Symmetrical dimethylhydrazine

Symmetrical dimethylhydrazine
Names
Preferred IUPAC name
1,2-Dimethylhydrazine[2]
Other names
  • N,N'-Dimethylhydrazine[1]
  • sym-Dimethylhydrazine[1]
  • Hydrazomethane[1]
Identifiers
3D model (JSmol)
Abbreviations SDMH[1]
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.149.162
KEGG
MeSH 1,2-Dimethylhydrazine
RTECS number
  • MV2625000
UNII
UN number 2382
  • InChI=1S/C2H8N2/c1-3-4-2/h3-4H,1-2H3 Y
    Key: DIIIISSCIXVANO-UHFFFAOYSA-N Y
  • CNNC
Properties[3]
C2H8N2
Molar mass 60.100 g·mol−1
Appearance Colourless liquid
Odor Fishy, ammoniacal
Density 827.4 kg m−3 (at 20 °C)
Melting point −9 °C (16 °F; 264 K)
Boiling point 87 °C; 188 °F; 360 K
Miscible
Thermochemistry
171.04 J K−1 mol−1
199.15 J K−1 mol−1
−1987–−1978 kJ mol−1
Hazards
GHS labelling:[4]
Danger
H301, H311, H331, H350, H411
P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P310, P302+P352, P304+P340, P308+P313, P311, P312, P322, P330, P361, P363, P391, P403+P233, P405
Related compounds
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Symmetrical dimethylhydrazine (SDMH), or 1,2-dimethylhydrazine, is the organic compound with the formula (CH3NH)2. It is one of the two isomers of dimethylhydrazine. Both isomers are colourless liquids at room temperature, with properties like those of methylamines.[5] Symmetrical dimethylhydrazine is a potent carcinogen that acts as a DNA methylating agent.[6] The compound has no commercial value, in contrast to its isomer unsymmetrical dimethylhydrazine(1,1-dimethylhydrazine, UDMH), which is used as a rocket fuel.[7] SDMH is more toxic than unsymmetrical dimethylhydrazine and is often considered an unwanted impurity in UDMH.[8][9]

It is used to induce colon tumours in experimental animals - particularly mice and feline cell samples.[6]

Synthesis

The synthesis of symmetrical dimethylhydrazine is a two-step reaction. First N,N′-bis(ethoxycarbonyl)hydrazide is prepared by elimination of HCl from ethyl chloroformate (2 eq, R1) and hydrazine (1 eq, R1) in the presence of NaOH (2 eq, R1).[10] Then the N,N′-bis(ethoxycarbonyl)hydrazide (1 eq, R2) is reduced by lithium aluminum hydride (6 eq, R2) to form symmetrical dimethylhydrazine.[11]

Reactivity

The reactive groups of symmetrical dimethyl hydrazine are the NH-groups. Both can accept and donate hydrogen bonds, making it soluble in water. The NH-groups can also act as a nucleophile and as a base.[12]

Biotransformation

Symmetrical dimethylhydrazine is first oxidized to azomethane which is then oxidized to azoxymethane. This compound is subsequently hydroxylated to methylazoxymethanol (MAM). These processes occur mostly in the liver, and the hydroxylation step is mediated by cytochrome P450 enzymes.[6][13][14]

MAM is chemically unstable and can spontaneously decompose to formaldehyde, water and nitrogen. In this decomposition, the methyldiazonium ion is formed, which can alkylate DNA and increase the risk of mismatched bases.[6][13][14]

Adverse effects

Chronic exposure of symmetrical dimethylhydrazine led to adverse effects in multiple organs in animals, but its most prominent effect is carcinogenicity. This has been reported in several animal experiments, including rats and mice.[10]

1,2-dimethylhydrazine is classified as a category 2 carcinogen, meaning that there is a significant probability that it can cause cancer in humans as well.[15]

Use and exposure risk

Symmetrical dimethylhydrazine is mainly used experimentally for its carcinogenic properties, particularly to induce colon cancer in laboratory animals for cancer research.[6] Its isomer, unsymmetrical dimethylhydrazine, is widely used in rocket fuel.[7]

