View source for 1,4-Butanediol

{{short description|One of four stable isomers of butanediol}}
{{Use dmy dates|date=November 2022}}
{{CS1 config|mode=cs2}}

{{chembox
|Watchedfields = changed
|verifiedrevid = 477205926
|Name = 1,4-Butanediol
|ImageFile1 = 1,4-butanediol.svg
|ImageClass1 = skin-invert-image
|ImageFile2 = 1,4-Butanediol-3D-balls.png
|ImageName = 1,4-Butanediol
|PIN = Butane-1,4-diol
|OtherNames = Tetramethylene glycol
|Section1 = {{Chembox Identifiers
|InChI = 1/C4H10O2/c5-3-1-2-4-6/h5-6H,1-4H2
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C4H10O2/c5-3-1-2-4-6/h5-6H,1-4H2
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = WERYXYBDKMZEQL-UHFFFAOYSA-N
|SMILES1 = C(CCO)CO
|CASNo = 110-63-4
|CASNo_Ref = {{cascite|correct|CAS}}
|EC_number = 203-786-5
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|DrugBank_Ref = {{drugbankcite|correct|drugbank}}
|DrugBank = DB01955
|ChemSpiderID = 13835209
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 171623
|ChEBI = 41189
|ChEBI_Ref = {{ebicite|correct|EBI}}
|RTECS = EK0525000
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 7XOO2LE6G3
|PubChem = 8064
|SMILES = OCCCCO
}}
|Section2 = {{Chembox Properties
|Properties_ref = <ref>{{RubberBible62nd|page=C-190|mode=cs2}}</ref><ref name="ICSC">{{ICSC-ref|11|04|name=1,4-Butanediol|date=March 1999}}</ref>
|C=4 | H=10 | O=2
|Density = 1.0171 g/cm<sup>3</sup> (20 °C)
|MeltingPtC = 20.1
|BoilingPtC = 235
|Solubility = Miscible
|SolubleOther = Soluble
|Solvent = ethanol
|RefractIndex = 1.4460 (20 °C)
|MagSus = −61.5·10<sup>−6</sup> cm<sup>3</sup>/mol
}}
|Section3 = {{Chembox Hazards
|Hazards_ref = <ref>{{citation |title=HSNO Chemical Classification Information Database |url=https://www.epa.govt.nz/database-search/chemical-classification-and-information-database-ccid/view/1FE05653-F46B-45F6-AE62-B5D125DD68A0|publisher=New Zealand Environmental Protection Authority }}</ref><ref>{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/8064#datasheet=LCSS&section=GHS-Classification|title=1,4-Butanediol Laboratory Chemical Safety Summary|mode=cs2}}</ref>
|GHSPictograms = {{GHS exclamation mark|Acute Tox. (oral) 4}}
|GHSSignalWord = WARNING
|HPhrases = {{H-phrases|302|336}}
|PPhrases = {{P-phrases|261|264|270|271|301+312|304+340|312|330|403+233|405|501}}
|NFPA-H = 1
|NFPA-F = 1
|NFPA-R = 0
|NFPA-S =
|FlashPtC = 121
|FlashPt = (open&nbsp;cup)
|AutoignitionPtC = 350
}}
|Section4 = {{Chembox Related
|OtherFunction = [[1,2-Butanediol]]<br />[[1,3-Butanediol]]<br />[[2,3-Butanediol]]<br/>[[cis-Butene-1,4-diol]]
|OtherFunction_label = [[butanediol]]s
|OtherCompounds = [[Succinaldehyde]]<br />[[Succinic acid]]
}}
}}

'''1,4-Butanediol''', also called '''Butane-1,4-diol''' (other names include '''1,4-B''', '''BD''', '''BDO''', and '''1,4-BD'''),<ref>{{cite web|url=https://www.webmd.com/vitamins/ai/ingredientmono-21/1-4-butanediol|title=1,4-Butanediol - Uses, Side Effects, and More|website=[[WebMD]]|access-date=31 March 2024}}</ref> is a [[primary alcohol]] and an [[organic compound]] with the [[chemical formula|formula]] HOCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>OH. It is a colorless [[viscosity|viscous]] [[liquid]] first synthesized in 1890 via acidic hydrolysis of N,N'-dinitro-1,4-butanediamine by Dutch chemist Pieter Johannes Dekkers, who called it "tetramethylene glycol".<ref>{{Cite journal |last=Dekkers |first=M. P. J. |date=January 1890 |title=Le glycol tétraméthylénique |url=https://books.google.com/books?id=0RjzAAAAMAAJ&pg=PA92 |journal=[[Recueil des Travaux Chimiques des Pays-Bas]] |language=en |volume=9 |issue=4 |pages=92–102 |doi=10.1002/recl.18900090403 |issn=0165-0513|url-access=subscription }}</ref><ref>{{Cite book |last=Dekkers |first=Pieter Johannes |url=https://books.google.com/books?id=X_8TAQAAIAAJ |title=Over het Tetramethyleenglycol: Proefschr. ... te verdedigen ... door Pieter Johannes Dekkers |date=1890 |publisher=L. van Nifterik Hz. |language=nl}}</ref>

