Cesium phenolates

For the preparation of the triazine membranes, the entire solid support (cellulose or polypropylene membrane) was treated with a 5 m solution of the corresponding amine in l-methyl-2-pyrrolidinone (NMP) and a 1 m solution of cesium phenolate in dimethyl sulfoxide (2 p L of each at one spot) and subsequently heated in a domestic microwave oven for 3 min. After washing the support successively with... 

Alkylation of cesium phenolates.3 Alkylation of hydroxylated 9,10-anthra-quinones can be accomplished fairly readily by alkylation of cesium phenolates. 

This instant invention represents an improvement in the Ullman coupling reaction. This investigation represents the first general method for coupling electron deficient phenols and unactivated aryl halides (1,2,3,4). The basis of the improvement lay in the high solubility of (CuOTf)2 benzene and cesium phenolate or copper phenolate in the reaction solvent, toluene. 

Cesium phenolates were introduced by Kellogg [16] for the synthesis of crown compounds, after crown ether diesters had been obtained in good yields from the cesium salts of aromatic carboxylic acids and oligoethylene glycol dihalides... 

The preparation of the crown ether 25 was achieved by reaction of the cesium phenolate 23 with the dibromo compound 24 in DMF without application of high dilution conditions [1]. The monoesters 28 were obtained in an analogous way be reaction of the cesium salicylate 26 with the bromides 27 (Fig. 2). 

A dramatic cesium effect was found by Weber in the case of the synthesis of the tetrabenzo crown ether 31, which is of interest for applications in ionselective electrodes [39]. The cyclization reactions starting from the cesium phenolate obtained from 29 and the tosylate 30 under high dilution conditions in DMF led to 31 in 37 % yield. This is a dramatic improvement of the formerly obtained yield of only 6 % in the system KOH/ -butanol/ethanol/DMF [40]. 

The NICS(O) values of the alkali phenolates increase down the group from —9.9 in Li, —9.2 in Na, —8.8 in K, —8.0 in Rb, —7.5 in Cs and —6.3 for free phenolate anion. Thus the charge localization is still effective for cesium phenolate, which has a more aromatic character than the free anion. The other criteria yield a similar pattern. The loss of aromaticity in the free phenolate anion, 60% of the neutral phenol, due to a p-jr delocalization discussed above, could largely be restored by ion pair formation with alkali metal cations, thanks to a charge localization effect of the latter. 

Decomposition with Bases. Alkaline decomposition of poUucite can be carried out by roasting poUucite with either a calcium carbonate—calcium chloride mix at 800—900°C or a sodium carbonate—sodium chloride mix at 600—800°C foUowed by a water leach of the roasted mass, to give an impure cesium chloride solution that is separated from the gangue by filtration (22). The solution can then be converted to cesium alum [7784-17-OJ, CS2SO4 Al2(S0 2 24H20. Extraction of cesium from the poUucite is almost complete. Solvent extraction of cesium carbonate from the cesium chloride solution using a phenol in kerosene has also been developed (23). 

Final alcohol precipitation not only allows for removal of the phenol and any remaining non-covalently bound hydrocarbon but also concentrates the DNA. Ribonuclease treatment removes any contaminating RNA. Additional purification by cesium chloride centrifugation (35) is also often performed. This is particularly suited to small quantities of DNA. Hydroxyapatite chromatography is also effective in separating RNA, proteins, and DNA (36.37). 

An 8000-member library of trisamino- and aminooxy-l,3,5-triazines has been prepared by use of highly effective, microwave-assisted nucleophilic substitution of polypropylene (PP) or cellulose membrane-bound monochlorotriazines. The key step relied on the microwave-promoted substitution of the chlorine atom in monochlorotriazines (Scheme 12.7) [35]. Whereas the conventional procedure required relatively harsh conditions such as 80 °C for 5 h or very long reaction times (4 days), all substitution reactions were found to proceed within 6 min, with both amines and solutions of cesium salts of phenols, and use of microwave irradiation in a domestic oven under atmospheric reaction conditions. The reactions were conducted by applying a SPOT-synthesis technique [36] on 18 x 26 cm cellulose membranes leading to a spatially addressed parallel assembly of the desired triazines after cleavage with TFA vapor. This concept was later also extended to other halogenated heterocycles, such as 2,4,6-trichloropyrimidine, 4,6-dichloro-5-nitropyrimidine, and 2,6,8-trichloro-7-methylpurine, and applied to the synthesis of macrocyclic peptidomimetics [37]. 

