Adamantane-l-carboxylic acid

To a stirred solution of [4-(2-pyrimidinyl)piperazino]ethylamine (2.0 g, 0.01 mol) in 50 ml of methylene chloride, adamantane-l-carboxylic acid chloride (3.6 g, 0.018 mol) and triethylamine (2.9 g, 0.015 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC. The residue was dissolved in ethyl acetate (10 ml) and subjected to flash chromatography using a 9 inch column of silica gel and ethyl acetate as the eluent. The N-[2-[4-(2-pyrimidinyl)-l-piperazinyl]ethyl]tricyclo[3.3.1.1(3,7)] decane-l-carboxamide was separated. 

A solution of 3-acetamino-adamantane-l-carboxylic acid (3.0 g) in 4 N sodium hydroxide (40 ml) was refluxed for 5 h. After cooling, the pH of the solution was adjusted to 7 with acetic acid. The crystalline precipitate was filtered off, washed with ethanol and dried to yield 2.20 g of the desired compound, melting point over 330°C. In order to purify the compound, 2.0 g of it was suspended in water (10 ml), 4 N NaOH (2 ml) was added, and the resulting solution filtered through a filter aid known under the registered trademark Dicalite. The filtrate was adjusted to a pH of 6.5 with acetic acid. The resulting crystalline precipitate was filtered off, washed with a little water followed by alcohol, and dried to yield 1.55 g of pure 3-amino-adamantane-l-carboxylic acid. 

Simple alcohols can be obtained from the decomposition of peroxy acids in cyclohexane or benzene at reflux. This chain reaction, which is efficient for adamantane-l-carboxylic acid (equation 40), is unfortunately usually complicated by side reactions involving hydrogen abstraction from the substrate or sol-... 

This explanation is supported by the inhibitory activities of the series of adamantanes shown in Figure 4. The simplest compound, adamantane-l-carboxylic acid, is a potent inhibitor, but introduction of a second carboxyl group results in substantially weaker inhibition. Activity is partially restored by the replacement of either or both carboxyl groups with acetic acid functions, in which the additional methylene groups may serve to reduce repulsive interactions. The inhibitory activity of these analogues thus emphasizes the importance of correct substituent orientation in the design of transition state analogues. 

Adamantane-l-carboxylic acid chloride [1, 15, before 1-Adamantyl chloroformatej. Mol. wt. 198.69, m.p. 54 -56°. Supplier A. 

Hydroxyl group Adamantane-l-carboxylic acid chloride. 0-Benzoylpropionic acid. Ethyl vinyl ether. 4-Methoxy-5,6-dihydro-2H-pyrane. p-Nitrophenyl chloroformate. 

Either direct or sensitized photolysis of 3-(V-phthalimido)adamantane-l-carboxylic acid leads to population of the triplet excited state, which decarboxylates in the presence of a base, giving V-(l-adamantyl)phthali-mide. The intermediate radical adds regiospecffically to electron deficient alkenes. This type of reaction can be extended to related compounds, where the electron donor (carboxylate) and the acceptor (phthalimide) are separated by a rigid spacer. The photodecarboxylation of phthalimides... 

Adamantane-l-carboxylic acid added with cooling at 5° to a mixture of 10%-oleum and 65%-nitric acid, then anhydrous formic acid added with vigorous stirring during 1.5 hrs., and stirring continued ca. 1 hr. adamantane-l,3-di-carboxylic acid. Y 83%. L. N. Butenko et al., Zh. Org. Khim. 9, 728 (1973) C. A. 79, 31565. 

Adamantane-1-carboxylic acid Homoadamantane-l-carboxylic acid MeOH or EtOH, Pt MeOH or EtOH, Pt 1-methoxy-, or 1-ethoxy-adamantane 1-methoxy-, or 1-ethoxy homo-adamantane 50 248, 255 a,b 255 c... 