==Synthesis==
[[File:ButaneToDiol.svg|class=skin-invert-image|thumb|left|380px|Conversion of butane to butanediol or butyrolactone via oxidation to maleic anhydride followed by hydrogenation over [[copper chromite]].<ref name=Rylander>{{cite book |doi=10.1002/14356007.a13_487 |chapter=Hydrogenation and Dehydrogenation |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2000 |last1=Rylander |first1=Paul N. |isbn=3-527-30673-0 }}</ref> ]]

In one industrial [[chemical synthesis]], [[acetylene]] reacts with two equivalents of [[formaldehyde]] to form [[butyne-1,4-diol]]. [[Hydrogenation]] of butyne-1,4-diol gives butane-1,4-diol.<ref>{{Cite web |date=2023-07-30 |title=1,4-Butanediol Production And Uses |url=https://chemcess.com/14-butanediol-production-and-uses/ |access-date=2023-07-30 |language=en-US}}</ref> It is also made on an industrial scale from [[maleic anhydride]] in the Davy process, which is first converted to the methyl maleate ester, then hydrogenated. Other routes are from [[butadiene]], [[allyl acetate]] and [[succinic acid]].

A biological route to BD has been commercialized that uses a [[genetically modified organism]].<ref>{{cite web|url=http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/netahtml/PTO/srchnum.htm&r=1&f=G&l=50&s1=8067214.PN.&OS=PN/8067214&RS=PN/8067214|title=United States Patent: 8067214 - Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors|website=uspto.gov|access-date=1 April 2018|mode=cs2}}</ref> The [[biosynthesis]] proceeds via [[4-Hydroxybutyric acid|4-hydroxybutyrate]].

==Industrial use==
Butane-1,4-diol is used industrially as a [[solvent]]{{Additional citation needed|date=October 2024}} and in the manufacture of some types of [[plastic]]s, elastic [[fiber]]s and [[polyurethane]]s. In [[organic chemistry]], 1,4-butanediol is used for the synthesis of [[gamma-butyrolactone|γ-butyrolactone]] (GBL). In the presence of [[phosphoric acid]] and high temperature, it dehydrates to the important solvent [[tetrahydrofuran]].<ref name="kirk1">{{Kirk-Othmer | last1 = Karas | first1 = L. | last2 = Piel | first2 = W. J. | title = Ethers}}</ref> At about 200&nbsp;°C in the presence of soluble [[ruthenium]] [[catalyst]]s, the diol undergoes [[dehydrogenation]] to form [[γ-Butyrolactone|butyrolactone]].<ref>{{Citation | last1 = Zhao | first1 = Jing | last2 = Hartwig | first2 = John F. | author-link2 = John F. Hartwig | year = 2005 | title = Acceptorless, neat, ruthenium-catalyzed dehydrogenative cyclization of diols to lactones | journal = Organometallics | volume = 24 | pages = 2441–46 | doi = 10.1021/om048983m | issue = 10}}</ref> It is used to synthesize [[1,4-Butanediol diglycidyl ether|1,4-butanediol diglycidyl ether]] which is then used as a [[reactive diluent]] for [[epoxy]] resins.<ref>{{Citation |last=Monte |first=Salvatore J. |title=Diluents and viscosity modifiers for epoxy resins |date=1998 |url=https://doi.org/10.1007/978-94-011-5862-6_24 |work=Plastics Additives: An A-Z reference |series=Polymer Science and Technology Series |volume=1 |pages=211–216 |editor-last=Pritchard |editor-first=Geoffrey |place=Dordrecht |publisher=Springer Netherlands |language=en |doi=10.1007/978-94-011-5862-6_24 |isbn=978-94-011-5862-6 |access-date=2022-03-29|url-access=subscription }}</ref>

