M-Terphenyl

The earliest known synthesis of meta-terphenyl was completed in 1866 by Pierre Eugène Marcellin Berthelot by heating benzene to high temperatures leading to a mixture of hydrocarbons including a mixture of meta-terphenyl and para-terphenyl. Meta-terphenyl was isolated in 1874 by Gustav Schultz (1851–1928) by taking the mixture of the compounds, mixing them in a solvent and allowing meta-terphenyl to melt off as it has a lower melting and boiling point than para-terphenyl. Meta-terphenyl, and other aromatic compounds, remained of much interest to scientists in throughout the end of the 20th century, with many of the physical properties being measured and compared during this time. This also led to the first alternate form of meta-terphenyl synthesis, which involved passing gaseous benzene and toluene through a hot glass tube.{{Cite journal |last=Carnelley |first=Thos |date=1880-01-01 |title=LXV.—Action of heat on the mixed vapours of benzene and toluene. Two new methylene-diphenylenes |url=https://pubs.rsc.org/en/content/articlelanding/1880/ct/ct8803700701 |journal=Journal of the Chemical Society, Transactions |language=en |volume=37 |pages=701–720 |doi=10.1039/CT8803700701 |issn=0368-1645}}

By the 1930s, focus had shifted to experimenting with the reactivity of meta-terphenyl and its potential use as a ligand. The first verified modified version of meta-terphenyl was created in 1932 by Arthur Wardner and Alexander Lowy and led to the creation of nitro-substituted meta-terphenyls as well as amino-meta-terphenyls from the oxidation of the nitro-substituted compounds.{{Cite journal |last1=Wardner |first1=C. Arthur |last2=Lowy |first2=Alexander |title=Nitration of Meta-Diphenylbenzene and Derivatives of Nitro-Meta-Diphenylbenzene1 |date=1932 |url=https://pubs.acs.org/doi/abs/10.1021/ja01345a051 |journal=Journal of the American Chemical Society |language=en |volume=54 |issue=6 |pages=2510–2515 |doi=10.1021/ja01345a051 |issn=0002-7863|url-access=subscription }} Walter and Kathryn Cook halogenated meta-terphenyl with chlorine and bromine with further applications such as use in as Grignard reaction, the first such suggestion for meta-terphenyl as a ligand for a main group element.{{Cite journal |last1=Cook |first1=Walter A. |last2=Cook |first2=Kathryn Hartkoff |date=1933 |title=The Halogenation of Meta-Diphenylbenzene. I. The Monochloro and Monobromo Derivatives |url=https://pubs.acs.org/doi/abs/10.1021/ja01330a059 |journal=Journal of the American Chemical Society |language=en |volume=55 |issue=3 |pages=1212–1217 |doi=10.1021/ja01330a059 |issn=0002-7863|url-access=subscription }} They later confirmed their results using the Stepanow Method.{{Cite journal |last1=Cook |first1=Walter A. |last2=Cook |first2=Kathryn Hartkoff |date=1933-05-01 |title=Determination of Nuclear Halogens in Organic Compounds |url=https://pubs.acs.org/doi/abs/10.1021/ac50083a016 |journal=Industrial & Engineering Chemistry Analytical Edition |language=en |volume=5 |issue=3 |pages=186–188 |doi=10.1021/ac50083a016 |issn=0096-4484|url-access=subscription }} This trend continued with C.K. Breadsher and I. Swerlick publishing a review of all known reactions that meta-terphenyl could undergo.{{Cite journal |last1=Bradsher |first1=C. K. |last2=Swerlick |first2=I. |date=1950 |title=Reactions in the m-Terphenyl Series¹ |url=http://dx.doi.org/10.1021/ja01165a100 |journal=Journal of the American Chemical Society |volume=72 |issue=9 |pages=4189–4192 |doi=10.1021/ja01165a100 |issn=0002-7863|url-access=subscription }} G. R. Ames also wrote an article detailing not only reactions of meta-terphenyls, but also covering all the different experimental methods to obtain meta-terphenyl known at the time.{{Cite journal |last=Ames |first=G. R. |date=1958 |title=The Synthesis of Substituted Terphenyls |url=https://pubs.acs.org/doi/abs/10.1021/cr50023a004 |journal=Chemical Reviews |language=en |volume=58 |issue=5 |pages=895–923 |doi=10.1021/cr50023a004 |issn=0009-2665|url-access=subscription }}

