Adamantane

Template:Short description Template:Cs1 config Template:Distinguish Template:Chembox Adamantane is an organic compound with formula C₁₀H₁₆ or, more descriptively, (CH)₄(CH₂)₆. Adamantane molecules can be described as the fusion of three cyclohexane rings. The molecule is both rigid and virtually stress-free. Adamantane is the most stable isomer of C₁₀H₁₆. The spatial arrangement of carbon atoms in the adamantane molecule is the same as in the diamond crystal. This similarity led to the name adamantane, which is derived from the Greek adamantinos (relating to steel or diamond).<ref>Alexander Senning. Elsevier's Dictionary of Chemoetymology. Elsevier, 2006, p. 6 Template:ISBN.</ref> It is a white solid with a camphor-like odor. It is the simplest diamondoid.

The discovery of adamantane in petroleum in 1933 launched a new field of chemistry dedicated to the synthesis and properties of polyhedral organic compounds. Adamantane derivatives have found practical application as drugs, polymeric materials, and thermally stable lubricants.

History and synthesis

In 1924, H. Decker suggested the existence of adamantane, which he called decaterpene.<ref>Template:Cite journal</ref>

The first attempted laboratory synthesis was made in 1924 by German chemist Hans Meerwein using the reaction of formaldehyde with diethyl malonate in the presence of piperidine. Instead of adamantane, Meerwein obtained 1,3,5,7-tetracarbomethoxybicyclo[3.3.1]nonane-2,6-dione: this compound, later named Meerwein's ester, was used in the synthesis of adamantane and its derivatives.<ref>Template:Cite journal</ref> D. Bottger tried to obtain adamantane using Meerwein's ester as precursor. The product, tricyclo-[3.3.1.1^3,7], was not adamantane, but a derivative.<ref>Coffey, S. and Rodd, S. (eds.) (1969) Chemistry of Carbon Compounds. Vol 2. Part C. Elsevier Publishing: New York.</ref>

Other researchers attempted to synthesize adamantane using phloroglucinol and derivatives of cyclohexanone, but also failed.<ref name="cr64">Template:Cite journal</ref>

File:Meerweins Ether.png

Meerwein's ester

Adamantane was first synthesized by Vladimir Prelog in 1941 from Meerwein's ester.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> With a yield of 0.16%, the five-stage process was impractical (simplified in the image below). The method is used to synthesize certain derivatives of adamantane.<ref Name="cr64" />

File:Adamantane synthesis by Prelog.png

Prelog's method was refined in 1956. The decarboxylation yield was increased by the addition of the Hunsdiecker pathway (11%) and the Hoffman reaction (24%) that raised the total yield to 6.5%.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> The process was still too complex, and a more convenient method was found in 1957 by Paul von Ragué Schleyer: dicyclopentadiene was first hydrogenated in the presence of a catalyst (e.g. platinum dioxide) to give tricyclodecane and then transformed into adamantane using a Lewis acid (e.g. aluminium chloride) as another catalyst. This method increased the yield to 30–40% and provided an affordable source of adamantane; it therefore stimulated characterization of adamantane and is still used in laboratory practice.<ref>Template:Cite journal</ref><ref>Template:OrgSynth</ref> The adamantane synthesis yield was later increased to 60%<ref name=app>Template:Cite book</ref> and 98% by ultrasound and superacid catalysis.<ref>Template:Cite book</ref> Today, adamantane is an affordable chemical compound with a cost of one or two USD per gram.