1,4-Butanediol is used in the production of [[polybutylene terephthalate]] (PBT) plastic.<ref>{{Cite web |title=Polybutylene Terephthalate (PBT) Material Guide & Properties Info |url=https://omnexus.specialchem.com/selection-guide/polybutylene-terephthalate-pbt-plastic |access-date=2023-11-24 |website=omnexus.specialchem.com |language=en|archive-url=https://web.archive.org/web/20231124155646/https://omnexus.specialchem.com/selection-guide/polybutylene-terephthalate-pbt-plastic|archive-date=2023-11-24}}</ref>

World production of butane-1,4-diol was claimed to be about one million metric tons per year and market price is about {{US$|link=yes}}2,000 (€1,600) per ton in 2005. In 2013, worldwide production was claimed to be billions of pounds (consistent with approximately one million metric tons).<ref name="ChemEngmag">{{citation|title=Commercial-scale production of bio-based BDO announced |url=http://www.chemengonline.com/commercial-scale-production-of-bio-based-bdo-announced/ |date=Feb 2013 |newspaper=Chemical Engineering |access-date=2013-02-21 |archive-url=https://web.archive.org/web/20150204185115/http://www.chemengonline.com/commercial-scale-production-of-bio-based-bdo-announced/ |archive-date=2015-02-04 |url-status=live }}</ref>

Almost half of it is dehydrated to [[tetrahydrofuran]] to make fibers such as [[Spandex]].<ref>{{citation | url = http://www.accessmylibrary.com/coms2/summary_0286-15012128_ITM | title = Butanediol (price and demand in market) | date = 12 April 2006 | newspaper = [[Chemical Week]] | access-date = 2008-11-21}}</ref> The largest producer is [[BASF]].<ref>{{citation | title = Malaysia: New 1,4-butanediol plant used below capacity | url = http://findarticles.com/p/articles/mi_qa5358/is_200404/ai_n21348316 | date = April 2004 | newspaper = Asian Textile Business | access-date = 2008-11-21}}</ref>

==Use as a recreational drug==
[[File:Dangerous dietary supplements.gif|thumb|right|FDA warning against products containing GHB and its prodrugs, such as butane-1,4-diol.|352x352px]]
Butane-1,4-diol is also used as a [[recreational drug]] known by some users as "Bute",<ref name="c082">{{cite web | last=Australian Associated Press | title=Date-rape drug 'bute' increasingly linked to sexual assaults in Australia, police say | website=the Guardian | date=2024-05-30 | url=https://www.theguardian.com/society/article/2024/may/30/australia-date-rape-drug-bute-butanediol-sexual-assaults-police-seizure | access-date=2024-05-30}}</ref> "One Comma Four", "Liquid Fantasy", "One Four Bee" or "One Four B-D-O".

Some [[Federal courts of the United States|federal courts]] in the USA have stated that 1,4-butanediol exerts effects similar to its metabolite, [[GABA analogue]] [[Γ-Hydroxybutyric acid|gamma-hydroxybutyrate]] (GHB), but several other federal courts have ruled that it does not.

1,4-but'''e'''nediol (CAS 110-64-5) may be incorrectly sold as 1,4-butanediol but should not be confused with it.

===Pharmacokinetics===
Butane-1,4-diol is rapidly converted into GHB acid by the enzymes [[alcohol dehydrogenase]] and [[aldehyde dehydrogenase]], and differing levels of these enzymes may account for differences in effects and [[side effects]] between users.<ref name="Benzer">{{citation | last1 = Benzer | first1 = Theodore I. | last2 = Cameron | first2 = Scott | last3 = Russi | first3 = Christopher Scott | date = 8 January 2007 | title = Toxicity, Gamma-Hydroxybutyrate | url = http://www.emedicine.com/emerg/topic848.htm | publisher = [[eMedicine]] | access-date = 2009-08-29}}</ref> While co-administration of [[Alcohol (drug)|ethanol]] and GHB already poses serious risks, co-administration of ethanol with 1,4-butanediol will interact considerably and has many other potential risks. This is because the same enzymes that are responsible for metabolizing alcohol also metabolize 1,4-butanediol so there is a strong chance of a dangerous [[drug interaction]].<ref name="Benzer"/><ref name="Poldrugo">{{citation | last1 = Poldrugo | first1 = Flavio | last2 = Snead III | first2= O. Carter | year = 1984 | title = 1,4-butanediol, γ-hydroxybutyric acid and ethanol: Relationships and interactions | journal = Neuropharmacology | volume = 23 | issue = 1 | pages = 109–13 | doi = 10.1016/0028-3908(84)90226-0 | pmid = 6717752| s2cid = 54415695}}</ref> Emergency room patients who overdose on both ethanol and 1,4-butanediol often present with symptoms of [[alcohol intoxication]] initially and as the ethanol is metabolized the 1,4-butanediol is then able to better compete for the enzyme and a second period of intoxication ensues as the 1,4-butanediol is converted into GHB.<ref name="Benzer"/>
[[File:GHB metabolic pathway.svg|class=skin-invert-image|thumb|center|600px|Metabolic pathway of butane-1,4-diol, [[gamma-butyrolactone|γ-butyrolactone]] and γ-hydroxybutyric acid (GHB).]]