During this time, the method of producing meta-terphenyl had remained the same. While people did experiment with other ways to obtain the compound, for the most part the method of heating benzene in a glass tube remained the primary method. In 1948, however, G. Woods and Irwin Tucker put forth an alternative method. Instead of heating benzene, they found that a combination of dihydroresocinol and two equivalents of phenyllithium would create unsymmetrical meta-terphenyl molecules.{{Cite journal |last1=Woods |first1=G. Forrest |last2=Tucker |first2=Irwin W. |date=1948 |title=Synthesis of m-Diarylbenzenes |url=https://pubs.acs.org/doi/abs/10.1021/ja01190a035 |journal=Journal of the American Chemical Society |language=en |volume=70 |issue=10 |pages=3340–3342 |doi=10.1021/ja01190a035 |pmid=18891854 |issn=0002-7863|url-access=subscription }} This was significant as the previous method required the separation of meta-terphenyl from other compounds and this novel synthesis allowed meta-terphenyls to be the major product and much more easily isolatable. This method would remain the most popular form of making meta-terphenyls until the end of the 20th century.

File:Woods-Tucker Method.svg

It was during this time that it was discovered that meta-terphenyls occurred in nature. In 1975, Karl-Werner Glombitza, Hans-Willi Rauwald, and Gert Eckhardt isolated two meta-terphenyls from the algae Fugus vesiculosus.{{Cite journal |last1=Glombitza |first1=Karl-Werner |last2=Rauwald |first2=Hans-Willi |last3=Eckhardt |first3=Gert |date=1975-06-01 |title=Fucole, polyhydroxyoligophenyle aus Fucus vesiculosus |url=https://www.sciencedirect.com/science/article/pii/S0031942200986370 |journal=Phytochemistry |language=de |volume=14 |issue=5 |pages=1403–1405 |doi=10.1016/S0031-9422(00)98637-0 |bibcode=1975PChem..14.1403G |issn=0031-9422|url-access=subscription }} More naturally occurring meta-terphenyls have been isolated since then and have shown promising applications in the field of biochemistry.

As the demand for meta-terphenyl and its derivatives grew through the latter half of the 20th century, it became necessary to increase the yield of reactions producing meta-terphenyls as well as have the ability to uniquely create symmetric and unsymmetric meta-terphenyls to investigate their reactivity as well utilize their increased steric control. Such a method was discovered by Akbar Saednya and Harold Hart in 1986. Using an excess of Grignard reagent that had a phenyl group attached, meta-terphenyl was able to be made quickly, in one step, with a relatively high yield. This method also allowed for a variety of meta-terphenyl compounds to be made as so long as it could successfully be made into a Grignard reagent.

File:Saedyna-Hart Method.svg

This method continues to remain very popular in terms of the creation of symmetrical meta-terphenyl compounds, but that has not stopped attempts to quicken synthesis, increase yield, and create more sterically bulky m-terphenyls. The method developed by Saednya and Hart has provided the basis for improved synthesis of meta-terphenyls and has often been used as a comparison when it comes to resulting structures and methods.{{Cite journal |last1=Olaru |first1=Marian |last2=Beckmann |first2=Jens |last3=Raţ |first3=Ciprian I. |date=2014-06-23 |title=Polyfluorinated Functionalized m -Terphenyls. New Substituents and Ligands in Organometallic Synthesis |url=https://pubs.acs.org/doi/10.1021/om500244y |journal=Organometallics |language=en |volume=33 |issue=12 |pages=3012–3020 |doi=10.1021/om500244y |issn=0276-7333|url-access=subscription }} Saednya and Hart continued their work and provided two alternate paths to create meta-terphenyls in 1996.{{Cite journal |last1=SAEDNYA |first1=A. |last2=HART |first2=H. |date=2010-08-03 |title=ChemInform Abstract: Two Efficient Routes to m-Terphenyls from 1,3-Dichlorobenzenes. |url=http://dx.doi.org/10.1002/chin.199722096 |journal=ChemInform |volume=28 |issue=22 |pages=no |doi=10.1002/chin.199722096 |issn=0931-7597|url-access=subscription }} One involved using a halogenated benzene and three equivalents of the phenyl group attached to the benzene. The second involved a dichloro-substituted benzene and butyl lithium followed by two equivalents of the Grignard reagents mentioned above. This led to increased yields of larger terphenyl compounds, however as the size of the substituents has been hypothesized to have a limit due to the increased steric hindrance of the molecule.

