Ketones, bromo substituted

CHEC-II(8)421>. Reaction of 94 with water can proceed by two different routes depending on the substitution pattern in the case of the bromo-substituted derivative the unsaturated ketone 97 was formed in high yield, whereas the derivative being unsubstituted at the pyrimidine moiety gave the methyl ester 98, also in very good yield. 

Silver(I) tetrafluoroborate converts a-bromo-substituted ketones, e.g. 7, to the corresponding fluoro-substituted ketones, e. g. 8, under anhydrous conditions.69 Attempts to convert the a-chloro-substituted ketenes under the same conditions failed.69... 

The direct bromination of aliphatic ketones occurs readily, often giving isomeric mixtures. Thus, methyl ethyl ketone and an equimolar quantity of bromine yield the a-btomomethyl (17%) and the a-bromoethyl (50%) isomers polybrominated products are also formed. On the other hand, only the tertiary hydrogen in methyl isopropyl ketone is substituted upon monobromination. By varying the conditions for the bromination of acetone, mono- or poly-substitution products may be formed e.g., bromo-acetone (44%), a,a -dibromoacetone (60%), and a,a,a -tribromoacetone (60%). ... 

Ketones monobrominated at the less substituted carbon are not readily prepared by simple bromination of unsymmetrical ketones, since substitution occurs mainly at the more substituted carbon. While the action of hydrobromic acid on diazoketones has long been the only method of preparing bromomethyl ketones, it has recently been shown that bromination of unsymmetrical ketals, e.g.. dioxolanes or dimethyl ketals) occurs to a greater extent on the less substituted carbon atom, and this constitutes an efficient route to the corresponding a-bromo ketones.Direct bromination of 2-substituted cyclohexanones and various methyl ketones in methanol leads to the same result. 

Another efficient method for the synthesis of polysubstituted pyrroles was described by Li et al. They found that CuI/iV,iV-dimethylglycine-catalyzed reaction of amines with y-bromo-substituted y,5-unsaturated ketone 126 underwent a condensation/coupling process to afford pyrroles 127 (Scheme 45) [82]. 

The high nucleophilicity of sulfur atoms is preserved, even if it is bound to electron withdrawing carbonyl groups. Thiocarboxylales, for example, substitute bromine, e.g. of a-bromo ketones. In the presence of bases the or-acylthio ketones deprotonate and rearrange to episulfides. After desulfurization with triphenylphosphine, 1,3-diketones are formed in good yield. Thiolactams react in the same way, and A. Eschenmoser (1970) has used this sequence in his vitamin B]2 synthesis (p. 261). 

While the use of substituted hydrazine derivatives is generally recognized to be the most reliable method for dehydrobromination of bromo ketones without rearrangement, this side reaction can be important in some cases. Both the 2-bromo-A" -3-ketone and its 4-bromo isomer give the same A" -diene hydrazone (33), °° which is cleaved to the ketone in very poor yield (however, see ref. 65 for a successful use of the semicarbazide method). 

The most selective 4-substitution is obtained in the Friedel-Crafts isopropylation of 2-acetylthiophene, which under certain conditions gives as much as 99% of this isomer and 1% of the 5-isomer. An--other case of selective 4-substitution is the bromination of 2-thienyl alkyl ketones using the swamping catalyst effect (i.e., brominating in the presence of excess AlCb without solvent), which yields 43-63% of apparently isomer-free 4-bromo-2-thienyl alkyl ketones. Gold-farb et al. also have applied this method to the chloromethylation of... 

Betzemeier et al. (1998) have used f-BuOOH, in the presence of a Pd(II) catalyst bearing perfluorinated ligands using a biphasic system of benzene and bromo perfluoro octane to convert a variety of olefins, such as styrene, p-substituted styrenes, vinyl naphthalene, 1-decene etc. to the corresponding ketone via a Wacker type process. Xia and Fell (1997) have used the Li salt of triphenylphosphine monosulphonic acid, which can be solubilized with methanol. A hydroformylation reaction is conducted and catalyst recovery is facilitated by removal of methanol when filtration or extraction with water can be practised. The aqueous solution can be evaporated and the solid salt can be dissolved in methanol and recycled. 

Alkyl- and aryl-hydrazones of aldehydes and ketones readily peroxidise in solution and rearrange to azo hydroperoxides [1], some of which are explosively unstable [2], Dry samples of the p-bromo- and p-fluoro-hydroperoxybenzylazobenzenes, prepared by oxygenation of benzene solutions of the phenylhydrazones, exploded while on filter paper in the dark, initiated by vibration of the table or tapping the paper. Samples were later stored moist with benzene at —60°C to prevent explosion [3], A series of a-phenylazo hydroperoxides derived from the phenyl-or p-bromophcnyl-hydrazones of acetone, acetophenone or cyclohexanone, and useful for epoxidation of alkenes, are all explosive [4], The stability of several substituted phenylazo hydroperoxides was found to be strongly controlled by novel substituent effects [5],... 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

Reduction of 2-bromo-3-pentanone at mercury affords a mixture of 3-pentanone and l-hydroxy-3-pentanone, whereas electrolysis of Q ,Q -dibromoacetone in the presence of benzoate gives a mixture of products arising from both a carbon-bromine bond cleavage and an Sn2 displacement of bromide by benzoate [94]. In an acetic acid-acetate buffer, branched dibromo ketones, such as 2,4-dibromo-2,4-dimethyl-3-pentanone, are reduced to a-acetoxy ketones however, less highly substituted compounds, such as 4,6-dibromo-5-nonanone, undergo simple cleavage of both carbon-bromine bonds [95]. Other work dealing with the reduction of Q, Q -dibromoketones has been described [96]. 

The retrosynthesis involves the following transformations i) isomerisation of the endocyclic doble bond to the exo position ii) substitution of the terminal methylene group by a more stable carbonyl group (retro-Wittig reaction) iii) nucleophilic retro-Michael addition iv) reductive allylic rearrangement v) dealkylation of tertiary alcohol vi) homolytic cleavage and functionalisation vii) dehydroiodination viii) conversion of ethynyl ketone to carboxylic acid derivative ix) homolytic cleavage and functionalisation x) 3-bromo-debutylation xi) conversion of vinyl trimethylstannane to methyl 2-oxocyclopentanecarboxylate (67). 

Bromoacetylthianthrene, which can be produced by direct acylation as well as via bromination of 2-acetylthianthrene (63MI2) (for comparable dibromination of 2,7-diacetylthianthrene, see 64MI1), has been used in its capacity as an a-bromo-ketone to produce thianthren-2-yl-substituted heterocycles such as 55, 56, 57 (63MI2 73BSF1460), and 2-amino-4-(thianthren-2-yl)thiazole (63MI2), by condensation with 2-aminopyridine,... 

---