Tetrabutylammonium bromide phase transfer catalyst

The synthesis of anastrozole (Scheme 3.3) began with an 8 2 displacement of commercially available 3,5-fc (bromomethyl)toluene (19) using potassium nitrile and a phase-transfer catalyst, tetrabutylammonium bromide (Edwards and Large, 1990). The resulting fcw-nitrile 20 in DMF was then deprotonated with sodium hydride in the presence of excess methyl iodide to give the fc -dimethylated product 21. Subsequently, a Wohl-Ziegler reaction on 21 was carried out using A-bromosuccinamide (NBS), and a catalytic amount of benzoyl peroxide (BPO) as the radical initiator. Finally, an Sn2 displacement of benzyl bromide 22 with sodium triazole in DMF afforded anastrozole (2) as a white solid. 

Reagents and Equipment. Use the same apparatus as in Experiment [22A] for this synthesis. Weigh and add 150 mg (1.2 mmol) of 4-ethylphenol to the reaction vial followed by 250 xL of 25% aqueous sodium hydroxide solution ( ). Stir the mixture at room temperature until dissolution occurs. The phase-transfer catalyst (tetrabutylammonium bromide (Bu4N Br ), 15 mg, 0.05 mmol) is now added, followed by 90 xL (205 mg, 1.45 mmol) of methyl iodide. 

After dissolution of the sodium hydroxide, weigh arid add 150 mg of the phase-transfer catalyst, tetrabutylammonium bromide, followed by 2.05 g (900 jlL) of methyl iodide (in the hood) using an automatic delivery pipet ( h... 

DetkioketaKzation. Various thioacetals and thioketals are readily hydrolyzed by pyridinium bromide perbromide (1 equivalent) under phase-transfer conditions. Tetrabutylammonium bromide is used as catalyst and aqueous methylene chloride as solvent. The reaction is more efficient in the presence of pyridine as buffer. Yields are generally 75-90%.1... 

Alkynes.10 Alkynes can be prepared by double dehydrobromination of pic-dibromides in petroleum ether by use of powdered KOH and catalytic amounts of a phase-transfer catalyst. Tetraoctylammonium bromide, 18-crown-6, or even Aliquat 336 are much more effective than more hydrophilic quarternary ammonium salts, such as tetrabutylammonium hydrogen sulfate, previously used (7, 354-355)." Isolated yields are 80-98%. Yields are generally lower when mc-dichlorides are used as the starting material. 

The complex [ RhCl(l,5-COD) 2] and a phase transfer catalyst (cetyltrimethylammonium bromide or tetrabutylammonium hydrogen sulfate) also reduce aromatic hydrocarbons under hydrogen. ... 

Under phase transfer conditions (tetrabutylammonium bromide catalyst) butyl bromide was found to alkylate 2- and 4-hydroxypyridines at both O and N with alkylation at the latter predominating. A variety of alterations in reaction conditions (salts, solvent, temperature) did not profoundly affect the product distribution. This finding is in apparent contrast to the findings reported in section 15.4. 

Pha.se-Tra.nsfer Ca.ta.lysts, Many quaternaries have been used as phase-transfer catalysts. A phase-transfer catalyst (PTC) increases the rate of reaction between reactants in different solvent phases. Usually, water is one phase and a water-iminiscible organic solvent is the other. An extensive amount has been pubHshed on the subject of phase-transfer catalysts (233). Both the industrial appHcations in commercial manufacturing processes (243) and their synthesis (244) have been reviewed. Common quaternaries employed as phase-transfer agents include benzyltriethylammonium chloride [56-37-17, tetrabutylammonium bromide [1643-19-2] tributylmethylammonium chloride [56375-79-2] and hexadecylpyridinium chloride [123-03-5]. 

Similarly to classical PTC reaction conditions, under solid-liquid PTC conditions with use of microwaves the role of catalyst is very important. On several occasions it has been found that in the absence of a catalyst the reaction proceeds very slowly or not at all. The need to use a phase-transfer catalyst implies also the application of at least one liquid component (i.e. the electrophilic reagent or solvent). It has been shown [9] that ion-pair exchange between the catalyst and nucleophilic anions proceeds efficiently only in the presence of a liquid phase. During investigation of the formation of tetrabutylammonium benzoate from potassium benzoate and tetrabu-tylammonium bromide, and the thermal effects related to it under the action of microwave irradiation, it was shown that potassium benzoate did not absorb micro-waves significantly (Fig. 5.1, curves a and b). Even in the presence of tetrabutylammonium bromide (TBAB) the temperature increase for solid potassium benzoate... 

