Diethyl ether cyclization

Benzene- 1,2-diacetonitriles e.g. 19, in the presence of hydrogen bromide in acetic acid, or in diethyl ether, cyclize to 4-bromo-l //-3-benzazepin-2-amines, e.g. 20a.41,42 l//-Naphtho[2,3-t/]azepines, e.g. 22a, are prepared in a similar manner from naphthalene-2,3-diacetonitriles, e.g. 21.41 Replacement of hydrogen bromide by hydrogen iodide yields the corresponding 4-iodo derivatives, e.g. 20b and 22b. 

Cyclohexene 6 undergoes cyclization with hydrogen bromide in diethyl ether at 0 C to give l-bromo-6,7,8,9-tetrahydro-477-2-benzazepin-3-amine hydrobromide (7), rather than the alternative isomer, 3-broino-7,8,9,9a-tetrahydro-6//-2-bcnzazcpin-l-amine (8). 

When the chain bearing the allylsilane is one carbon longer, i.e., by the use of pentenylsilanes, cycloheptane rings can be formed. Both the (Z)- and (A )-isoiner of the (3-pentenyl)silanes can be synthesized selectively, but only the (Z)-(3-pentenyl)silane cyclized stereospecifically (complete 1,4-asymmetric induction). Both cthylaluminum dichloride and boron trifluoride diethyl ether complex promote the seven-membered ring formation35 43-48. 

The cyclization to the desired head-to-tail linked bis-benzimidazoles could also be performed utilizing aryl or alkyl isothiocyanates with N, N -dicyclohexylcarbodiimidc (DCC) [82]. Upon completion, the insoluble N,N -dicyclohexylthiourea formed had to be removed by filtration and the desired PEG-bound products were precipitated by the addition of diethyl ether. The results were essentially the same as those of the cyclizations with the above mentioned aldehydes. 

The linear isomer of 225, (E)-l,2,4,6,7-octapentaene (229), is formed in addition to other products on treatment of the bisdibromocarbene adduct to (E)-l,3,5-hexatriene with methyllithium in diethyl ether at -40 C like 226, it is a highly unstable hydrocarbon [90]. Several attempts to characterize the Z-isomer 230 [90, 91] also met with failure. Although very likely generated as an intermediate in these experiments, 230 immediately cyclized to o-xylylene (231), which can be trapped, e.g., as a Diels-Alder addition product. 

Nakagome and co-workers effected the successful cyclization of N-ethyl-N-arylaminomethylenemalonates (749) in poly phosphoric acid, prepared from orthophosphoric acid and phosphorus pentoxide in polyphosphate ester (PPE), prepared from phosphorus pentoxide and anhydrous diethyl ether in chloroform in phosphoryl chloride on the action of boron trifluoride etherate on the action of acetic anhydride and concentrated sulfuric acid or on the action of phosphorus pentoxide in benzene [71GEP2033971, 71JHC357 76JAP(K) 18440]. Depending on the work-up process, l-ethyl-4-oxoquinoline-3-carboxylates (750, R1 = Et), l-ethyl-4-oxoquinoline-3-carboxylic acids (750, R2 = H) and 3-ethoxycarbonyl-4-chloroquinolinium iodides (751) were obtained. Only the cyclization of... 

Aqui et al. investigated the cyclization of diethyl A-(3-substituted phe-nyl)aminomethylenemalonates (251) under different cyclization conditions (75JHC557). For cyclization, they applied a 4 7 mixture of concentrated sulfuric acid and acetic anhydride, polyphosphoric acid, polyphosphate (prepared from phosphorus pentoxide and diethyl ether in chloroform), phosphoryl chloride, and Dowtherm A (see Table VI). They found the most effective cyclization conditions were thermal cyclization (heating in Dowtherm A) and polyphosphate. 

Jones and Barteau [275] have studied the cyclization and related reactions of iodoethanol on Ag(llO). The mechanism of diethyl ether formation on Ag(llO) and its dependence on the coadsorbed oxygen species has been studied by Jones etal. [276]. 

Carbocyclic four-membered rings 2, 4 and 5 were formed in good yields on treatment of the a,diethyl ether.7 Interestingly, the corresponding dibromides did not undergo clean intramolecular cyclization under the same conditions.7... 

Cyclic oligomers with x - 2-9 are found to be present in poly(1,3-dioxolane) samples prepared by monomer-polymer-equilibrations using boron trifluoride diethyl etherate as catalyst. The molecular cyclization equilibrium constants 7fx are measured and the values are in agreement with those calculated by the Jacobson-Stockmayer theory, using an RIS model to describe the statistical conformations of the corresponding chains and assuming that the chains obey Gaussian statistics. 

Method A. A solution of the 3-allylglucose 56 (440 mg, 1.18 mmol) and tri-methylsilyl iodide (260 mg, 1.30 mmol) in 20 mL of dry benzene, under argon, was heated to 65°C. After 40 min, 20 mL benzene was added followed by the dropwise addition of a solution of tiibutyltin hydride (525 mg, 1.80 mmol) in 5 mL of benzene containing AIBN (35 mg, 60 mmol) over 2 h. After completion of the addition, the mixture was kept at 65°C for 1 h. The solvent was evaporated under reduced pressure, the residue was dissolved in 100 mL of diethyl ether, and the solution treated with 2 g of wet potassium fluoride for 10 h at 20°C. The mixture was filtered over silica gel, the solvent distilled off, and the remaining oil was flash chromatographed twice (first pentane-diethyl ether-dichloromethane, 55 35 10, then hexane-EtOAc, 7 3, Rf, 0.13) to give 195 mg (53%) of the cyclized products 58a and 58b. NMR spectroscopy showed a ratio of the exo-lendo-isomer 58a/58h of 9 1. 

