18-crown synthesis

The ortho-xylyl unit may be considered as the synthetic complement of the catechol unit so often used in crown synthesis. This is especially so for the 1,2-bromomethyl compounds which may be used as electrophiles. These units have been incorporated in numerous crowns over the years and the syntheses are all quite similar. 

Pyrimidines have also served as electrophiles in crown synthesis from this group. 4,6-Dichloropyrimidine reacts with diethylene glycol and sodium hydride in anhydrous xylene solution to form the 20-crown-6 derivative as well as the other products shown in Eq. (3.48). Note that a closely related displacement on sy/rr-trichlorotriazine has been reported by Montanari in the formation of polypode molecules (see Eq. 7.5). 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

The principal variations on the normal crown synthesis methods were applied in preparing mixed crowns such as those shown in Eq. (3.55) and in forming isomers of the dibinaphthyl-22-crown-6 systems. The latter has been discussed in Sect. 3.5 (see Eq. 3.21) . The binaphthyl unit was prepared to receive a non-naphthyl unit as shown in Eq. (3.57). Binaphthol was allowed to react with the tetrahydropyranyl ether or 2-chloroethoxyethanol. Cleavage of the THP protecting group followed by tosyla-tion of the free hydroxyl afforded a two-armed binaphthyl unit which could serve as an electrophile in the cyclization with catechol. Obviously, the reaction could be accomplished in the opposite direction, beginning with catechol". ... 

Cesium Salts in Crown Synthesis 3.14 Organometallic Derivatives of Crowns... 

Benzoperaza-crown-3 cyclophanes, table, 710 Benzoperaza-crown-4 cyclophanes, table. 718 Benzoperaza-crown-4 cyclophanes (miscellaneous), table, 739 Benzoperaza-crown-5 cyclophanes. table, 741 Benzoperaza-crown-6 cyclophanes, table, 742 Benzoperaza-crown-8 cyclophanes, table. 748 Benzopolyaza-crown synthesis. 407 Benzotetraaza-crown macrocycles, table, 437 Benzotriaza-9-crown-3, 152 Benzotriaza-crown macrocycles, table. 437 A-Benzoyl protecting groups. 49. 63, 359, 552... 

A new, convenient, one-precursor crown synthesis proceeds from polyethylene glycol dibromides in the presence of barium hydroxide [equation (23)] half... 

The intramolecular bromo-alkoxylation shown in Scheme 53 is a new variant in crown synthesis and produces a bromomethyl crown ether. ... 

Diederich F, Jonas U, Gramlich V, Herrmann A, Ringsdorf H and Thilgen C 1993 Synthesis of a fullerene derivative of benzo[18]crown-6 by Diels-Alder reaction complexation ability, amphiphilic properties, and x-ray crystal structure of a dimethoxy-1,9-(methano[1, 2]benzomethano)fullerene[60] benzene clathrate Helv. Chim. Acta 76 2445-53... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

Simple and Complex Organic Molecules. Using modem direct fluorination technology, the synthesis of even the most complex perfluorocarbon stmctures from hydrocarbon precursors is now possible. For example, syntheses of the first perfluoro crown ethers, perfluoro 18-crown-6, perfluoro 15-crown-5, and perfluoro 12-crown-4 (54) have been reported. Perfluoro crown ethers (54,55) are becoming important as the molecules of choice for many F-nmr imaging appHcations (56) in humans and are particularly effective in brain and spinal diagnostics when... 

Chelation itself is sometimes useful in directing the course of synthesis. This is called the template effect (37). The presence of a suitable metal ion facihtates the preparation of the crown ethers, porphyrins, and similar heteroatom macrocycHc compounds. Coordination of the heteroatoms about the metal orients the end groups of the reactants for ring closure. The product is the chelate from which the metal may be removed by a suitable method. In other catalytic effects, reactive centers may be brought into close proximity, charge or bond strain effects may be created, or electron transfers may be made possible. 

