 | |||
| |||
 | |||
| Names | |||
|---|---|---|---|
| Preferred IUPAC name Adamantane[1] | |||
| Systematic IUPAC name Tricyclo[3.3.1.13,7]decane[2] | |||
| Identifiers | |||
| |||
3D model (JSmol) | |||
| 1901173 | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider |
| ||
| DrugBank | |||
| ECHA InfoCard | 100.005.457 | ||
| EC Number |
| ||
| 26963 | |||
| UNII | |||
| |||
| |||
| Properties | |||
| C10H16 | |||
| Molar mass | 136.238 g·mol−1 | ||
| Appearance | White to off-white powder | ||
| Density | 1.07 g/cm3 (25 °C)[2] | ||
| Melting point | 270 °C (518 °F; 543 K)[2] | ||
| Boiling point | Sublimes[2] | ||
| Poorly soluble | |||
| Solubility in other solvents | Soluble in hydrocarbons | ||
Refractive index (nD) | 1.568[2][3] | ||
| Structure | |||
| cubic,space group Fm3m | |||
| 4 | |||
| 0D | |||
| Hazards | |||
| Occupational safety and health (OHS/OSH): | |||
Main hazards | Flammable | ||
| GHS labelling: | |||
  | |||
| Warning | |||
| H319,H400 | |||
| P264,P273,P280,P305+P351+P338,P337+P313,P391,P501 | |||
| Related compounds | |||
Related compounds: | Memantine Rimantadine Amantadine | ||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Adamantane is anorganic compound with formula C10H16 or, more descriptively, (CH)4(CH2)6. Adamantane molecules can be described as the fusion of threecyclohexane rings. The molecule is both rigid and virtuallystrain-free. Adamantane is the most stable isomer of C10H16. The spatial arrangement ofcarbon atoms in the adamantane molecule is the same as in thediamond crystal. This similarity led to the nameadamantane, which is derived from the Greekadamantinos (relating tosteel ordiamond).[4] It is a white solid with acamphor-like odor. It is the simplestdiamondoid.
The discovery of adamantane inpetroleum 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.
In 1924, H. Decker suggested the existence of adamantane, which he calleddecaterpene.[5]
The first attempted laboratory synthesis was made in 1924 by German chemistHans Meerwein using the reaction offormaldehyde withdiethyl malonate in the presence ofpiperidine. 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.[6] D. Böttger tried to obtain adamantane using Meerwein's ester as precursor. The product was not adamantane, but a derivative with a tricyclo[3.3.1.13,7] ring system.[7][page needed]
Other researchers attempted to synthesize adamantane usingphloroglucinol and derivatives ofcyclohexanone, but also failed.[8]
Adamantane was first synthesized byVladimir Prelog in 1941 from Meerwein's ester.[9][10] With a yield of 0.16%, the five-stage process (simplified in the image below) was impractical for commerce. Prelog's method was refined in 1956. Thedecarboxylation yield was increased by the addition of the Hunsdiecker pathway (11%) and the Hoffman reaction (24%) that raised the total yield to 6.5%:[11][12]
The method is used to synthesize certain derivatives of adamantane.[8]
A more convenient method was found in 1957 byPaul von Ragué Schleyer:dicyclopentadiene was firsthydrogenated in the presence of a catalyst (e.g.platinum dioxide) to givetricyclodecane and then transformed into adamantane using aLewis 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.[13][14] The process is astonishingly robust: virtually any C10H16 alkane feedstock rearranges to adamantane in a strong Lewis acid.[15] The adamantane synthesis yield was later increased to 60%[16] and 98% byultrasound andsuperacid catalysis.[17] Today, adamantane is an affordable chemical compound with a cost of one or twoUSD per gram.
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 theBridgman–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.[18] 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-crystalboule.[19]
Adamantane was first isolated from petroleum by the Czech chemists S. Landa, V. Machacek, and M. Mzourek.[20][21][failed verification] They usedfractional distillation of petroleum. They could produce only a few milligrams of adamantane, but noticed its high boiling andmelting points. Because of the (assumed) similarity of its structure to that of diamond, the new compound was named adamantane.[8]
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.[22][23]
Petroleum contains more than thirty derivatives of adamantane.[22] 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 stableadducts withthiourea.
