Pivaloyl chloride, reactions with

Figure 22. H NMR spectra in CDjCN solutions demonstrating reaction Scheme 13 (X = S). Upper [Fe,Sj(LS3) (SEt)P, formed by ligand substitution. Lower, cluster 37, formed by the indicated reaction using 1 equivalent of pivaloyl chloride. (Reproduced with permission from Ref. 33.)...

The we5 o-a-[o-[(carboxysuccinyl)amido]phenyl]-tris-a,a,a-[o-(pivalami-do)phenyl] porphyrin was synthesized by the reaction of tetrakis-a,a,a,a-(o-aminophenyl)porphyrin with a threefold excess of pivaloyl chloride, then with a large excess of succinyl chloride. The product was chromatographed on a silica gel column. The corresponding Fe(III) complex was obtained by the reaction with FeCls, and the methyl ester was hydrolyzed to yield the carboxylic acid derivative. 

Pivalates. The selective pivaloylation of sucrose with pivaloyl (2,2-dimethylpropionyl) chloride has been thoroughly investigated (56). The reactivity of sucrose toward pivaloylation was shown to be significantly different from other sulfonic or carboxyflc acid chlorides. For example, reaction of sucrose with four molar equivalent of toluene-/)-sulfonyl chloride in pyridine revealed, based on product isolation, the reactivity order ofO-6 0-6 > 0-1 > 0-2 (57). In contrast, a reactivity order for the pivaloylation reaction, under similar reaction conditions, was observed to be 0-6 0-6 > 0-1 > 0-4. 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Next, 25.3 g, 0.125 mol, of the above product are dissolved in 250 ml ethyl acetate and 0.125 mol perchloric acid as a 70% aqueous solution is slowly added thereto with continuous stirring. Then, an excess of pivaloyl chloride, 280 ml. Is added and the mixture slowly warmed to reflux temperature. The reaction mixture is refluxed for about 5 hours and allowed to cool to room temperature with continuous stirring. The product is precipitated as the perchlorate salt by the addition of perchloric acid, HCIO4, in 500 ml ether. The product is isolated and purified by dissolving in 75 ml acetone and precipitating it with 150 to 200 ml of water. 

In exceptional circumstances the acylium ion (or the polarised complex) can decompose to give an alkyl cation so that alkylation accompanies acylation. This occurs in the aluminium chloride-catalysed reaction of pivaloyl chloride which gives acylation with reactive aromatics such as anisole, but with less reactive aromatics such as benzene, the acylium ion has time to decompose, viz. 

Seebach and coworkers have developed the multiple coupling reagent, 2-nitro-2-propenyl 2,2-dimethylpropanoate (NPP). The reaction of nitromethane with formaldehyde gives 1,3-dihydroxy-2-nitropropane in 95% yield. Subsequent acylation with two equivalents of pivaloyl chloride and elimination of pivalic acid affords NPP. The reaction may be run on a 40- to 200-g... 

An alternative approach for the synthesis of 2, 3 -0,0-cyclic //-phosphonate 20a was based on the condensation of a mixture of uridine 3 - and 2 -//-phosphonates (23 and 24 respectively) induced by pivaloyl chloride (Scheme 9) [24], Its reaction with elemental sulfur in carbon disulfide gave 5 -0-DMT-uridine 2, 3 -cyclic phosphorothioate (21a) which after final deprotection afforded the desired 2, 3 -cyclic phosphorothioate 22a (Scheme 9). Its Sp and Rp diastereomers were separated by HPLC [24],... 

Polymer-supported glucal 37 was converted to the protected thioethyl glucosyl donor 39 as outlined in Scheme 2.11. Compound 37 was first epoxidized by the action of DMDO. The resulting 1,2-anhydrosugar was opened by a mixture of ethanethiol and dichloromethane (1 1) in the presence of a trace of trifluoroacetic acid. Polymer-bound 38 was thus obtained in 91% yield. This was a substantial improvement over the 78% yield obtained by the same protocol in solution. Protection by reaction with pivaloyl chloride occurred in quantitative yield to furnish 39a. 

The reaction of AK6-amino-4-quinazolinyl)aminomethylenemalonate (1460, R = NH2) and acyl chloride in methylene chloride in the presence of pyridine at 0°C afforded the 6-acylamido derivatives (1505) (81EUP30156). When the amine (1460, R = NH2) was repeatedly reacted with acetic anhydride in pyridine, the /V,/V-diacetylamino derivative (1506) was obtained. Treatment of the amine (1460, R = NH2) with pivaloyl chloride in methylene chloride in the presence of pyridine gave the pivaloylamido derivative (1505, R = Me3C—), while in DMF in the presence of pyridine a mixture of the pivaloylamido and 6-formamido derivatives (1505, R = Me3C— and H) was obtained. 