The selective alkylation of a chemically distinct phenohc site on a perfluorinated aromatic has been achieved following a polymer assisted solution phase protection of an alternative o-hydroxybenzoic acid unit as the dioxin-4-one (19) (Scheme 2.45) [66]. A diverse set of 22 different alkyl and benzyl bromides were then attached to the free phenol using cesium fluoride as the base, followed by treatment with Amberlyst 15 and Amberlyst A-21 as the work-up. Subsequent hydrolysis of the dioxin-4-one group with NaOH proceeded smoothly and was quenched... 

The etherification of support-bound phenols with alkyl halides is usually performed in dipolar aprotic solvents (DMF, NMP, DMSO) in the presence of bases such as DBU, KN(SiMe3)2, phosphazenes [149], or cesium carbonate (Entries 6 and 7, Table 7.11). 

Distribution of cesium in the batch tests remained constant within experimental error in addition, no third-phase formation was observed. The solvent concentrations of calix[4]arene-bis-(rm-octylbenzo-crown-6) and l-(2,2,3,3-tetrafluoroproproxy)-3-(4-sec-butylphenoxy)-2-propanol remained constant within experimental error. Solvent degradation with irradiation was evidenced by a decrease TOA concentration decrease and an degradation product (4-ver-butyl phenol) increase in the solvent phase. No decline in extraction or scrubbing performance of the irradiated solvents was observed. The stripping performance of the solvent was seriously impaired with irradiation however, a mild caustic wash and replenishment of the TOA concentration restored the ability to strip the irradiated solvent. 

Another phenoxide activating approach published by Buchwald et al. [18] is based on the reaction of cesium phenoxides with aryl bromides or iodides in the presence of catalytic amounts of copper(I) triflate and ethyl acetate in refluxing toluene (Scheme 3b). In certain cases equimolar amounts of 1-naphthoic acid have been added in order to increase the reactivity of the phenoxide. The authors assume the formation of a cuprate-like intermediate of the structure [(ArO)2Cu] Cs+ as the reactive species. In addition, diaryl ether formation between phenols and aryl halides has been achieved using a phosphazene base forming naked phenoxide in the presence of copper bromide in refluxing toluene or 1,4-dioxane [19]. 

Once cell wall breakage or enzymatic dissolution has occurred, a variety of procedures can be used for isolation and purification of the DNA. These generally rely on an initial deproteinization using phenol or a mixture of perchlorate, sarcosine, and chloroform-isoamyl alcohol.6 9 The crude DNA is further purified by enzyme treatments, alcohol precipitation and spooling, hydroxylapatite chromatography, cesium chloride gradient centrifugation, or any combination of these methods. 

Allyl bromide, methyl iodide and benzyl bromide are the triumvirate of common alkyl halides that alkylate metal alkoxides readily. In the case of phenols, potassium carbonate [Scheme 4.230]438 or cesium carbonate are competent bases whereas primary and secondary alcohols require potassium hydroxide [Scheme 4.231J,402 but the strongly basic conditions limit the scope of the method. For example, attempts to alkylate the secondary and phenolic hydroxyl groups of the intermediate 232.1 in a synthesis of the antibiotic Nogalamycin using the traditional metal alkoxide alkylation failed owing to competing sec-... 

In the series of the alkali metal carbonates and -hydroxides the cesimn compounds are the strongest bases [14]. For reasons of simpler handling the less hygroscopic carbonate is often preferred to the hydroxide. In dipolar aprotic solvents, carboxylic acids [15], phenols [16], thiols [17, 18] and sulfonamides [19] are easily deprotonated by cesium carbonate, whereas with carbamates such as e.g. benzyloxycarbonyl- ( Z -)protected amino acids no reaction occurs [20]. 

The application of cesium fluoride as base in the synthesis of crown compounds from phenols and the ditosylates of polyethylene glycols was first described by Reinhoudt [44]. This method uses the high basicity of weakly solvated ( naked ) fluoride anions under aprotic conditions and is based on the formation of very stable H—F bonds (approx. 569 kJ/mol, H—Cl approx. 432 kJ/mol for comparison) [8],... 

The applicability of cesium fluoride for the synthesis of smaller crown ether rings such as benzo[12]crown-4 (35) was investigated by Bartsch et al. [45]. The result of this study was that the 12-membered crown ether 35 and its naphthalene analogue 36 can be obtained from the aromatic diols 33 and the tosylate 34 with the base cesium fluoride in yields of 29 and 25 %, respectively. This means a significant increase in the 4% yield of benzo[12]crown-4 (35) reported by Pedersen, who started with sodium phenolate [38]. 

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