===Pharmacodynamics===
Butane-1,4-diol seems to have two types of pharmacological actions. The major psychoactive effects of 1,4-butanediol are because it is metabolized into GHB; however there is a study suggesting that 1,4-butanediol may have potential alcohol-like pharmacological effects on its own.<ref name="Poldrugo"/> The study arrived at this conclusion based on the finding that butane-1,4-diol coadministered with ethanol led to potentiation of some of the behavioral effects of ethanol. However, potentiation of ethanol's effects may simply be caused by competition for the [[alcohol dehydrogenase]] and [[aldehyde dehydrogenase]] enzymes with co-administered 1,4-butanediol. The shared metabolic rate-limiting steps thus leads to slowed metabolism and clearance for both compounds including ethanol's known toxic metabolite [[acetaldehyde]].

Another study found no effect following intracerebroventricular injection of butane-1,4-diol in rats.<ref>{{Citation | pmid = 17100847 | year = 2006 | last1 = Carter | first1 = LP | last2 = Koek | first2 = W | last3 = France | first3 = CP | title = Lack of effects of GHB precursors GBL and 1,4-BD following i.c.v. Administration in rats | volume = 24 | issue = 9 | pages = 2595–600 | doi = 10.1111/j.1460-9568.2006.05146.x | journal = The European Journal of Neuroscience| s2cid = 24609982}}</ref> This contradicts the hypothesis of butane-1,4-diol having inherent alcohol-like pharmacological effects.

Like gamma-hydroxybutyric acid, butane-1,4-diol is safe only in small amounts. Adverse effects in higher doses include nausea, vomiting, dizziness, sedation, vertigo, and potentially death if ingested in large amounts. Anxiolytic effects are diminished and side effects increased when used in combination with alcohol.

===Legality===
While butane-1,4-diol is not currently [[U.S. Schedules of Controlled Substances|scheduled federally in the United States]],<ref>{{Cite web|url=https://www.law.cornell.edu/uscode/text/21/841|title=21 U.S. Code § 841 - Prohibited acts A|website=LII / Legal Information Institute|access-date=2016-08-02|mode=cs2}}</ref> a number of states have classified 1,4-butanediol as a controlled substance. Individuals have been prosecuted for possession of 1,4-butanediol under the [[Federal Analog Act]] as substantially similar to GHB.<ref>USA v Washam (2002) 312 F.3d 926, 930; http://cases.justia.com/us-court-of-appeals/F3/312/926/608696/</ref> A federal case in New York in 2002 ruled that 1,4-butanediol could not be considered an [[structural analog|analog]] of GHB under federal law,<ref>{{cite web|url=http://www.erowid.org/chemicals/14b/14b_law1.shtml|title=Erowid 1,4-Butanediol Vault : Law : New York Federal Court Rules Analogue Act Unconstitutionally Vague with regard to 1,4-Butanediol|website=www.erowid.org|access-date=1 April 2018|mode=cs2}}</ref> but that decision was later overturned by the Second Circuit.<ref>United States v. Roberts, 363 F.3d 118 (2d Cir. 2004); https://scholar.google.com/scholar_case?case=13457043198797192346&q=363+F.3d+118&hl=en&as_sdt=6,39</ref> A jury in Federal District Court in Chicago found that 1,4-butanediol was not an analog of GHB under federal law, which was not disputed on the case's appeal to the Seventh Circuit Court of Appeals, however this finding did not affect the outcome of the case.<ref>United States v. Turcotte, 405 F.3d 515 (7th Cir. 2005) "With specific regard to 1,4 Butanediol, the jury has returned a special verdict which states that 1,4-Butanediol is not a Schedule I Narcotic Drug Controlled Substance analogue, because 1,4-Butanediol's chemical structure is not significantly similar to the chemical structure of GHB.</ref>  In the [[United Kingdom]], 1,4-butanediol was scheduled in December 2009 (along with another GHB precursor, [[gamma-butyrolactone]]) as a [[Misuse of Drugs Act 1971|Class C]] controlled substance. In Germany, the drug is not explicitly illegal, but might also be treated as illegal if used as a drug. It is controlled as a Schedule VI [[Precursor (chemistry)|precursor]] in [[Canada]].