While attempting to prepare an T71-(vinylcarbene)iron complex121 by the alkylation or acylation of an a,/3-unsaturated acylferrate, Mitsudo and Wa-tanabe found122 that the major isolated product was in fact an -vinylketene complex (178), formed presumably by the carbonylation of an intermediate V-vinylcarbene, which may then undergo olefin coordination to the vacant metal site. All attempts to isolate such intermediates, or to observe them by 13C NMR spectroscopy, failed. Only in the reaction between potassium tetracarbonyl -cinnamoy ferrate (179.a) and pivaloyl chloride (180.b) was a side product (181) isolated in appreciable yield. In other reactions, only a trace (<1%) of such a compound was detected by spectroscopy. The bis(triphenylphosphine)iminium(l + ) (PPN) salts of 179.a and 179.b also reacted with 2 equiv of ethyl fluorosulfonate to give 178.g and 178.h in 21 and 37% yield, respectively. All products were somewhat unstable to silica gel, hence the low isolated yields in some cases. 

Comparison of the configuration of the stannane with the prodncts of reaction reveals that primary alkyl halides that are not benzyhc or a to a carbonyl react with inversion at the lithium-bearing carbon atom. In the piperidine series, the best data are for the 3-phenylpropyl compound, which was shown to be >99 1 er. In the pyrrolidine series, the er of the analogous compound indicates 21-22% retention and 78-79% inversion of configuration. Activated alkyl halides such as benzyl bromide and teri-butyl bromoacetate afford racemic adducts. In both the pyrrolidine and piperidine series, most carbonyl electrophiles (i.e. carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, cyclohexanone, acetone and benzaldehyde) react with virtually complete retention of configuration at the lithium-bearing carbon atom. The only exceptions are benzophenone, which affords racemic adduct, and pivaloyl chloride, which shows some inversion. The inversion observed with pivaloyl chloride may be due to partial racemization of the ketone product during work-up. 

The Richardson-Hough research partnership also observed that, if the quantity of pivaloyl chloride was raised to 7 equivalents and similar reaction conditions were applied, access to a partially pivaloylated trehalose having the 3- and 4 -hydroxyl groups free was gained in 38% yield, together with a symmetrical 2,3,6,2 3, 6 -hexapivalate, which was formed in 31% yield (Scheme 18). 

The establishment of the stereocenter in efavirenz provides a challenging goal for the synthetic chemist (Pierce et al., 1998 Thompson et al., 1995). The synthesis starts by treating 4-chloroaniline with pivaloyl chloride under biphasic conditions to provide the desired amide 10 (Scheme 6.2). Ortho metallation as directed by the amide is accomplished with two equivalents of n-butyllithium (or w-hexyllithium) in tetramethylethylene diamine (TMEDA) and MTBE. The resulting dianion is quenched with ethyl trifluoroacetate to provide pivaloylamide ketone 11 (Euhrer and Gschwend, 1979). The amide is hydrolyzed in situ to provide the trifluoroketone hydrate hydrochloride 12, which crystallizes from the reaction mixture (>98% pure). 

Reaction of cinnolin-4-amine with pivaloyl chloride yielded the expected corresponding amide as well as a disub-stituted compound resulting from the reaction of 4-pivaloylaminocinnoline with a second molecule pivaloyl chloride at N-1 <1995T13045>. Similarly, other amides have been made from 5-aminopyridazin-3(277)-ones... 

Less studied is another approach to derivatives of l-tellurocyclohex-3-ene 19 by which the first representatives of this heterocyclic system were obtained. It is also based on the Diels-Alder reaction, where trimethylsilyl telluropivaloate 20 is used as the dienophile (87CC820 92MI4). Compound 20 is formed, along with its isomer 20a, upon treatment of pivaloyl chloride with bis(trimethylsilyl) telluride, the 20/20a ratio being approximately 2 1. 

A closely related variant of this novel strategy has also been applied to the efficacious total syntheses of ( )-haemanthidine (382) and ( )-pretazettine (395) (209). In the event (Scheme 47), sequential reaction of the zinc derivative of the metalloenamine 509 with the protected amino acetaldehyde 516, pivaloyl chloride, and then 3 N HC1 provided an intermediate 8-keto aldehyde, which underwent cycloaldolization and dehydration on treatment with pyrrolidine in 33% aqueous AcOH-MeOH to furnish 517 as a mixture (1.5 1) of diastereo-mers. The a -bromination of 517 with PhNMe3Br3 in EtOAc followed by dehydrobromination with DBU in refluxing benzene then provided the racemic cyclohexadienone 518. Palladium(0)-catalyzed removal of the A-allyloxycar-... 

To a solution of 1 equivalent (eq.) of lH-tetrazole-1-acetic acid and 1 eq. of triethylamine in 20 ml of tetrahydrofuran cooled to -20°C was added 1 eq. of pivaloyl chloride. After thirty-minute stirring of the mixture 20 ml of a chloroform solution containing 1 eq. of and 1 eq. of triethylamine was poured into the solution cooled at -10°C during a period of 30 minutes. The resulting mixed solution was stirred for 30 minutes at the same temperature, for 1 hour in an ice-water mixture and for 3 hours at room temperature. Removal of a solvent from the reaction mixture afforded an oily residue, which was dissolved into 15 ml of 10% sodium bicarbonate aqueous solution. The resulting aqueous layer was adjusted to pH 1.0-2.0 with 10% hydrochloric acid, washed with ether and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and concentrated under reduced pressure leaving a residue which was triturated with ethyl acetate to obtain 3-acetoxymethyl-8-oxo-7-(2-tetrazol-l-acetylamino)-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

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