Phenacyl bromides, reaction with

The course of the reaction of phenacyl bromides (39) with nickel carbonyl is markedly dependent on the solvent employed in tetrahydrofuran the products are 1,2-dibenzoylethanes (cf. 40) but in dimethylformamide, 2,5-diarylfurans (41) are obtained in moderate to excellent yield (Scheme 53).90 It is possible that the furan derivatives (41) arise via intermediate fi,y-epoxyketones which can be isolated as products from a number of a-bromo-ketone substrates [cf. 39 and Section II].28... 

It appears that treatment of phenacyl bromides 1239 with methylhydrazine in refluxing acetic acid leads also to 1,4-disubstituted triazoles 1244. Fivefold excess of methylhydrazine is used in these reactions. According to the proposed mechanism, structures 1240-1243, methylhydrazine has a double role, as a condensing agent and an oxidant. In the final account, three molecules of methylhydrazine have to be used to produce one molecule of triazole 1244, two molecules of methylamine and one molecule of ammonia. The basic triazole 1244 (X = Y = H) is separated in 59% yield. The reactions go well with electron-donating substituents (for X = OH, the yield is 81%), but electron-withdrawing substituents can lower the yield dramatically (11% for X = N02) (Scheme 206) <2003JCM96>. 

The classic Krohnke aldehyde synthesis results from the displacement of pyridinium salts aromatic nitroso compounds to give nitrones which are hydrolyzed to aldehydes.Phenacyl bromide reacts with pyridine and then nitrosobenzene to give phenylglyoxal in 76% yield after acid hy lysis. The pyridinium salts in these reactions must be activated in some way toward displacement to effect efficient conversions. 

There is continumg interest in the organometalhc chemistry of Pd. This oxidation state has often been invoked as an intermediate in the reactions of Pd species with reactive acyl or alkyl halides. Spectroscopic evidence has been obtained for this hypothesis. When phenacyl bromide reacts with dimethylpalladium(n) complexes, such as PdMe2(bpy), a complex can be isolated at 0 °C, which is shown, by H NMR and X-ray crystallography, to be PdBrMe2(CH2COAr)(bpy) (equation 2). The same complex reacts with Mel to form PdIMe3(bpy). The d Pd complexes are expected to exhibit... 

Condensation of a-haloketones. a-Haloketones react with acid chlorides and anhydrides to afford p-diketones when the reaction is promoted by Smlj (14 examples, 71 -90%). Similarly, aldol condensation occurs with aliphatic a-diketones, while phenacyl bromide condenses with aldehydes if EtjAlCl is present. ... 

In the reaction of phenacyl bromides 244 with A-methylthiosemicarbazide, nucleophilic amino-debromination is accompanied by condensation of the 0x0 and hydrazono groups, followed by aromatization into triazines 245 (Scheme 146) <2004SOS(17)357>. 

Likewise, Kishan and Sundaram (1985, 1980) report that substituted phenacyl bromides (CgHjCOBr) are oxidized (in 40-70% acetic acid/H2S04) without complex formation. The reaction is catalyzed by acid, but the pseudo-first-order fits depend on the initial [Ce(lV)]. This observation is attributed to the presence of an unreactive Ce(IV) trimer, which has been reported to be present in acetic acid solutions. The rate of reaction of phenacyl bromides substituted with either electron-withdrawing or electron-donating substituents is faster than that of unsubstituted phenacyl bromide. The activation parameters for the p-methyl and p-methoxyl substituents suggest that a different mechanism operates for these systems. Where comparable substituents exist, the rates for oxidation of phenacyl bromides compare favorably with those for benzaldehyde dted above. 

In 1937, Kondo and Nagasawa confirmed the reactivity of the sole 2-methyl group in the condensation of 2,4-dimethylthiazole with benzal-dehyde (505) and in the cyclizafion to tbiazolopyrrole in the reaction with phenacyl bromide (506) (Scheme 113). 

The rates of reaction of phenacyl bromide with thiosemicarbazide and its phenylated derivative were determined by conductivity measurements in ethanol (517). The reaction is second order up to 85% completion. The activation energies are 10.5 to 11.3 kcal/mole with the phenyl thiosemicarbazide and 8.5 to 9.3 kcal/mole for the unsubstituted derivatives. 