H-Benzo[a]carbazole, 4,4a,5,l 1,1 la,l Ib-hexahydro-synthesis, 4, 283 Benzo[b]carbazole, N-acetyl-photochemical rearrangements, 4, 204 Benzo[/]chroman-4-one, 9-hydroxy-2,2-dimethyl-synthesis, 3, 851 Benzochromanones synthesis, 3, 850, 851, 855 Benzochromones synthesis, 3, 821 Benzocinnoline-N-imide ring expansion, 7, 255 Benzocinnolines synthesis, 2, 69, 75 UV, 2, 127 Benzocoumarins synthesis, 3, 810 Benzo[15]crown-5 potassium complex crystal stmcture, 7, 735 sodium complex crystal stmcture, 7, 735 Benzo[ 18]cr own-6 membrane transport and, 7, 756 Benzo[b]cyclohepta[d]furans synthesis, 4, 106 Benzocycloheptathi azoles synthesis, 5, 120... 

Fluorescent brightening agents, 1, 338-341 Fluoride ions nucleophilicity crown ethers and, 7, 756 Fluorides synthesis... 

Hexamine — see Hexamethylenetetramine 1,4,7,10,13,16-Hexaoxacyclooctadecane — see [18]Crown-6 Hexazinone as herbicide, 1, 187 Hex-2-enopyranoside, 2,3-dideoxy-synthesis, 1, 464 Hexobarbital, 3, 150 Hexogen, 3, 530 a-D-galacto- Hexopyranose nomenclature, 1, 31 Qf-D-ido-Hexopyranose nomenclature, 1, 31... 

Pyrido[2,3-c]cinnolines synthesis, 3, 242, 245 Pyrido[3,2-c]cinnolines synthesis, 3, 242, 245 Pyrido[3,4-c]cinnolines synthesis, 3, 242, 244, 245 Pyrido[4,3-c]cinnolines synthesis, 3, 242, 245 Py rido[ 18]crown-6 t-butylammonium complex... 

The compound known as 18-crown-6 is one of the simplest and most useful of the macrocyclic polyethers. Its synthesis in low yield was first reported by Pedersen. Greene and Dale and Kristiansen" have reported syntheses of the title compound from triethylene glycol and triethylene glycol di-p-toluenesulfonate. Both of these procedures use strong base and anhydrous conditions and achieve purification by more or leas classical methods. The combination of distillation and formation of the acetonitrile complex affords crown of high purity without lengthy chromatography or sublimation. ... 

The template effects of potassium and lithium ions are responsible for the efficiency of the synthesis of macrocyclic ligands in 18-CROWN-6 and2,2.7,7,12,12,17,l 7-OCTAMETHYL-21,22,23,24-TETRAOXAPER-HYDROQUATERENE. 

The diffusion, location and interactions of guests in zeolite frameworks has been studied by in-situ Raman spectroscopy and Raman microscopy. For example, the location and orientation of crown ethers used as templates in the synthesis of faujasite polymorphs has been studied in the framework they helped to form [4.297]. Polarized Raman spectra of p-nitroaniline molecules adsorbed in the channels of AIPO4-5 molecular sieves revealed their physical state and orientation - molecules within the channels formed either a phase of head-to-tail chains similar to that in the solid crystalline substance, with a characteristic 0J3 band at 1282 cm , or a second phase, which is characterized by a similarly strong band around 1295 cm . This second phase consisted of weakly interacting molecules in a pseudo-quinonoid state similar to that of molten p-nitroaniline [4.298]. 

Numerous other methods exist for making the simple crowns. Many of these methods are compared in Sect. 3.1 which deals with variations in the synthesis of 18-crown-6. Further commentary on the influence of templating ions on the synthesis of crown ethers may be found in Chap. 2, which deals with various aspects of the template effect. 

Many of the crown ether syntheses with which we are concerned in this book are one form or another of the Williamson ether synthesis. Although the simplest example of such a reaction would involve an co-haloethylene glycol oligomer which undergoes intramolecular cyclization, it is more common for two new bonds to be formed in crown syntheses. An early example of the formation of a crown by a double-Williamson can be found in Dale s synthesis of 18-crown-6. The rather obvious chemical steps are shown in Eq. (2.1). 

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