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

In a 500 ml flat-bottomed three-necked flask, equipped with a powerful stirrer, dropping funnel, nitrogen inlet,and bubble counter are placed successively 0.93 g (5 mmol) of bisphenol A, 1.0 g of tetrabutylammonium bromide (phase transfer catalyst), and... 

Alkylation of 2,4-disubstituted-5(477)-oxazolones can be conveniently performed via phase-transfer catalysis. For example, the substrate and an alkyl halide are dissolved in an organic solvent and stirred with an aqueous sodium carbonate solution containing tetrabutylammonium bromide as a phase-transfer catalyst. 4,4-(Diarylmethyl)-2-phenyl-5(4/f)-oxazolones can be prepared in one-step by dialkylation of 146 using magnesium methyl carbonate and the corresponding... 

A potential way to avoid the formation of undesired side products, like in 7.2., is the use of such boron compounds that have only one transferable group. In most cases boronic acids are the compounds of choice, as they are easy to prepare, insensitive to moisture and air, and usually form crystalline solids. In certain cases, however the transmetalation of the heteroaryl group might be hindered by the formation of stable hydrogen bonded complexes. In such cases the use of a boronate ester, such as in equation 7.4., provides better yields. For example pyridine-2-boronic acid dimethylester coupled readily with a bromoquinoline derivative under conditions similar to 7.3. (potassium hydroxide was used as base and tetrabutylammonium bromide as phase transfer catalyst).6... 

The use of mixtures of sodium hydroxide and benzyltrimethylammonium chloride or tetrabutylammonium bromide failed to enhance the DPGE alkylation of HEC by the in situ formation of the corresponding quaternary ammonium hydroxide phase transfer catalyst. These quaternary ammonium halides are too soluble in aqueous /-butyl alcohol and are preferentially extracted into the organic phase. Mixtures of benzyltrimethylammonium hydroxide and sodium acetate were also ineffective in enhancing the DPGE alkylation of HEC for the same reason, namely preferential solubility of benzyltrimethylammonium acetate in the organic phase. 

Upon facing the difficulty of stereochemical control in peptide alkylation events, Maruoka and coworkers envisaged that the chiral phase-transfer catalyst should play a crucial role in achieving an efficient chirality transfer, and consequently examined the alkylation of the dipeptide, Gly-L-Phe derivative 57 (Scheme 5.28) [31]. When a mixture of 57 and tetrabutylammonium bromide (TBAB, 2 mol%) in toluene was treated with a 50% KOH aqueous solution and benzyl bromide at 0°C for 4h, the corresponding benzylation product 58 was obtained in 85% yield with the diastereo-meric ratio (DL-58 LL-58) of 54 46 (8% de). In contrast, the reaction with chiral quaternary ammonium bromide (S,S)-lc under similar conditions gave rise to 58 with 55% de. The preferential formation of LL-58 in lower de in the reaction with (R,R)-lc indicated that (R,R)-lc is a mismatched catalyst for this diastereofacial differentiation of 57. Changing the 3,3 -aromatic substituent (Ar) of the catalyst 1 dramatically increased the stereoselectivity, and almost complete diastereocontrol was realized with (S,S)-lg. 

Benzylations reaction using TBAB (tetrabutylammonium bromide) as a phase-transfer catalyst in glass microchannel reactors has been investigated as well [215], A dichloromethane/aqueous biphasic system was used in which both the substrate... 

A new cyclization process was published in 2003 <2003PS1295>, where dithiols are substituted by dithioiminium salts, which can be created by reacting thioacteamide 5 with a,o -dihalides. In a second step, the dithioiminium salts 6 are treated with (different) a,tu-dihalides adding sodium hydroxide, as base, and tetrabutylammonium bromide, as phase-transfer catalyst (Scheme 2). Thus, two kinds of macrocycles are found in the final reaction mixture XS2 (1 1 ratio) 7 and (2X)S4 (2 2 ratio) 8. 

Methylthiopyridine was prepared in this two phase system using tetrabutylammonium bromide as the phase transfer catalyst. 

MeTHF has also been used as an alternative to dichloromethane in biphasic reactions including alkylations, amidations and nucleophilic substitutions. For example, 2-nitrophenyl phenyl ether was prepared in 95% yield using 2-MeTHF as the organic solvent through reaction of phenol and o-fluoronitrobenzene using tetrabutylammonium bromide as a phase transfer catalyst. 

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