===2007 contamination of Bindeez toy===
{{see also|Bindeez}}
A toy called "[[Bindeez]]" ("Aqua Dots" in North America) was recalled by the distributor in November 2007 because of the presence of butane-1,4-diol. The toy consists of small beads that stick to each other by sprinkling water. Butane-1,4-diol was detected by [[GC-MS]].<ref>{{citation | last = Wang | first = Linda | date = 9 November 2007 | title = Industrial Chemical Sullies Popular Children's Toy | url = http://pubs.acs.org/cen/news/85/i46/8546news11.html | newspaper = [[Chemical & Engineering News]] | access-date=2009-08-11}}</ref> The production plant seems to have intended to cut costs by replacing less toxic [[pentane-1,5-diol]] with butane-1,4-diol. ChemNet China listed the price of butane-1,4-diol at between about US$1,350–2,800 per metric ton, while the price for 1,5-pentanediol is about US$9,700 per metric ton.<ref>{{citation | title = US mother says her son began to stumble and vomit after eating Chinese-made toy, now recalled | url = http://news.bostonherald.com/news/national/general/view.bg?articleid=1043462&srvc=next_article | publisher = Associated Press | date = 8 November 2007 | newspaper = [[Boston Herald]]}}</ref>

===2021 poisoning at Darmstadt Technical University===
In August 2021, several people fell severely ill after consuming drinks at building L2.01 at the Lichtwiese Campus of [[Darmstadt Technical University]], Germany. Seven showed severe symptoms, two were transported to a hospital in [[Frankfurt am Main]], and a 30-year-old person was, for a time, in a critical state. Butane-1,4-diol had been detected in milk packages, as well as in water filters. At the location, detectives also found [[Monobromophenol|bromophenols]] and [[dicyclohexylamine]].<ref>{{Cite web|url=https://www.stern.de/panorama/stern-crime/vergiftungen-an-tu-darmstadt--ermittler-finden-k--o--tropfen-in-kueche-30687682.html|title=Ermittler finden nach Vergiftungen an TU Darmstadt offenbar K.-o.-Tropfen in Küche|date=2021-08-27|access-date=2021-09-01|website=[[Stern (magazine)|Stern]]|mode=cs2}}</ref>

==Derivatives==
A variety of 1,4-butanediol [[chemical derivative|derivative]]s are GHB-like drugs or [[GHB receptor]] [[agonist]]s. These include [[GHB]] itself, [[γ-butyrolactone]] (GBL), [[aceburic acid]], [[ethyl acetoxy butanoate]] (EAB), [[Γ-crotonolactone]], [[γ-hydroxybutyraldehyde]], [[γ-hydroxyvaleric acid]] (GHV), [[γ-valerolactone]], [[γ-hydroxycrotonic acid]] (GHC or T-HCA), and [[4-hydroxy-4-methylpentanoic acid]] (UMB68), among others. An [[structural analog|analogue]] that is not a 1,4-butanediol derivative but is related and still shows [[affinity (pharmacology)|affinity]] for the GHB receptor is [[3-chloropropanoic acid]] (UMB66).

==See also==
* [[1,3-Butanediol]]
* [[1,4-Butanediol diglycidyl ether]]
* [[2-Methyl-2-propyl-1,3-propanediol]]
* [[4-Amino-1-butanol]]

==References==
{{reflist|30em}}

== External links ==
* {{ICSC|1104|11}}
* {{SIDS|name=1,4-Butanediol|id=110634|date=November 2002}}
* [https://www.whatsinproducts.com/chemicals/view/1/1443/000110-63-4/1,4-Butanediol Record] in the Household Products Database of [[United States National Library of Medicine|NLM]]

{{Hypnotics}}
{{GHB receptor modulators}}
{{GABA receptor modulators}}
{{Chemical classes of psychoactive drugs}}

{{DEFAULTSORT:Butanediol, 1, 4-}}

[[Category:Alcohol solvents]]
[[Category:Prodrugs]]
[[Category:Sedatives]]
[[Category:Alkanediols]]
[[Category:Neurotransmitter precursors]]
[[Category:GABAB receptor agonists]]
[[Category:GHB receptor agonists]]
[[Category:Designer drugs]]
[[Category:GABA analogues]]
[[Category:Primary alcohols]]
[[Category:1,4-Butanediyl compounds]]