A suspension of betamethasone (740.0 mg) in dioxan (20 ml) was treated with adamantane carboxylic acid (1.96 g) and trifluorcacetic anhydride (0.75 ml). The mixture was stirred at room temperature for 23 h during which time the steroid completely dissolved. Addition of sodium bicarbonate (2.0 g) and water gave a waxy semi-solid which was separated from the supernatant liquid by decantation. Water and a little methanol were added to the solid and the resulting granular material was removed by filtration and washed well with water. Fractional crystallization from methanol afforded adamantane carboxylic anhydride as the less soluble component and betamethasone 21-adamantane-l -carboxylate as the more soluble component. 

The introduction of the trimethylsilyl chloride trapping technique" led to improved yields in the case of simple aliphatic esters. The initial silylated products are easily isolated and can be converted into the acyloins simply and in high yield. For simple aliphatic esters the yields are in the range 56-92%. Use of trimethylsilyl esters, rather than simple alkyl esters, leads to faster reactions, but lower yields.Substituted esters which have been successfully used in the newer procedure include ethyl 2-ethylhexanoate (83%), ethyl trimethylsilylacetate (90%)," ethyl 3-trimethylsilylpropionate (65%)," ethyl phenylacetate (48%)," ethyl 3-phenylpropionate (79%)" and 2-(2-methoxycarbonylethyl)-2-methyl-l,3-dioxolane derived from levulinic acid (65%)." In the case of ethyl adamantane-l-carboxylate the yield using the newer procedure is reported to be inferior to that using the earlier procedure. 

Figure 3.25. The structure of P450cam complexed with a tether compound adamantane-1-carboxylic acid-5-dimethylaminonaphthalene-l-sulfonylamino-octyl-amide rendered as CPK atoms, PDB ILWL. The heme is rendered as a ball and stick figure. The tether compound occupies an open channel between helices F and G, helix B and the p-sheet domain with the fluorescein moiety residing on the surface and the adamantane moiety positioned in the substrate-binding site.

BrCeH4-CF2-CFaPh (vii) adamantano4 rboxylic or -dicarboxylic acids-t-SF4 - trifluoromethylated adamantanes - [replacement of bridgehead hydrogen by fluorine also occurs e.g., conditions for the conversion of adamantane-1 carboxylic acid into either a 15 1 mixture of l-(trifluoromethyl)adamantane and... 

Suitable model systems for the estimation of Cl should be free of the delocalized effect and should have a geometry closely resembling that of the meta-or para-substituted benzoic acids. There are two model systems that meet these requirements. They are the 3- and 4-substituted methyl benzoic acids, VI and VII and the 3-substituted adamantane-1-carboxylic acids, VIII, and 4-substituted bicyclo[2.2.2]octane-l-carboxylic acids(I). In both model systems, the delocalized effect is unimportant. The geometry of the substituted methylbenzoic acids is only approximately similar to that of the corresponding benzoic acids. The geometry of I is very similar to that of 4-substituted benzoic acids, as was noted previously that of VIII is fairly close to that of 3-substituted benzoic acids. 

Properties of Simple Adamantanes.—(+)-3-Ethyl-5-methyladamantane-l carboxylic acid, Mjig + 1.67°, has the (S) configuration (903) and (+)-l-amino-3-ethyl-5-methyladamantane the (S) configuration (904), ... 

Calixarenes, which are macrocyclic compounds, are one of the best building blocks to design molecular hosts in supramolecular chemistry [158]. Synthesis of calix[4]arenes, which have been adamantylated, has been reported [105, 109]. In calix[4]arenes, adamantane or its ester/carboxylic acid derivatives were introduced as substituents (Fig. 29). The purpose of this synthesis was to learn how to employ the flexible chemistry of adamantane in order to construct different kinds of molecular hosts. The X-ray structure analysis of p-(l-adamantyl)thiacalix[4]arene [109] demonstrated that it contained four CHCI3 molecules, one of which was located inside the host molecule cavity, and the host molecule assumed the cone-like conformational shape (Fig. 30). 

Reactant A R-l(2-hydroxy-ethyl)-pyrrolidine-2-carboxylic acid adamantan-2-ylamide (Fig. 10.2)... 