File:SH Second Method.svg

Novel synthesis methods have continued to be developed to this day. One such method involves using an ultrasound bath to make m-terphenyl compounds. By reacting anionic diphenyl molecules with functional ketones in a solution of potassium hydroxide and DMF in an ultrasound bath, a bulky meta-terphenyl molecule can be obtained. While this method does not have the highest yield, it is much quicker being able to be completed within an hour.{{Cite journal |last1=Shetgaonkar |first1=Samata E. |last2=Singh |first2=Fateh V. |date=2019-04-18 |title=Ultrasound-assisted one pot synthesis of polysubstituted meta-terphenyls using ring transformation strategy |url=https://doi.org/10.1080/00397911.2019.1591454 |journal=Synthetic Communications |volume=49 |issue=8 |pages=1092–1102 |doi=10.1080/00397911.2019.1591454 |s2cid=109167395 |issn=0039-7911|url-access=subscription }} Additionally, meta-terphenyl synthesis has begun to become more focused. As opposed to general routes to produce common meta-terphenyl compounds, the shift has been to improve certain derivatives to accomplish particular goals. Examples of this include a method to produce a very sterically hindered meta-terphenyl with the purpose of forming phosphorus-phosphorus double bonds and a heavily fluorinated meta-terphenyl being produced to help stabilize silylium compounds. Additionally, reaction to add other bulky substituents to the center phenyl group has been shown to discourage rotation of the outer phenyl groups in hopes of stabilizing boron and silicon radicals and bonded complexes.{{Cite journal |last1=Smith |first1=Rhett |last2=Ren |first2=Tong |last3=Protasiewicz |first3=John |last4=John |first4=A. |date=2002 |title=A Robust, Reactive, and Remarkably Simple to Prepare Sterically Encumbered meta-Terphenyl Ligand |journal=European Journal of Inorganic Chemistry |volume=2002 |issue=11 |pages=2779–2783|doi=10.1002/1099-0682(200211)2002:11<2779::AID-EJIC2779>3.0.CO;2-Q }}{{Cite journal |last1=Stanciu |first1=Corneliu |last2=Richards |first2=Anne F. |last3=Fettinger |first3=James C. |last4=Brynda |first4=Marcin |last5=Power |first5=Philip P. |date=2006-05-15 |title=Synthesis and characterization of new, modified terphenyl ligands: Increasing the rotational barrier for flanking rings |url=https://www.sciencedirect.com/science/article/pii/S0022328X06001057 |journal=Journal of Organometallic Chemistry |language=en |volume=691 |issue=11 |pages=2540–2545 |doi=10.1016/j.jorganchem.2006.01.046 |issn=0022-328X|url-access=subscription }}

Meta-terphenyls have a variety of uses in fields of chemistry. Their large size can help to sterically force a certain reaction to take place, however they are mainly used to stabilize compounds that would be unstable otherwise. One such area of study is in main group chemistry. An example of this can be seen in the formation of heavier carbene analogues, where bulky meta-terphenyl ligands were able to provide enough steric protection to stabilize newly created bismuthenium and stibenium ions, the first reported carbene analogs that were not in Group 14.{{Cite journal |last1=Olaru |first1=Marian |last2=Duvinage |first2=Daniel |last3=Lork |first3=Enno |last4=Mebs |first4=Stefan |date=2018 |title=Heavy Carbene Analogues: Donor-Free Bismuthenium and Stibenium Ions |journal=Angewandte Chemie |volume=57 |issue=32 |pages=10080–10084|doi=10.1002/anie.201803160 |pmid=29644767 }} Additionally, meta-terphenyl ligands were used to stabilize phosphorus-phosphorus double bonds.{{Cite journal |last1=Protasiewicz |first1=John D. |last2=Washington |first2=Marlena P. |last3=Gudimetla |first3=Vittal B. |last4=Payton |first4=John L. |last5=Cather Simpson |first5=M. |date=2010-12-15 |title=A closer look at the phosphorus–phosphorus double bond lengths in meta-terphenyl substituted diphosphenes |url=https://www.sciencedirect.com/science/article/pii/S0020169310004779 |journal=Inorganica Chimica Acta |series=Special Volume: Dedication to Professor Rheingold |language=en |volume=364 |issue=1 |pages=39–45 |doi=10.1016/j.ica.2010.07.018 |issn=0020-1693|url-access=subscription }} This was proven multiple times with a variety of different meta-terphenyl compounds being used to confirm the result and led to the confirmation of the appropriate length of a phosphorus-phosphorus double bond.

