Triethyloxonium tetrafluoroborate

Of all the kinetic studies that have appeared Vofsi and Tobolsky (32) have carried out the most quantitative study. In their work they used 

They studied the rate as a function of both catalyst concentration and initial monomer concentration and obtained the results shown in Figs. 8, 9, and 10. Initial rates are directly proportional to initial monomer concentrations (Fig. 9). But as can be seen from Fig. 10 initial rates begin to deviate from linearity above a catalyst concentration of 2 x 10-2 mole/1. The rate of initiator disappearance was given by  

They found that the rate constant, kt in equation 38, was 1.3 to 1.7 X 10 2 for initial catalyst concentrations in the range 6.1 x 10 2 to 1.53 x 10-2 mole/1, [Me] of 2.62 mole/1, and [2170] of 6.1 mole/1. The data as a whole seemed to support the mechanism proposed above (Section IIIB1) for initiation with oxonium salts, namely  

Within a monomer concentration range of 4—10 mole/1 and a catalyst concentration below 3.0 X 10 2 moles/1, initiation is fast, and the initial rate is directly proportional to [70], Thus [7] is very small, and the rate is closely approximated by  

A plot of equation 43 is shown in Fig. 11. From it a value of kp of 0.2901/min mole (4.83 x 10-3l/mole sec) was deduced. Vofsi and Tobolsky conclude, however, that there is little doubt that to cover a wider kinetic range, two constants, namely kt and kp, are insufficient, and a termination term would have to be included to more fully describe the system. 

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Treatment of A -unsubstituted 1,4-oxazepinones 6 with triethyloxonium tetrafluoroborate, followed by sodium hydrogen carbonate, gives 5-ethoxy-l,4-oxazepines 8 via the salts 7 31... 

A solution of an oxazepinone 6 (0.100 g) and triethyloxonium tetrafluoroborate (1.5 mol equiv) in CH2C12 (10 mL) was stirred in an ice bath for 3 h and then diluted with CH2C12 (50 mL). The solution was washed successively with sat. aq NaHC03 and sat. brine, dried and evaporated in vacuo to give the products in 75-85 % yield as viscous yellow oils. The compounds are unstable and decompose on attempted chromatography. 

Successive treatment of the diazepinone 8 with triethyloxonium tetrafluoroborate and sodium hydrogen carbonate results in ethyl 5-ethoxy-l/f-l,4-diazepine-l-carboxylate (9).31... 

A solution of the diazepinone 8 (O.lOOg, 0.55 mmol) and triethyloxonium tetrafluoroborate (0.157 g, 0.83 mmol) in CH2C12 (10 mL) was stirred for 3h at 0 C and CH2C12 (50 mL) was then added. The solution was treated with sat. aq NaHC03, followed by brine, and the organic phase was separated, dried and evaporated to give the product yield 0.093 g (86%) yellow crystals (i-Pr20/hexane) mp 36.5-37 C. 

It is very interesting, however, that in alkane potassium diazoate alkylations with Meerwein s reagent (triethyloxonium tetrafluoroborate, Et30+BF4) in CH2C12 suspensions or with alkyl halides in hexamethylphosphoric triamide solutions, azoxy compounds (6.4) are formed, i.e., alkylation takes place at the (3-nitrogen (Moss et al., 1972). 

Neutral tertiary and secondary amides react with very reactive alkylating agents, such as triethyloxonium tetrafluoroborate, to give O-alkylation.63 The same reaction occurs, but more slowly, with tosylates and dimethyl sulfate. Neutralization of the resulting salt provides iminoethers. 

These reactions involve addition of the diazo ester to an adduct of the carbonyl compound and the Lewis acid. Elimination of nitrogen then triggers migration. Triethyloxonium tetrafluoroborate also effects ring expansion of cyclic ketones by ethyl diazoacetate.83... 

Some alkylations of ring nitrogen atoms are shown in Scheme 5. Study on alkylation of the [l,2,4]triazolo[5,l-cHl /lltriazine derivative 41 have been carried out by Chupakhin and co-workers <2002IZV1594>. The best result was obtained with triethyloxonium tetrafluoroborate as a reagent. The ethylation was found to proceed selectively on N-4 atom in the six-membered ring to result in formation of the quaternary salt 42. 

In the course of studies on the synthesis of [l,2,4]triazolo[3,4-A][l,2,4,5]tetrazines, Kotschy et al. investigated the alkylation of the morpholino derivative 13 of this ring system <2000ARK259>. It has been found that ethylation carried out with triethyloxonium tetrafluoroborate took place exclusively on the five-membered ring and yielded a mixture of 1-ethyl 14 and 2-ethyl 15 quaternary salts. 

A cyclized version, xilobam (S), is synthesized from ji-methylpyrrolidone by conversion to the imine (]) by sequential reaction with triethyloxonium tetrafluoroborate and then anhydrous ammonia. When this is reacted with 2,6-dimethyl-phenyl i socyanate, the centrally acting muscle relaxant xilobam (8) is formed. ... 