The reaction with the oxime of phenacyl bromide is much slower than that of the parent ketone itself. Hammett s correlation applicated to these reactions gave p = 0.63 and 0.74 for 141, R, = Ph and Rj = H, respectively (517). 

Thiopyrones and selenopyrones can be alkylated more readily than pyrones. Thus 2,6-dimethyl-4/f-pyran-4-thionc (4,6-dimethyl-4-thiopyrone) (23, Y = S) reacts rapidly with methyl iodide yielding a 4-methylmercaptopyrylium iodide (24, Y = S, R = Me, X = I). Many alkylating agents were investigated by King et al. The kinetics of the reaction between 2,6-dimethyl-4-thiopyrone and substituted phenacyl bromides was found to be described by the Hammett... 

Alternatively, the thiazolotriazine ring was prepared from l-nitro-2-aminonaphthalene with an isothiocyanate to give naphthylpyrimidine 669, whose reaction with phenacyl bromide gave thiazoline 670. Reduction with stanous chloride and cyclization with (V-bromosuccinimide gave naphthothiazolotriazine 671 (74JIC631) (Scheme 138). 

A carboxylic acid (not the salt) can be the nucleophile if F is present. Mesylates are readily displaced, for example, by benzoic acid/CsF. Dihalides have been converted to diesters by this method. A COOH group can be conveniently protected by reaction of its ion with a phenacyl bromide (ArCOCH2Br). The resulting ester is easily cleaved when desired with zinc and acetic acid. Dialkyl carbonates can be prepared without phosgene (see 10-21) by phase-transfer catalyzed treatment of primary alkyl halides with dry KHCO3 and K2C03- ... 

Another cyclisation involving 4-amino-6-methyl-3-thioxo-l,2,4-tiiazin-5-one 82 is the reaction with propargyl bromide followed by palladium(II) catalysis to yield a [1,2,4] triazino[3,4-f ][l,3,4]thiadiazine 83, or with phenacyl bromide to give 84 <96MI03 96CA(125)195597 96MI04 96CA(125)247767 >. 

Rap-Stoermer reactions are useful for the preparation of 2-benzoylbenzofuran derivatives (91) by a base-assisted condensation of salicylaldehydes (89) with phenacyl bromides (90) (Scheme 15). However, these reactions are not very... 

Correlation analyses of this type have also been carried out in connection with the kinetics of the reaction of arfha-substituted benzoate ions with para-substituted phenacyl bromides and of ortho-substituted benzoate ions with ethyl bromoacetate. In all cases it is possible to include o-S02Me among the basic set of well-behaved substituents. 

Alkyl-8H-7-aryl-l,2,4-triazino[3,4-3]-[l,3,4]thiadiazine-4-oncs 19 have been prepared from the reactions of tri-azines 30 with various phenacyl bromides. The intermediates 31 formed in such reactions underwent loss of HzO to form 19 (Scheme 2) <2003CHE809>. 

The indolo analogue 25 was prepared (86AP659) by alkylation of 9-methyl-3,4-dihydro-/3-carboline 23 with phenacyl bromide followed by perchloric acid to give 24. Reaction of 24 with hydrazine hydrate gave triazinopyridoindole 25, which underwent 1,126-dehydrogenation with Hg(II)-EDTA (86AP659). 

Cyclization of the hydrazinoquinazolines 424 was also effected (91MI5, 91MI7) by reaction with 4-substituted phenacyl bromides to give [1,2,4] triazino[4,3-a]quinazolines 429. 

Cyclocondensation of 754 with phenacyl bromide gave (86JHC721) 3-phenyl-7,7,11 -trimethyl-8//-benzopyrano[4,3-e]imidazo[ 1,2-b] [1,2,4]-triazine 755. Cyclization of the 3-hydrazino derivative 756, with formic acid gave 757. Compounds 754 and 756 were prepared by reaction of the triazinobenzopyrane 753 with phosphorus oxychloride, followed by amination or hydrazinolysis (86JHC721). 

Cyclocondensation of pyrido[2,l-/][l,2,4]triazine 789 with phenacyl bromides (84S697) gave 791, whereas reaction of 790 with isothiocyanates gave 792. 

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