Pure adamantane is a colorless, crystalline solid with a characteristiccamphor smell. It is practically insoluble in water, but readily soluble in nonpolarorganic solvents.[24] Adamantane has an unusually highmelting point for ahydrocarbon. At 270 °C, its melting point is much higher than other hydrocarbons with the same molecular weight, such ascamphene (45 °C),limonene (−74 °C),ocimene (50 °C),terpinene (60 °C) ortwistane (164 °C), or than a linear C10H22 hydrocarbondecane (−28 °C). However, adamantane slowlysublimes even at room temperature.[25] Adamantane can bedistilled with water vapor.[23]
As deduced byelectron diffraction andX-ray crystallography, the molecule hasTd symmetry. The carbon–carbon bond lengths are 1.54 Å, almost identical to that of diamond. The carbon–hydrogen distances are 1.112 Å.[3]
At ambient conditions, adamantane crystallizes in a face-centered cubic structure (space group Fm3m,a = 9.426 ± 0.008Å, four molecules in the unit cell) containing orientationally disordered adamantane molecules. This structure transforms into an ordered, primitive,tetragonal phase (a = 6.641Å,c = 8.875Å) with two molecules per cell, either upon cooling to 208 K or pressurizing to above 0.5 GPa.[8][25]
Thisphase transition is of the first order; it is accompanied by an anomaly in theheat 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 theentropy changes by a significant amount of 1594 J/(mol·K).[18]
Elastic constants of adamantane were measured using large (centimeter-sized) single crystals and the ultrasonic echo technique. The principal value of theelasticity tensor, C11, was deduced as 7.52, 8.20, and 6.17 GPa for the <110>, <111>, and <100> crystalline directions.[19] For comparison, the corresponding values for crystalline diamond are 1161, 1174, and 1123 GPa.[26] The arrangement of carbon atoms is the same in adamantane and diamond;[27] however, in the adamantane solid, molecules do not form a covalent lattice as in diamond, but interact through weakvan der Waals forces. As a result, adamantane crystals are very soft and plastic.[18][19][28]
Thenuclear magnetic resonance (NMR) spectrum of adamantane consists of two poorly resolved signals, which correspond to sites 1 and 2 (see picture below). The1H and13C NMR chemical shifts are respectively 1.873 and 1.756 ppm and are 28.46 and 37.85 ppm.[29] The simplicity of these spectra is consistent with high molecular symmetry.
Mass spectra of adamantane and its derivatives are rather characteristic. The main peak atm/z = 136 corresponds to theC
10H+
16 ion. Its fragmentation results in weaker signals asm/z = 93, 80, 79, 67, 41 and 39.[3][29]
Theinfrared 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:[3]
| 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.
Adamantane derivatives with different substituents at every nodal carbon sites arechiral.[30] Such optical activity was described in adamantane in 1969 with the four different substituents beinghydrogen,bromine,methyl, andcarboxyl. The values ofspecific rotation are small and are usually within 1°.[31][32]
Using the rules of systematic nomenclature, adamantane is called tricyclo[3.3.1.13,7]decane. However,IUPAC recommends using the name "adamantane".[1]
The adamantane molecule is composed of only carbon and hydrogen and has Td symmetry. Therefore, its 16 hydrogen and 10 carbon atoms can be described by only two sites, which are labeled in the figure as1 (4 equivalent sites) and2 (6 equivalent sites).
Structural relatives of adamantane arenoradamantane andhomoadamantane, which respectively contain one less and one more CH2 link than the adamantane.
Thefunctional 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 bulkypendant group used to improve the thermal and mechanical properties of polymers.[33][34]
The chemistry of adamantane is dominated by the stability of thetertiary adamantanium cation, C10H+
15, itself isolable when treating 1‑fluoroadamantane with SbF5.[35][36]
Radical reactions of adamantane also occur preferentially at the bridgehead due to steric hindrance.[37]
Adamantanium's stability easesSN,1 substitution for 1‑adamantane derivatives. Thus 1‑bromoadamantane hydrolyzes in acid to 1‑hydroxyadamantane,[38] and the latter fluorolyzes to 1‑fluoroadamantane.[39] 1‑Hydroxyadamantane alsoalkylates activated arenes without a catalyst,[40] and the drugamantadine can be prepared in aRitter reaction withacetonitrile:[41]
With unsubstituted adamantane, strongBrønsted acids and other comparable electrophiles abstract ahydride equivalent from a bridgehead. For example,nitrosyl salts[42] oran applied voltage[43] oxidize adamantane to the cation intermediate. Under most conditions, the resulting adamantanium cation then attacks nearby nucleophiles, for a net substitution.Ozonation gives the alcohol:[38]
Of course, adamantane also reacts with less exotic reagents!
