepedia (EdgeChat), https://www.edgepedia.org/dithiane. Edgepedia Community License 1.0.", "credit_md": "\"[Dithiane](https://www.edgepedia.org/dithiane)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/dithiane](https://www.edgepedia.org/dithiane). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Dithiane\", Edgepedia (EdgeChat), https://www.edgepedia.org/dithiane. Edgepedia Community License 1.0.", "speakable": "Dithiane is a saturated six-membered heterocycle with two sulfur atoms and four carbon atoms; 1,3-dithiane, a cyclic thioacetal of formaldehyde, acts as a masked carbonyl group in umpolung synthesis." }