File:Adamantane synthesis.png

All the above methods yield adamantane as a polycrystalline powder. Using this powder, single crystals can be grown from the melt, solution, or vapor phase (e.g. with the Bridgman–Stockbarger technique). Melt growth results in the worst crystalline quality with a mosaic spread in the X-ray reflection of about 1°. The best crystals are obtained from the liquid phase, but the growth is impracticably slow – several months for a 5–10 mm crystal. Growth from the vapor phase is a reasonable compromise in terms of speed and quality.<ref name=lowt/> Adamantane is sublimed in a quartz tube placed in a furnace, which is equipped with several heaters maintaining a certain temperature gradient (about 10 °C/cm for adamantane) along the tube. Crystallization starts at one end of the tube, which is kept near the freezing point of adamantane. Slow cooling of the tube, while maintaining the temperature gradient, gradually shifts the melting zone (rate ~2 mm/hour), producing a single-crystal boule.<ref name=hard>Template:Cite journal</ref>

File:Adamantane spin.gif

Ball-and-stick_model, black carbon, white hydrogen

Natural occurrence

Adamantane was first isolated from petroleum by the Czech chemists S. Landa, V. Machacek, and M. Mzourek.<ref name=landa>Template:Cite journal</ref><ref>Template:Citation</ref> They used fractional distillation of petroleum. They could produce only a few milligrams of adamantane, but noticed its high boiling and melting points. Because of the (assumed) similarity of its structure to that of diamond, the new compound was named adamantane.<ref name = "cr64" />

Petroleum remains a source of adamantane; the content varies from between 0.0001% and 0.03% depending on the oil field and is too low for commercial production.<ref Name="msu_pr">{{#invoke:citation/CS1|citation |CitationClass=web }} Special practical problem for the students of IV year. Department of Petroleum Chemistry and Organic Catalysis MSU.</ref><ref name="bagriy_2">Template:Cite book</ref>

Petroleum contains more than thirty derivatives of adamantane.<ref Name="msu_pr" /> Their isolation from a complex mixture of hydrocarbons is possible due to their high melting point and the ability to distill with water vapor and form stable adducts with thiourea.

Physical properties

Pure adamantane is a colorless, crystalline solid with a characteristic camphor smell. It is practically insoluble in water, but readily soluble in nonpolar organic solvents.<ref Name="himicheskaya entsiklopediya">Template:Cite encyclopedia</ref> Adamantane has an unusually high melting point for a hydrocarbon. At 270 °C, its melting point is much higher than other hydrocarbons with the same molecular weight, such as camphene (45 °C), limonene (−74 °C), ocimene (50 °C), terpinene (60 °C) or twistane (164 °C), or than a linear C₁₀H₂₂ hydrocarbon decane (−28 °C). However, adamantane slowly sublimes even at room temperature.<ref name=j1/> Adamantane can be distilled with water vapor.<ref name="bagriy_2"/>

Structure

File:Adamantane angles bond-lengths.png

Bond lengths and angles of adamantane.

As deduced by electron diffraction and X-ray crystallography, the molecule has T_d symmetry. The carbon–carbon bond lengths are 1.54 Å, almost identical to that of diamond. The carbon–hydrogen distances are 1.112 Å.<ref name ="bagriy_1"/>

At ambient conditions, adamantane crystallizes in a face-centered cubic structure (space group Fm3m, a = 9.426 ± 0.008 Å, four molecules in the unit cell) containing orientationally disordered adamantane molecules. This structure transforms into an ordered, primitive, tetragonal phase (a = 6.641 Å, c = 8.875 Å) with two molecules per cell, either upon cooling to 208 K or pressurizing to above 0.5 GPa.<ref name="cr64"/><ref name=j1>Template:Cite journal</ref>

This phase transition is of the first order; it is accompanied by an anomaly in the heat capacity, elastic, and other properties. In particular, whereas adamantane molecules freely rotate in the cubic phase, they are frozen in the tetragonal one; the density increases stepwise from 1.08 to 1.18 g/cm³, and the entropy changes by a significant amount of 1594 J/(mol·K).<ref name=lowt/>