Various brominators, including molecularbromine, react via anionic pathway,[8] andsimilar reactions are possible with gaseousfluorine[44](butchlorination is likely a radical reaction).[45]The reaction products depend on the conditions, especially the presence and type ofcatalysis.[22]Boiling adamantane with bromine results in a monosubstituted adamantane, 1-bromadamantane. Multiple substitution is achieved with aLewis acid:[40]
The rate of bromination is accelerated upon addition of Lewis acids and is unchanged by irradiation or addition of free radicals.[8]
Adamantane undergoesKoch-Haaf carboxylation with formic acid to give1-adamantanecarboxylic acid...[46]
...and aScholl-type arylation withbenzene and acidic clay.[47]
Nitration of adamantane is a difficult reaction characterized by moderate yields. Direct nitration occurs best inglacial acetic acid.[48]
Adamantane oxidizes in concentratedsulfuric acid to2‑adamantanone:[49][50]
Even though the end product is unsubstituted at the bridgeheads, the latter are involved in the mechanism, which initially forms a bridgehead cation before undergoing intermolecular hydride transfer.[51]
Cations formed at a bridging carbon appear to equilibrate with a protoadamantyl cation: a ring expansion/contraction exchanges the roles of a neighboring bridgehead and the cationic center. Indeed, if an adamantane bridgehead carbon is substituted to stabilize a positive charge, then cation formation along the bridges causes asemipinacol rearrangement.[52] Such processes can be reversed to substitute at multiple bridging carbons at simultaneously.[53]
Thecarbonyl group of adamantanone is less reactive than most cyclic carbonyls, since (by symmetry) any adduct suffers fromaxial strain. Nevertheless, sufficiently reactive reagents (e.g.alkyllithiums instead ofGrignard reagents) allow further functionalization at the bridging site.[54] For example, adamantanone is the starting compound for 2-adamantanecarbonitrile[55] and 2-methyl-adamantane.[56]
Adamantane itself enjoys few applications since it is merely an unfunctionalizedhydrocarbon. It is used in somedry etching masks[57] andpolymer formulations.
Insolid-state NMR spectroscopy, adamantane is a common standard forchemical shift referencing.[58]
Indye lasers, adamantane may be used to extend the life of the gain medium; it cannot bephotoionized under atmosphere because its absorption bands lie in thevacuum-ultraviolet region of the spectrum. Photoionization energies have been determined for adamantane as well as for several biggerdiamondoids.[59]
All medical applications known so far involve not pure adamantane, but its derivatives. The first adamantane derivative used as a drug wasamantadine – first (1967) as anantiviral drug against various strains ofinfluenza[60] and then to treatParkinson's disease.[61][62] Other drugs among adamantane derivatives includeadapalene,adapromine,bromantane (bromantan),carmantadine,chlodantane (chlodantan),dopamantine,gludantan (gludantane),hemantane (hymantane),idramantone (kemantane),memantine,nitromemantinerimantadine,saxagliptin,somantadine,tromantadine, andvildagliptin.Polymers of adamantane have been patented as antiviral agents againstHIV.[63]
Influenza virus strains have developeddrug resistance to amantadine and rimantadine, which are not effective against prevalent strains as of 2016.
Adamantane was recently identified as a key structural subunit in several syntheticcannabinoiddesigner drugs, namelyAB-001 andSDB-001.[64]
Adamantane is an attractive candidate for propellant inHall-effect thrusters because it ionizes easily, can be stored in solid form rather than a heavy pressure tank, and is relatively nontoxic.[65]
Some alkyl derivatives of adamantane have been used as a working fluid inhydraulic systems.[66] Adamantane-based polymers might find application for coatings oftouchscreens,[67] and there are prospects for using adamantane and its homologues innanotechnology. 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.[16][68] Adamantane could be used as molecular building blocks for self-assembly of molecular crystals.[69][70]
Many molecules and ions adopt adamantane-like cage structures. Those includephosphorus trioxide P4O6,arsenic trioxide As4O6,phosphorus pentoxide P4O10 = (PO)4O6,phosphorus pentasulfide P4S10 = (PS)4S6, andhexamethylenetetramine C6N4H12 = N4(CH2)6.[71] Particularly notorious istetramethylenedisulfotetramine, often shortened to "tetramine", arodenticide banned in most countries for extreme toxicity to humans. The silicon analogue of adamantane, sila-adamantane, was synthesized in 2005.[72]Arsenicin A is a naturally occurringorganoarsenic chemical isolated from theNew Caledoniansea spongeEchinochalina bargibanti and is the first known heterocycle to contain multiple arsenic atoms.[73][74][75][76]
Conjoining adamantane cages produces higherdiamondoids, such asdiamantane (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.
The relateddication of 1,3-didehydroadamantane also has elevated stability due to the phenomenon called "three-dimensional aromaticity"[77] orhomoaromaticity.[78] Thisfour-center two-electron bond involves one pair of electrons delocalized among the four bridgehead atoms:
The retained names adamantane and cubane are used in general nomenclature and as preferred IUPAC names.