Triethyloxonium tetrafluoroborate also effects ring expansion of cyclic ketones by ethyl diazoacetate.36... 

Since the tertiary oxonium ion is the propagating species, preformed oxonium ions such as triethyloxonium tetrafluoroborate can be used for initiation (Eq. 7-28) [Meerwein et al., I960] ... 

The trialkyloxonium salts are powerful alkylating agents. Trimethyl- and triethyloxonium tetrafluoroborates, in particular, have been widely employed for methylation and ethylation of sensitive or weakly nucleophilic functional groups. Alkylations of over 50 such functional groups have been reported in the literature. Examples include amides,4,7,13 16 lac-... 

One of the major advantages of oxonium salts is that alkylations can be effected under reaction conditions that are generally much milder than those necessary with the more conventional alkyl halides or sulfonates. Triethyloxonium tetrafluoroborate, for example, has usually been employed at room temperature in dichloromethane or dichloroethane solution. Occasionally chloroform16-22 or no solvent at all4-20 is used. Difficult alkylations can be effected in refluxing dichloroethane.29 30 The less soluble trimethyloxonium tetrafluoroborate has been used as a suspension in dichloromethane or dichloroethane, or as a solution in nitromethane or liquid sulfur dioxide. Reports of alkylations in water23 and trifluoroacetic acid21 have also appeared. Direct fusion with trimethyloxonium tetrafluoroborate has succeeded in cases where other conditions have failed.25-30... 

Anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxides (4) are alkylated by triethyloxonium tetra-fluoroborate to give 5-ethoxy-1,2,3,4-triazohum tetrafluoroborates (35 Y = O) <88MRC1012, 91BAP265). Anhydro-5-thiolo-l,2,3,4-oxatriazolium hydroxides (5) are likewise alkylated with triethyloxonium tetrafluoroborate, but not with methyl iodide, producing the ethylthio derivatives... 

Corresponding thiatriazolium tetrafluoroborates (161 R = Ar) salts are formed by Meerwein alkylation (triethyloxonium tetrafluoroborate in methylene chloride) of the 5-olates (173) <76CC306>. This type of salt (161) generally serves as starting material for other types of mesoionic compound <76AHC(l9)i>. The l,2,3,4-thiatriazolium-5-olates (173) are reported to be stable towards acid hydrolysis while aryl azide is formed in boiling aqueous sodium hydroxide <76CC306>. 

The meso-ionic l,2,4-triazol-3-ones (200) are stable to acid, but alkaline hydrolysis gives 1,4-disubstituted semicarbazides. They do not normally participate in 1,3-dipolar cycloadditions, but the meso-ionic 1,4-diphenyl-l,2,4-triazol-3-one (200, R = R = Ph, R = H) and benzyne yielded 2-phenylindazole. 1,2,4-Triazolium salts (211) are formed with triethyloxonium tetrafluoroborate. Reduction of the meso-ionic compound 200, R = Me, R = R = Ph, with lithium aluminum hydride gives the triazolidinone 212. ... 

The meso-ionic 1,2,3,4-oxatriazoles (286) yield phenol by acidic hydrolysis, phenyl azide by alkaline hydrolysis, and the 5-ethyl 1,2,3,4-oxatriazolium cation with triethyloxonium tetrafluoroborate. The rearrangement 286 -> 288 is achieved with boiling ethanolic ammonia. 

Meso-ionic 1,2,3,4-tetrazol-S-ones (289) react with triethyloxonium tetrafluoroborate, 3rielding salts (294) that react with sodium sulfide in dimethylformamide, giving meso-ionic 1,2,3,4-tetrazole-S-thiones (295). ... 

Treatment of meso-ionic l,2,3,4-oxatriazole-5-thiones (286) (Section VII, I, 3) with boiling ethanoUc ammonia yields the isomers 297. These belong to a new class of meso-ionic heterocycle, which by O-alkylation with triethyloxonium tetrafluoroborate 3rield the salts 298, These are useful intermediates for the sjmthesis of a number of novel types of meso-ionic 1,2,3,4-thiatriazoles (299, 300, and 301). The l,2,3,4-thiatriazol-5-ones (297) have dipole moments in accord with their meso-ionic formulation. They are remarkably stable to acidic hydrolysis, and 1,3-dipolar cycloaddition reactions have not been observed alkaline hydrolysis yields aryl azides. 

The unsymmetrical 3,6-dialkoxy-2,5-dihydropyrazines are prepared via the jV-carboxyanhy-drides of the particular amino acid (e.g., 7) and subsequent reaction with the methyl ester of glycine or alanine to give the corresponding cyclodipeptides (e.g., 8). These hexahydrodioxopy-razines are converted to the 2,5-dialkoxy-3,6-dihydropyrazines by alkylation using Meerwein salts, such as trimethyloxonium tetrafluoroborate or triethyloxonium tetrafluoroborate n lb. 

