Adamantane

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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 strain-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). 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.

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:

center|upright|frameless|class=skin-invert-image|Meerwein's ester

This compound, later named Meerwein's ester, was used in the synthesis of adamantane and its derivatives. D. Böttger tried to obtain adamantane using Meerwein's ester as precursor. The product was not adamantane, but a derivative with a tricyclo[3.3.1.1^3,7] ring system.

Other researchers attempted to synthesize adamantane using phloroglucinol and derivatives of cyclohexanone, but also failed.

Adamantane was first synthesized by Vladimir Prelog in 1941 from Meerwein's ester. 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. 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%:

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The method is still used to synthesize certain adamantane derivatives. The process is astonishingly robust: virtually any C₁₀H₁₆ alkane feedstock rearranges to adamantane in a strong Lewis acid. The adamantane synthesis yield was later increased to 60% and 98% by ultrasound and superacid catalysis. Today, adamantane is an affordable chemical compound with a cost of one or two USD 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 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.

thumb|[[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. 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.

Petroleum contains more than thirty derivatives of adamantane. 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.

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). The arrangement of carbon atoms is the same in adamantane and diamond; 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.

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. 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 ion. Its fragmentation results in weaker signals as m/z = 93, 80, 79, 67, 41 and 39. 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°.

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".

Chemical properties

The chemistry of adamantane is dominated by the stability of the tertiary adamantanium cation, C₁₀H, itself isolable when treating 1fluoro­adamantane with SbF₅.

Radical reactions of adamantane also occur preferentially at the bridgehead due to steric hindrance. For example, sulfoxidation gives exclusively 1-adamantanesulfonic acid.

Bridgehead reactions

Adamantanium's stability eases S_N,1 substitution for 1adamantane derivatives.

Thus 1bromo­adamantane hydrolyzes in acid to 1hydroxy­adamantane,

1Hydroxyadamantane also alkylates activated arenes without a catalyst,

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With unsubstituted adamantane, strong Brønsted acids and other comparable electrophiles abstract a hydride equivalent from a bridgehead.

For example, nitrosyl salts or an applied voltage 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:

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Adamantane also reacts with less exotic reagents.

Various brominators, including molecular bromine, react via an ionic pathway,

(but chlorination is likely a radical reaction).

The reaction products depend on the conditions, especially the presence and type of catalysis.

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The rate of bromination is accelerated upon addition of Lewis acids and is unchanged by irradiation or addition of free radicals.

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...and a Scholl-type arylation with benzene and acidic clay.

Nitration of adamantane is a difficult reaction characterized by moderate yields. Direct nitration occurs best in glacial acetic acid.

Substitution at bridging carbons

Adamantane oxidizes in concentrated sulfuric acid to 2adamantanone:

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Even though the end product is unsubstituted at the bridgeheads, they are mechanistically involved. A bridgehead cation forms initially before undergoing intermolecular hydride transfer.

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 a semipinacol rearrangement.

Such processes can be reversed to substitute at multiple bridging carbons at simultaneously.

The carbonyl group of adamantanone is less reactive than most cyclic carbonyls, since (by symmetry) any adduct suffers from axial strain. Nevertheless, sufficiently reactive reagents (e.g. alkyllithiums instead of Grignard reagents) allow further functionalization at the bridging site. For example, adamantanone is the starting compound for 2-adamantanecarbonitrile and 2-methyl-adamantane.

Uses

Adamantane itself enjoys few applications since it is merely an unfunctionalized hydrocarbon. It is used in some dry etching masks and polymer formulations.<!--seems uselessly vague-->

In solid-state NMR spectroscopy, adamantane is a common standard for chemical shift referencing.

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.

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 and then to treat Parkinson's disease. 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.

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

<gallery class="center" class=skin-invert-image>

File: Adapalene structure.svg|Adapalene

File: Adapromine.svg|Adapromine

File: Amantadine.svg |Amantadine

File: Bromantane structure.svg|Bromantane

File: Memantine acsv.svg|Memantine

File: Rimantadine.svg|Rimantadine

File: Saxagliptin.svg|Saxagliptin

File: Tromantadine.svg|Tromantadine

File: Vildagliptin.svg|Vildagliptin

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In designer drugs

Adamantane was recently identified as a key structural subunit in several synthetic cannabinoid designer drugs, namely AB-001 and SDB-001.

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.

Potential technological applications

Some alkyl derivatives of adamantane have been used as a working fluid in hydraulic systems. Adamantane-based polymers might find application for coatings of touchscreens, 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. Adamantane could be used as molecular building blocks for self-assembly of molecular crystals.

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. 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. 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.

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File: Adamantane acsv.svg|Adamantane

File: Hexamine.svg|Hexamethylenetetramine

File: Phosphorus-pentoxide-2D-dimensions.svg|Phosphorus pentoxide

File: Phosphorus-pentasulfide-2D-dimensions.png|Phosphorus pentasulfide

File: Tetramethylenedisulfotetramine.png|Tetramethylenedisulfotetramine

File: Tetrodotoxin.svg|Tetrodotoxin

File: Arsenicin A.png|Arsenicin A

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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.

The related dication of 1,3-didehydroadamantane also has elevated stability due to the phenomenon called "three-dimensional aromaticity" or homoaromaticity. This four-center two-electron bond involves one pair of electrons delocalized among the four bridgehead atoms:

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References