Hardness

Elastic constants of adamantane were measured using large (centimeter-sized) single crystals and the ultrasonic echo technique. The principal value of the elasticity tensor, C₁₁, was deduced as 7.52, 8.20, and 6.17 GPa for the <110>, <111>, and <100> crystalline directions.<ref name=hard/> For comparison, the corresponding values for crystalline diamond are 1161, 1174, and 1123 GPa.<ref>Template:Cite journal</ref> The arrangement of carbon atoms is the same in adamantane and diamond;<ref>Template:Cite book</ref> however, in the adamantane solid, molecules do not form a covalent lattice as in diamond, but interact through weak van der Waals forces. As a result, adamantane crystals are very soft and plastic.<ref name=lowt>Template:Cite journal</ref><ref name=hard/><ref>Template:Cite book</ref>

Spectroscopy

The nuclear magnetic resonance (NMR) spectrum of adamantane consists of two poorly resolved signals, which correspond to sites 1 and 2 (see picture below). The ¹H and ¹³C NMR chemical shifts are respectively 1.873 and 1.756 ppm and are 28.46 and 37.85 ppm.<ref name="sdbs">NMR, IR and mass spectra of adamantane can be found in the SDBS database Template:Webarchive</ref> The simplicity of these spectra is consistent with high molecular symmetry.

Mass spectra of adamantane and its derivatives are rather characteristic. The main peak at m/z = 136 corresponds to the Template:Chem ion. Its fragmentation results in weaker signals as m/z = 93, 80, 79, 67, 41 and 39.<ref name="bagriy_1"/><ref name="sdbs" />

The infrared absorption spectrum of adamantane is relatively simple because of the high symmetry of the molecule. The main absorption bands and their assignment are given in the table:<ref Name="bagriy_1" />

Wavenumber, cm−1	Assignment*
444	δ(CCC)
638	δ(CCC)
798	ν(C−C)
970	ρ(CH2), ν(C−C), δ(HCC)
1103	δ(HCC)
1312	ν(C−C), ω(CH2)
1356	δ(HCC), ω(CH2)
1458	δ(HCH)
2850	ν(C−H) in CH2 groups
2910	ν(C−H) in CH2 groups
2930	ν(C−H) in CH2 groups

^* Legends correspond to types of oscillations: δ – deformation, ν – stretching, ρ and ω – out of plane deformation vibrations of CH₂ groups.

Optical activity

Adamantane derivatives with different substituents at every nodal carbon sites are chiral.<ref>Template:Cite book</ref> Such optical activity was described in adamantane in 1969 with the four different substituents being hydrogen, bromine, methyl, and carboxyl. The values of specific rotation are small and are usually within 1°.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Nomenclature

Using the rules of systematic nomenclature, adamantane is called tricyclo[3.3.1.1^3,7]decane. However, IUPAC recommends using the name "adamantane".<ref name=iupac2013/>

File:Adamantane numbering.svg

The adamantane molecule is composed of only carbon and hydrogen and has T_d symmetry. Therefore, its 16 hydrogen and 10 carbon atoms can be described by only two sites, which are labeled in the figure as 1 (4 equivalent sites) and 2 (6 equivalent sites).

Structural relatives of adamantane are noradamantane and homoadamantane, which respectively contain one less and one more CH₂ link than the adamantane.

The functional group derived from adamantane is adamantyl, formally named as 1-adamantyl or 2-adamantyl depending on which site is connected to the parent molecule. Adamantyl groups are a bulky pendant group used to improve the thermal and mechanical properties of polymers.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Chemical properties

Adamantane cations

The adamantane cation can be produced by treating 1-fluoro-adamantane with SbF₅. Its stability is relatively high.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

The dication of 1,3-didehydroadamantane was obtained in solutions of superacids. It also has elevated stability due to the phenomenon called "three-dimensional aromaticity"<ref>Template:Cite book</ref> or homoaromaticity.<ref>Template:Cite journal</ref> This four-center two-electron bond involves one pair of electrons delocalized among the four bridgehead atoms.