O -Alkylations of azepin-2-ones, and benzazepin-2-ones, are most efficiently brought about by trialkyloxonium tetrafluoroborates (Meerwein s reagents) (B-69MI51600,73JOC1090, 81HCA373). S-Alkylation of the thiones is effected similarly. These oxonium salts have also proved useful for the alkylation of azepinedione precursors of azatropones and azatropolones (72JOC208) (see also Section 5.16.3.1.2). 5//-Dibenz[f>,e]azepine-6,11 -dione with triethyloxonium tetrafluoroborate O-ethylates at the amide carbonyl and not at the ketonic carbonyl as was first proposed (72AJC2421). 

Dibenz[f ,e]azepine-6,11 -dione and phosphorus pentachloride yield the 6-chloro derivative, ethanolysis of which furnishes the non-planar azatropone (129), identical to the product formed by ethylation of the dione with triethyloxonium tetrafluoroborate (72AJC2421). 

Triethyloxonium tetrafluoroborate in dichloromethane was used to convert the trimethylsilyl ether of a dioxopyrrolidine derived vinylcyclobutanol into a cyclohexanone 6 or a cyclo-hexenone 7.23 Rearrangement to five-membered rings competes with this ring enlargement and becomes the main reaction course on treatment with hydrochloric acid or boron trifluoride.23... 

The sulphur atom of alkyl(thioalkyl)phosphonium salts forms a new onium centre on triethyloxonium tetrafluoroborate alkylation in nitromethane848,849 (thiocetals see above). Phosphonium ketene acetals are potential alkylating agents for phosphorus dithioic acid anions in non-aqueous, aprotic and aqueous media and in phase-transfer catalysis conditions296 (reaction 263). It is suggested that onium ketene acetals react by nucleophilic attack on the methyl group of the acetal. 

Di-te/Y-butyl-4//-thiopyran (363) as well as its 4-methyl derivative 243 were readily aromatized to thiopyrylium salts 403 using trityl tetra-fluoroborate.286 2,4,6-Triphenyl-4//-thiopyran (45) (R = Ph) was analogously converted to salts 404 by the action of methyl iodide, dimethyl sulfate, triethyloxonium tetrafluoroborate,39 perchloric acid,362 or oxygen in acetic acid.363... 

Hydrolysis of nitriles.1 N itriles are converted to thioamides by reaction with I (2 equivalents) at 40° overnight. Under these conditions most other functional groups are stable. Kinetic studies indicate that the reaction with nitriles is a two-step process, the first of which is analogous to an enc reaction to give a. Thioamides arc particularly useful precursors to amines by the method of Borch (2, 430 431), reaction with triethyloxonium tetrafluoroborate followed by reduction withNaBHj..- ... 

In the course of O-alkylation with triethyloxonium tetrafluoroborate, the lactim ethers of 1,4-dihydro-3(2//)-isoquinoIinones were obtained (75JMC395). These are useful starting materials for reactions with amines resulting in 1,4-dihydro-3-isoquinolylamines (85EUP139296). By means of bifunctional amines, further condensed hetero-ring compounds could be synthesized (73JMC633). 

Oxadiazoles are difficult to alkylate. However, N-methylfurazinium salts are formed on heating furazans with dimethyl sulfate (74AJC1917,95JCS(P1)1083) the reaction is approximately 7 and 62 times slower, respectively, than the corresponding methylations of 1,2,5-thiadiazole and isoxazole. The N-ethyl salts of furazan itself and 3-phenylfurazan have been prepared using triethyloxonium tetrafluoroborate (64JA1863). 

The metallation of 3-methyl-4//-5,6-dihydro-l,2-oxazine has been shown to take place at the methyl group with hindered bases and at the methylene group with unhindered bases (81JA5916). Deprotonation of (753) with lithium dimethylamide at -65 °C followed by reaction with benzyl bromide gave (754) in 85% yield. This product was converted to enone (755) by reaction first with triethyloxonium tetrafluoroborate to produce an oxoiminium salt. The salt was stirred with trimethylamine and the resulting a,/3-unsaturated imine hydrolyzed with wet silica gel to the enone (Scheme 174). The lithiated derivative of (753) serves as a synthon for the unknown a-anion of methyl vinyl ketone. 

Whereas the reaction of the linearly fused 117/-pyrido[2,l -h]quina-zolin-ll-one (27) with alkylating agents (dimethyl sulfate at 120°C, and tri-ethyloxonium tetrafluoroborate in methylene chloride at 20°C) gave exclusively 7V(5)-alkylated quaternary salts (107), that of the isomeric angularly fused 6//-pyrido[l,2-a]quinazolin-6-one (28) with the soft methyl iodide afforded only the iV(5)-methyl quaternary iodide (108, X = I). The reactions of 28 with the hard dimethyl sulfate and triethyloxonium tetrafluoroborate yielded a mixture of 5-methyl-6-oxo-6//-pyrido[l,2-a]quinazolinium salts (108) and 6-alkoxypyrido[l,2-a]quinazolinium salts (109) (90JHC2005). 

The base-catalyzed alkylation of oxindoles favors C-alkylation, and O-alkylation is observed with halides only for particularly favorable intramolecular alkylations (B-70MI30614). Triethyloxonium tetrafluoroborate, on the other hand, gives the O-alkylated... 

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