Because symmetrical dimethylhydrazine is not used commercially, it is unlikely to be released into the environment in large volumes. When released into the air, hydrazine compounds are relatively quickly decomposed by reactive compounds in the air. Also, in soil or water hydrazines usually do not persist for longer than a few weeks.[16]

Human exposure is therefore unlikely. Laboratory staff that works with the compound would be most at risk. It might also be possible to come into contact through hazardous waste sites, although unlikely.[16]

Molecular mechanism of action

Symmetrical dimethylhydrazine is an indirect-acting genotoxin, meaning its carcinogenicity depends on the metabolization to methyldiazonium ions.[13] Methyldiazonium is a strong methylating agent due to its electrophilic nature and can methylate nucleotide bases in DNA.[14][17]

Methylation occurs most frequently at the N7 or O6 sites of guanine[14][18], but it can also methylate at the C8 site of guanine and at the N3 site of adenine, as well as at the O4 site of thymine.[19]

The methylated base may mispair during DNA replication. For example, methylated guanine can pair with thymine, instead of cytosine.[20] This is followed by subsequent replication, which leads to further mispairing and could mutate a GC pair to an AT pair.[6] When mutations occur in certain genes a neoplasm can be initiated.[21]

Toxicology data

The International Agency of Research on Cancer (IARC) has classified symmetrical dimethyl hydrazine as part of group 2A of the carcinogenesis classification, meaning it is probably carcinogenic to humans.[15] Although the effects of symmetrical dimethyl hydrazine have not been studied on humans in vivo, there is sufficient evidence acquired from animal studies. Similar patterns of DNA damage in humans and a wide range of animals have been observed in vitro, caused by dimethyl hydrazine.[12]

The ILO-WHO International Chemical Safety Cards (ICSCs) warns that symmetrical dimethyl hydrazine can be absorbed into the body by inhalation, ingestion and possibly through the skin contact.[22] Depending on the route of exposure and on the species tested, the LD50 ranged from tens to several hundred mg/kg.[5]

The primary target appears to be the intestines, where morphological and biochemical changes have been observed in the intestinal epithelium after subcutaneous injection.[23]