File:Adamantane dication.png

Reactions

Most reactions of adamantane occur via the 3-coordinated carbon sites. They are involved in the reaction of adamantane with concentrated sulfuric acid which produces adamantanone.<ref>Template:Cite journal</ref>

File:Adamantanone synthesis.png

The carbonyl group of adamantanone allows further reactions via the bridging site. For example, adamantanone is the starting compound for obtaining such derivatives of adamantane as 2-adamantanecarbonitrile<ref>2-Adamantanecarbonitrile Template:Webarchive Organic Syntheses, Coll. Vol. 6, p. 41 (1988); Vol. 57, p. 8 (1977).</ref> and 2-methyl-adamantane.<ref>Template:Cite journal</ref>

Bromination

Adamantane readily reacts with various brominating agents, including molecular bromine. The composition and the ratio of the reaction products depend on the reaction conditions and especially the presence and type of catalysts.<ref Name="msu_pr"/>

File:Adamantane bromination.png

Boiling of adamantane with bromine results in a monosubstituted adamantane, 1-bromadamantane. Multiple substitution with bromine is achieved by adding a Lewis acid catalyst.<ref Name="nesmeyanov">Template:Cite book</ref>

The rate of bromination is accelerated upon addition of Lewis acids and is unchanged by irradiation or addition of free radicals. This indicates that the reaction occurs via an ionic mechanism.<ref Name="cr64" />

Fluorination

The first fluorinations of adamantane were conducted using 1-hydroxyadamantane<ref>Template:Cite journal</ref> and 1-aminoadamantane as initial compounds. Later, fluorination was achieved starting from adamantane itself.<ref>Template:Cite journal</ref> In all these cases, reaction proceeded via formation of the adamantane cation which then interacted with fluorinated nucleophiles. Fluorination of adamantane with gaseous fluorine has also been reported.<ref>Template:Cite journal</ref>

Carboxylation

Carboxylation of adamantane with formic acid gives 1-adamantanecarboxylic acid.<ref>Template:Cite journal</ref>

File:Adamantane caboxylic acid synthesis.png

Oxidation

1-Hydroxyadamantane is readily formed by hydrolysis of 1-bromadamantane in aqueous solution of acetone. It can also be produced by ozonation of the adamantane:<ref>Template:Cite journal</ref> Oxidation of the alcohol gives adamantanone.

File:1-Adamantanol synthesis.svg

Others

Adamantane interacts with benzene in the presence of Lewis acids, resulting in a Friedel–Crafts reaction.<ref>Template:Cite journal</ref> Aryl-substituted adamantane derivatives can be easily obtained starting from 1-hydroxyadamantane. In particular, the reaction with anisole proceeds under normal conditions and does not require a catalyst.<ref Name="nesmeyanov" />

Nitration of adamantane is a difficult reaction characterized by moderate yields.<ref>Template:Cite journal</ref> A nitrogen-substituted drug amantadine can be prepared by reacting adamantane with bromine or nitric acid to give the bromide or nitroester at the 1-position. Reaction of either compound with acetonitrile affords the acetamide, which is hydrolyzed to give 1-adamantylamine:<ref>Template:Cite journal</ref>

File:Preparation of amantadine.png

Uses

Adamantane itself enjoys few applications since it is merely an unfunctionalized hydrocarbon. It is used in some dry etching masks<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and polymer formulations.

In solid-state NMR spectroscopy, adamantane is a common standard for chemical shift referencing.<ref>Template:Cite journal</ref>

In dye lasers, adamantane may be used to extend the life of the gain medium; it cannot be photoionized under atmosphere because its absorption bands lie in the vacuum-ultraviolet region of the spectrum. Photoionization energies have been determined for adamantane as well as for several bigger diamondoids.<ref>Template:Cite journal</ref>

In medicine

All medical applications known so far involve not pure adamantane, but its derivatives. The first adamantane derivative used as a drug was amantadine – first (1967) as an antiviral drug against various strains of influenza<ref>Template:Cite journal</ref> and then to treat Parkinson's disease.<ref>Template:Cite book</ref><ref name="pmid15800186">Template:Cite journal</ref> Other drugs among adamantane derivatives include adapalene, adapromine, bromantane (bromantan), carmantadine, chlodantane (chlodantan), dopamantine, gludantan (gludantane), hemantane (hymantane), idramantone (kemantane), memantine, nitromemantine rimantadine, saxagliptin, somantadine, tromantadine, and vildagliptin. Polymers of adamantane have been patented as antiviral agents against HIV.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Dead linkTemplate:Cbignore</ref>

Influenza virus strains have developed drug resistance to amantadine and rimantadine, which are not effective against prevalent strains as of 2016.