File:Bismuthium ion.svg

Another relevant field of study where meta-terphenyls have shown significant use is organometallics. One such application has been in the creation of paramagnetic organometallic compounds. Due to the steric hindrance provided by m-terphenyls, the creation of certain main group-metal aryl complexes has been made possible, which provide the opportunity to create species with a broad range of reactivity, including with small molecules such as ammonia, carbon dioxide, and oxygen. It has additionally helped in methyl-bridging bonds between transition metal centers.{{Cite journal |last1=Ni |first1=Chengbao |last2=Power |first2=Philip P. |date=2009-11-23 |title=Methyl-Bridged Transition Metal Complexes (M = Cr−Fe) Supported by Bulky Terphenyl Ligands |url=https://pubs.acs.org/doi/10.1021/om900724p |journal=Organometallics |language=en |volume=28 |issue=22 |pages=6541–6545 |doi=10.1021/om900724p |issn=0276-7333|url-access=subscription }}

M-terphenyls have also been quite helpful in getting preliminary structures of divalent lithium and sodium, although both molecules had substantial stabilization from the electron-rich meta-terphenyl group.{{Cite journal |last1=Clyburne |first1=Jason A. C |last2=McMullen |first2=Nichole |date=2000-12-01 |title=Unusual structures of main group organometallic compounds containing m-terphenyl ligands |url=https://www.sciencedirect.com/science/article/pii/S0010854500003179 |journal=Coordination Chemistry Reviews |language=en |volume=210 |issue=1 |pages=73–99 |doi=10.1016/S0010-8545(00)00317-9 |issn=0010-8545|url-access=subscription }} M-terphenyls have also helped, along with the electronic support of sodium ions, to stabilize the first gallium-gallium triple bond, although this is contested due to the high coordination of the sodium atoms in the complex. A similar approach meshing the methods to form a phosphorus-phosphorus double bonds and a gallium-gallium triple bond allowed researched to create and isolate the first germanium-germanium double bond. Meta-terphenyl continues to play an important part of organometallic chemistry, as well as main group chemistry, due to its kinetic stabilization of molecules and its thermodynamic influence on the energies between molecules.

File:Iron-Bridged Complex.svg

Meta-terphenyl ligands can be used on their own in the field of biochemistry. Due to its composition and shape, meta-terphenyl can be used as the basis for the formation of synthetic proteins that can bind to carbohydrates, lectins. This is due to the large twisted shape of meta-terphenyl, when not hindered by bulkier substituents used in organometallics and main-group chemistry, which may opt to increase the rotational barrier of the molecule. In this way, synthetic receptors for sugars such as disaccharides can be bound temporarily before being used in further experiments. This process, while it continues to be developed, has many promising applications such as the prevention and treatment of bacterial infections.{{Cite journal |last=Mazik |first=Monika |date=2008-05-05 |title=Design of Lectin Mimetics |url=http://dx.doi.org/10.1002/cbic.200800038 |journal=ChemBioChem |volume=9 |issue=7 |pages=1015–1017 |doi=10.1002/cbic.200800038 |pmid=18366054 |s2cid=11426160 |issn=1439-4227|url-access=subscription }}

Another field that often uses meta- terphenyls is transition metal chemistry. They are most relevant in attaining low-coordinate metal centers. This is because their size makes it difficult for a lot of ligands to bond to a metal center.{{Cite journal |last1=Sharpe |first1=Helen R. |last2=Geer |first2=Ana M. |last3=Williams |first3=Huw E. L. |last4=Blundell |first4=Toby J. |last5=Lewis |first5=William |last6=Blake |first6=Alexander J. |last7=Kays |first7=Deborah L. |date=2017-01-10 |title=Cyclotrimerisation of isocyanates catalysed by low-coordinate Mn(II) and Fe(II) m-terphenyl complexes |url=https://pubs.rsc.org/en/content/articlelanding/2017/cc/c6cc07243g |journal=Chemical Communications |language=en |volume=53 |issue=5 |pages=937–940 |doi=10.1039/C6CC07243G |pmid=28008435 |issn=1364-548X|hdl=10261/345646 |hdl-access=free }} This has shown to be quite useful in the area of reaction chemistry and they have shown to be quite helpful a number of catalysis reactions, such as those involving isocyanates. This has allowed for certain reactions to occur in a shorter amount of time and with generally mild conditions.

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Category:Aromatic hydrocarbons

Category:Phenyl compounds