References

  1. ^ a b c d 74-79-3 1,2-Dimethylhydrazine
  2. ^ 1,2-Dimethylhydrazine from PubChem
  3. ^ Record of 1,2-Dimethylhydrazin in the GESTIS Substance Database of the Institute for Occupational Safety and Health, accessed on 21 March 2008.
  4. ^ "1,2-Dimethylhydrazine". pubchem.ncbi.nlm.nih.gov. Retrieved 22 December 2021.
  5. ^ a b PubChem. "1,2-Dimethylhydrazine". pubchem.ncbi.nlm.nih.gov. Retrieved 2026-03-14.
  6. ^ a b c d e f Venkatachalam, Karthikkumar; Vinayagam, Ramachandran; Arokia Vijaya Anand, Mariadoss; Isa, Nurulfiza Mat; Ponnaiyan, Rajasekar (2020-04-24). "Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review". Toxicology Research. 9 (1): 2–18. doi:10.1093/toxres/tfaa004. ISSN 2045-4538. PMC 7233314. PMID 32440334.
  7. ^ a b Elizaveta, Ivanova,; Margarita, Osipova,; Tatyana, Vasilieva,; Alexey, Eremkin,; Svetlana, Markova,; Ekaterina, Zazhivihina,; Svetlana, Smirnova,; Yurii, Mitrasov,; Oleg, Nasakin, (2023-01). "The Recycling of Substandard Rocket Fuel N,N-Dimethylhydrazine via the Involvement of Its Hydrazones Derived from Glyoxal, Acrolein, Metacrolein, Crotonaldehyde, and Formaldehyde in Organic Synthesis". International Journal of Molecular Sciences. 24 (24). doi:10.3390/ijm. ISSN 1422-0067. Archived from the original on 2025-08-11. {{cite journal}}: Check date values in: |date= (help)CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  8. ^ Schmidt, Eckart W. (2022-12-31), "Dimethylhydrazines Part 1", Encyclopedia of Liquid Fuels, De Gruyter, pp. 1333–1499, doi:10.1515/9783110750287-016/html?srsltid=AfmBOooWH3HZLtBm1gq4_kCW9WVpw538TC4qGRDIt86ZhdUmikiD8mPu, ISBN 978-3-11-075028-7, retrieved 2026-03-14{{citation}}: CS1 maint: work parameter with ISBN (link)
  9. ^ Cruse, J. P.; Lewin, M. R.; Ferulano, G. P.; Clark, C. G. (1978-12). "Co-carcinogenic effects of dietary cholesterol in experimental colon cancer". Nature. 276 (5690): 822–825. doi:10.1038/276822a0. ISSN 1476-4687. {{cite journal}}: Check date values in: |date= (help)
  10. ^ a b Waki, Kunio; Zhao, Jincai; Horikoshi, Satoshi; Watanabe, Natsuko; Hidaka, Hisao (2000-08-01). "Photooxidation mechanism of nitrogen-containing compounds at TiO2/H2O interfaces: an experimental and theoretical examination of hydrazine derivatives". Chemosphere. 41 (3): 337–343. doi:10.1016/S0045-6535(99)00500-7. ISSN 0045-6535.
  11. ^ pubs.acs.org. doi:10.1021/ja01589a040 https://pubs.acs.org/action/cookieAbsent. Retrieved 2026-03-14. {{cite web}}: Missing or empty |title= (help)
  12. ^ a b PubChem. "Hazardous Substances Data Bank (HSDB) : 4039". pubchem.ncbi.nlm.nih.gov. Retrieved 2026-03-14.
  13. ^ a b c Fiala, ES (November 1977). <2436::AID-CNCR2820400908>3.0.CO;2-U "Investigations into the metabolism and mode of action of the colon carcinogens 1,2-dimethylhydrazine and azoxymethane".
  14. ^ a b c d Hartwig, A (2021). "1,2-Dimethylhydrazine".
  15. ^ a b "List of Classifications". Retrieved 2026-03-14.
  16. ^ a b TOXICOLOGICAL PROFILE FOR HYDRAZINES. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. September 1997.{{cite book}}: CS1 maint: date and year (link)
  17. ^ Pozharisski, K. M.; Shaposhnikov, J. D.; Petrov, A. S.; Likhachev, A. J. (1976-01-01). "Distribution and carcinogenic action of 1,2-dimethylhydrazine (SDMH) in rats". Zeitschrift für Krebsforschung und Klinische Onkologie. 87 (1): 67–80. doi:10.1007/BF00285075. ISSN 1432-1335.
  18. ^ Autrup, Herman; Schwartz, Rochelle D.; Essigmann, John M.; Smith, Lee; Harris, Curtis C.; Trump, Benjamin F. (1981). "Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon". Teratogenesis, Carcinogenesis, and Mutagenesis. 1 (1): 3–13. doi:10.1002/tcm.1770010103. ISSN 1520-6866.
  19. ^ Likhachev AL, Petrov AS, P’rvanova LG, Pozharisski KM. Mechanism of methylation of DNA bases by symmetrical dimethylhydrazine.
  20. ^ Lawley PD. Carcinogenesis by alkylating agents. In: Chemical Carcinogens. Washington (DC): American Chemical Society; 1984.
  21. ^ Pegg, A. E. (1990), Cooper, Colin S.; Grover, Philip L. (eds.), "DNA Repair and Carcinogenesis by Alkylating Agents", Chemical Carcinogenesis and Mutagenesis II, Berlin, Heidelberg: Springer, pp. 103–131, doi:10.1007/978-3-642-74778-6_5, ISBN 978-3-642-74778-6, retrieved 2026-03-14{{citation}}: CS1 maint: work parameter with ISBN (link)
  22. ^ "ICSC 1662 - 1,2-DIMETHYLHYDRAZINE". chemicalsafety.ilo.org. Retrieved 2026-03-14.
  23. ^ gestis.dguv.de https://gestis.dguv.de/data?name=034110&lang=en. Retrieved 2026-03-14. {{cite web}}: Missing or empty |title= (help)
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