Adamantanecarboxylic acids with a carboxylic group at a bridgehead position, e.g. adaman-tane-1-carboxylic acid (8),111 react with sulfur tetrafluoride in the conventional way giving high yields of the corresponding trifluoromethyl-substituted adamantanes. l-(Trifluoromethyl)-adamantane (9) can also be formed in one step from adamantane by treatment with a mixture of sulfur tetrafluoride, hydrogen fluoride and formic acid the latter serves as a source of carbon monoxide. The reaction is believed to proceed via carbonylation of an intermediate carbocat-... 

Trifluoromethyl)adamantan-l-amine (17) is obtained in 50% yield from 3-aminoadaman-lane-1-carboxylic acid.115... 

Similar results are obtained with 2-adamantanol which rearranges to 1 -ada-mantanol (> 98 %) at 28°C in sulfuric acid. An equilibrium mixture containing small amounts of 2-adamantanol is rapidly achieved fromeither direction67 6 K This isomerization is one of the mechanistic bases for the preparation of ada-mantanone by the reaction of adamantane with sulfuric acid at 77°C (see Section V.A.l) 57> 67> 691. The Koch-Haaf carboxylation of 2-adamantanol similarly results in predominant 1-adamantyl carboxylic acid formation unless highly dilute reaction conditions are employed 57> 7°). 

Ifenprodil (= l-Methyl-2-hydroxy-2-(4-hydroxyphenyl) ethyl-1 -(4-benzyl-piperidine)] -(aryl piperidine) [at(/o-3-(Indol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane] (indolotropane) [Kynurenic acid (= 4-Hydroxy-2-quinolinecarboxylic acid)] (quinoline carboxylic acid) [Memantine (= 1-Amino-3,5 dimethyladamantane)] (amino adamantane, amino cyclic aliphatic) [Methadone (= 6-Dimethylamino-4,4-diphenyl-3-heptanone)] (aryl tertiary amine) [em/o-3-(l -Methylindol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane(indolotropane) exo- 3-( 1 -Methylindol-2-yl)-8-methyl-8-... 

Cinnamoyl- 6-CD (6-CiO-/3-CD) was sparingly soluble in water, although most 6-substituted 6-CDs are soluble. However, 6-CiO-/3-CD was solubilized in water on the addition of adamantane carboxylic acid or p-iodoaniline which could be included in a 6-CD cavity. These results suggest that 6-CiO-/l-CD formed supramolecular polymers in the solid state, as shown in the proposed structure in Fig. 17. The X-ray powder pattern of 6-CiO-/l-CD was similar to that of the complex between p-CD and ethyl cinnamate, in which /3-CDs formed a layer structure. The crystal structure of 6-aminocinnamoyl-/3-CD (6-aminoCiO-/l-CD) is shown in Fig. 12 and we discussed the relationship between crystal packing and the substituent group in Sect. 2.8. 

Carboxylic acids, such as adamantane-l,3,5,7-tetracarboxylic acid [43] and tetrapyr-idones (silane and carbon based) [44, 45], have been employed in the construction of 3-D diamondoid networks through self-complementary interactions, Scheme... 

Alkyl radicals that formed from alkanes under the action of various radical-like species can react rapidly not only with molecular oxygen, but can also be trapped by carbon monoxide. In this case, carboxylic acids can be obtained. Thus adamantane has been recently converted into 1-adamantanecarboxylic acid as the main product (Scheme II.7) [50]. N-Hydroxyphthalimide was used for this transformation as an efficient radical catalyst. The reaction occurs under mild conditions (CO pressure up to 15 atm and temperature below 100 °C) and gives l-adamantanecarboxyUc acid with selectivity 56% and conversion 75%. 

Figure 4 Some hydrogen-bonding patterns in crystalline carboxylic acids. The dimer motif is used in terephthalic acid, trimesic acid and adamantane-l,3,5,7-tetracarboxylic acid to obtain networks of increasing dimensionality...

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