• Adapalene structure.svg

  Adapalene

• Adapromine.svg

  Adapromine

• Amantadine.svg

  Amantadine

• Bromantane structure.svg

  Bromantane

• Memantine acsv.svg

  Memantine

• Rimantadine.svg

  Rimantadine

• Saxagliptin.svg

  Saxagliptin

• Tromantadine.svg

  Tromantadine

• Vildagliptin.svg

  Vildagliptin

In designer drugs

Adamantane was recently identified as a key structural subunit in several synthetic cannabinoid designer drugs, namely AB-001 and SDB-001.<ref>Template:Cite journal</ref>

Spacecraft propellant

Adamantane is an attractive candidate for propellant in Hall-effect thrusters because it ionizes easily, can be stored in solid form rather than a heavy pressure tank, and is relatively nontoxic.<ref name="ais">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Potential technological applications

Some alkyl derivatives of adamantane have been used as a working fluid in hydraulic systems.<ref Name="krugosvet">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Adamantane-based polymers might find application for coatings of touchscreens,<ref>Template:Cite journal</ref> and there are prospects for using adamantane and its homologues in nanotechnology. For example, the soft cage-like structure of adamantane solid allows incorporation of guest molecules, which can be released inside the human body upon breaking the matrix.<ref name=app/><ref>Template:Cite book</ref> Adamantane could be used as molecular building blocks for self-assembly of molecular crystals.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Adamantane analogues

Many molecules and ions adopt adamantane-like cage structures. Those include phosphorus trioxide P₄O₆, arsenic trioxide As₄O₆, phosphorus pentoxide P₄O₁₀ = (PO)₄O₆, phosphorus pentasulfide P₄S₁₀ = (PS)₄S₆, and hexamethylenetetramine C₆N₄H₁₂ = N₄(CH₂)₆.<ref>Template:Cite journal</ref> Particularly notorious is tetramethylenedisulfotetramine, often shortened to "tetramine", a rodenticide banned in most countries for extreme toxicity to humans. The silicon analogue of adamantane, sila-adamantane, was synthesized in 2005.<ref>Template:Cite journal</ref> Arsenicin A is a naturally occurring organoarsenic chemical isolated from the New Caledonian sea sponge Echinochalina bargibanti and is the first known heterocycle to contain multiple arsenic atoms.<ref>Template:Cite journal</ref><ref name=Bagno>Template:Cite journal</ref><ref name=Guella>Template:Cite journal</ref><ref>Template:Cite journal</ref>

• Adamantane acsv.svg

  Adamantane

• Hexamine.svg

  Hexamethylenetetramine

• Phosphorus-pentoxide-2D-dimensions.svg

  Phosphorus pentoxide

• Phosphorus-pentasulfide-2D-dimensions.png

  Phosphorus pentasulfide

• Tetramethylenedisulfotetramine.png

  Tetramethylenedisulfotetramine

• Tetrodotoxin.svg

  Tetrodotoxin

• Arsenicin A.png

  Arsenicin A

Conjoining adamantane cages produces higher diamondoids, such as diamantane (C₁₄H₂₀ – two fused adamantane cages), triamantane (C₁₈H₂₄), tetramantane (C₂₂H₂₈), pentamantane (C₂₆H₃₂), hexamantane (C₂₆H₃₀), etc. Their synthesis is similar to that of adamantane and like adamantane, they can also be extracted from petroleum, though at even much smaller yields.