Addition of propargyl chlorides to l -dienes.1 The homogeneous catalyst zinc chloride-diethyl ether effects the addition of propargyl chlorides to acyclic 1,3-dienes at low temperatures. The products undergo cyclization at higher temperatures. An example is the addition of the propargyl chloride (1) to isoprene (equation I). Similar reactions are obtained on reaction of 1 with 1,3-butadiene, piperylene, and 2,3-dimethyl-1,3-butadiene. 

When perfluoro-2-methylpent-2-ene reacts with amidine, the products may be vinylamidine, fluoropyrimidine, or hydroxypyrimidine depending on the reactivity of the amidine and on the presence of a catalyst as well as reaction time. In moderately polar media such as diethyl ether, the initial product is vinylamidine, promoting subsequent cyclization and dehydrofluorination the products of these transformations may be isolated and characterized. Meanwhile, other transformations occur with comparable rates. Therefore, the reaction in diethyl ether may not be used for the synthesis of fluoro-pyrimidines. However, hydroxypyrimidine may be obtained under these conditions with a yield of up to 60%. Analogous results were obtained when the reaction was conducted in Freon-113 (97IZY2024). 

Benzenetellurinyl trifluoroacetate converts olefins in the presence of acetonitrile, propionit-rile, or benzonitrile, in a reaction catalyzed by boron trifluoride-diethyl etherate to 2-acylamino-1-ethyl phenyl tellurium oxides. The mixture was then heated at 75° for 3 h to effect elimination of the phenyltelluro group and cyclization to the dihydrooxazole5. 

This result was confirmed and extended by Oliver and coworkers in a series of reports dealing with the intramolecular attack of a variety of organometallics7 (Al, Mg, Li, Zn, etc.) onto unactivated alkenes. When 4 was prepared from di(5-hexenyl)mercury, it cyclized to 5 in less than 1 h at 25 °C in diethyl ether and these cyclization reactions were thought to be promoted by metal-alkene complexation8, that required metals bearing empty orbitals. Moreover, the rate of cyclization is highly solvent-dependent at 25 °C 4 takes 8 days to cyclize in pentane, 96 h in benzene and less than an hour in diethyl ether. 

Diketone 12 must be condensed with a third, doubly functionalized octahydroacridine unit in the last step of the torand synthesis (cf Scheme 6.1). The following protocols (8-10) describe the three-step synthesis of torand precursor 15 from octahydroacridine 5. The reagents involved in these three steps are shown in Scheme 6.11. According to Protocol 8, octahydroacridine is condensed with benzaldehyde in the presence of acetic anhydride,24 as in the second stage of Protocol 2 (cf Scheme 6.3). The crystalline product 13 precipitates from the reaction mixture in high yield and purity. Ozonolysis of 13 (Protocol 9) is conducted by the method described in Protocol 7 for conversion of 11 to diketone 12 (cf. Scheme 6.10) and the same precautions apply. The product diketone 1425 requires no further purification after removal of benzaldehyde by trituration with diethyl ether. The third octahydroacridine unit is then readied for torand cyclization in Protocol 10 by condensing diketone 14 with Bredereck s reagent, r-butoxybis(dimethylamino)methane,26 which is commercially available. The bis[p-(dimethylamino)]enone product 15 is easily purified by precipitation from ether/dichloromethane. 

In the same way, substituted vinyl alcohols 93 are readily converted into 2-methyl-l,3,6-trioxocan propynyl-<2003RJ01384> or polyfluoroalkyl- <2002KGS1419> ethers (Equation 12), difficultly accessible by other methods. The cyclization is promoted by trifluoroacetic acid in boiling dry diethyl ether and affords high yields of the products. 

Reaction of AT-methy lene-ftrr-bu tvl.i in i n c with octafluoroisobutylene in diethyl ether in the presence of water leads to unexpected l,3,7-oxadiazocan-4-one ring system 155 as a result of the complex sequence of reactions (Scheme 39 <1996ZOB344>). It is believed to include steps of imine hydration, cyclization accompanied by elimination of tert-butylamine, and final hydrolysis of difluoromethyl moiety into carbonyl group. 

A new synthesis of dibenzoboroles by reductive cyclization of arylboron dibromides opens up access to several derivatives of this ring system (Scheme 6) <1996JA7981>. MonoaryIboron dibromides 61 and 62 were prepared by reaction of the appropriate aryl lithium compound 60 with boron tribromide in hexane. Reductive cyclization of arylboron dibromide 61 with an excess of lithium metal in diethyl ether gave bislithium dibenzoborole complex 63. At the time of writing, compound 63 was the first dibenzoborole dianion to be structurally characterized by X-ray... 

The important role played by the conditions of the halocyclization, and by the halogen employed, is evident in the cyclization of 2-hydroxy-6-[( )-l-propcnyl]cyclohexanecarboxylic acid (5), a precursor in the total synthesis of ( )-ramulosin2. When the iodolactonization is conducted with iodine and potassium iodide in aqueous sodium hydrogen carbonate, a mixture of 6/7/8 (X = 1) in a 14 57 29 ratio is obtained in 91 % yield, whereas a mixture of 6/7 in a 60 40 ratio and 86% yield is observed when the reaction is performed with iodine in diethyl ether/tetrahy-drofuran/aqueous sodium hydrogen carbonate. By contrast, the bromolactonizalion, carried out with bromine in methanol6, affords a 78 22 mixture of 6 and 7 (X = Br) in 88% yield. 

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