Haloform catalysts

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

Lai96-99 has reported a general method of preparation of substituted piperazinones (54) via reactions of ketones and haloform in the presence of quaternary ammonium catalysts. 

Fluorinated alkenes are able to insert into weak C-H bonds of various compounds branched alkanes, haloforms. alcohols, ethers, aldehydes and their corresponding ketals. These reactions usually involve the use of UV irradiation or radical-initiation catalysts, such as peroxides or azobisisonitriles. Variable amounts of telomcric products are also formed. Under the influence of ) -irradiation ( °Co source), one-to-one adducts are obtained predominantly. Attack of the intermediate radical occurs preferentially on the less-hindered carbon of the fluorinated alkene. 

A value of kH/kD = 1.4 was obtained [114] for the rate of proton transfer compared with deuteron transfer from chloroform to hydroxide ion and this result is similar to the values determined earlier for several haloforms [164, 166]. In the most recent work [171(b)] a value kH /kD = 1.11 0.05 was determined for chloroform. These values are close to those observed for reaction of cyanocarbon acids (though a different base catalyst is involved) and in Sect. 4.3 it was argued that isotope effects as low as these are expected for a transition state in which proton transfer is almost complete. The isotope effect for proton transfer from chloroform was measured using a new and useful method [114]. It can be shown that the ratio of initial rates of uptake of tritium for the first ten per cent of reaction from tritiated water into CHC13 and CDC13 is identical to the primary isotope effect for proton loss (feH /fcD). The procedure can be used for measuring isotope effects on proton transfer from carbon acids to hydroxide ion or buffer catalysts and is more convenient than other methods. Other methods which have been used, for example, involve the comparison of rates of detritiation and dedeuteration or the comparison of rates of bromination for isotopically different acids (RCH and RCD) [113]. 

Besides the synthesis of 1-chloroalkyl carbonates, this method is general enough to be used for the preparation of 1-fluoroalkyl, 1-bromoalkyl or 1-iodoalkylcarbonates as shown in table 3-7. However, the method gives poor results or even failed when the haloformate is too unstable in presence of the catalyst (see section 3-2-1). For example, attempts to prepare 1-chloroethyl ethyl carbonate (CEEC) itself in 1,2 dichloroethane at 60°C with 0.05 equ. pyridine, gave almost total decomposition of ethyl chloro-formate. 

Depending on the catalyst system and the chosen reaction conditions, aliphatic and aromatic alcohols can in general act as substrates for oxidative carbonylations. In principle this reaction type can occur in the presence of metal ions which are able to oxidize CO in the presence of an alcohol function. As already mentioned above, it is also here necessary to carry out the reaction in the presence of a suitable reoxidant in order to establish a catalytic cycle process. Preferably that may be another metal salt, for example CuCU- Typical products and side products which are observed in the oxidative carbonylation of alcohols are alkyl and aryl carbonates, oxalates, formates, haloformates, acetals, and carbon dioxide. 

Bartlett, P. D. Enolization as directed by acid and basic catalysts. II. Enolic mechanism of the haloform reaction. J. Am. Chem. Soc. 1934,... 

Color reactions Boric acid (hydroxyquinones). Dimethylaminobenzaldehyde (pyrroles). Ferric chloride (enols, phenols). Haloform test. Phenylhydrazine (Porter-Silber reaction). Sulfoacetic acid (Liebermann-Burchard test). Tetranitromethane (unsaturation). Condensation catalysts /3-Alanine. Ammonium acetate (formate). Ammonium nitrate. Benzyltrimethylammonium chloride. Boric acid. Boron trilluoride. Calcium hydride. Cesium fluoride. Glycine. Ion-exchange resins. Lead oxide. Lithium amide. Mercuric cyanide. 3-Methyl-l-ethyl-2-phosphoiene-l-oxlde. 3-Methyl-1-phenyi-3-phoipholene-1-oxide. Oxalic acid. Perchloric acid. Piperidine. Potaiaium r-butoxIde. Potassium fluoride. Potassium... 

A reaction of haloforms with a base, which generates dihalocarbenes (a-elimination) and their addition to alkenes is an efficient method for the preparation of 1,1-dihalocyclopropanes, with the exception of 1,1-difluoro derivatives (Houben-Weyl, Vol.E19b, pp 1464-1466). When chlorodifluoromethane and an alkene are treated with methyllithium, potassium tcrt-butox-ide, powdered sodium hydroxide in tetraglyme or a concentrated aqueous solution of alkali metal hydroxide and a phase-transfer catalyst, the expected 1,1-difluorocyclopropanes are formed in low yields. Comparable low yields of these products result, if dichlorodi-fluoromethane and an alkene are treated with methyllithium. " The main products formed are those that result from reaction of difluorocarbene (carbenoid), and its precursor, with the base or the solvent present in the system (for examples, see refs 10-12). Therefore, the reaction of chlorodifluoromethane with base and an alkene lacks preparative value. The difficulties mentioned above are circumvented in the method using chlorodifluoromethane, oxirane (or chloromethyloxirane), with tetraalkylammonium halide as a catalyst and an alkene (Houben-eyl, Vol. 4/3, p 380 and Vol. E19b, pp 1468-1469). 

Elimination Reactions. t-BuOK is a widely used base for both a- and /3-elimination reactions. It is the most effective base in the conventional alkoxide-haloform reaction for the generation of dihalocarbenes. This procedure still finds general use (eq 19), but since it requires anhydrous conditions, it has been replaced to a degree by use of phase-transfer catalysts. Vinylidene carbenes have also been produced from the reaction of a-halo allenes with f-BuOK. ... 

Haloform reactions are generally performed with halogens in the presence of hydroxide [251] or directly with hypohalites [252]. Alternative methods affording carboxylic acids from methyl ketones (or other enolizable substrates) include the aerobic oxidation in the presence of a catalytic amount of dinitrobenzene [253] with a base in a dipolar aprotic solvent such as DMF [254] or HMPT (hexamethylphospho-ric triamide) [255, 256] and the use of stoichiometric quantities of hypervalent iodide derivatives [95, 257] or nitrosylpentacyanoferrate [258]. Furthermore, metal catalysts can be used, and systems such as tert-butyl hydroperoxide in the presence of rhenium oxide [259], oxygen in combination with a copper complex [260], heteropolyacids [261] and Mn"/Co" systems [262] were found to be applicable. Finally, aryl ketones are selectively oxidized to aliphatic carboxylic acids by treatment with periodate [81] in the presence of ruthenium trichloride [263]. 

Now let s draw the forward scheme. The starting alcohol is oxidized upon treatment with chromic acid (alternatively, PCC can be used for this step). The resulting ketone is then treated with molecular bromine (Br2) and sodium hydroxide, followed by aqueous acid, to give a carboxylic acid (via a haloform reaction). Finally, the carboxylic acid is treated with ethanol in the presence of an acid catalyst, giving the desired ester (via a Fischer esterification). 

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