Methyl halides carbonylation

Reaction rates have first-order dependence on both metal and iodide concentrations. The rates increase linearly with increased iodide concentrations up to approximately an I/Pd ratio of 6 where they slope off. The reaction rate is also fractionally dependent on CO and hydrogen partial pressures. The oxidative addition of the alkyl iodide to the reduced metal complex is still likely to be the rate determining step (equation 8). Oxidative addition was also indicated as rate determining by studies of the similar reactions, methyl acetate carbonylation (13) and methanol carbonylation (14). The greater ease of oxidative addition for iodides contributes to the preference of their use rather than other halides. Also, a ratio of phosphorous promoter to palladium of 10 1 was found to provide maximal rates. No doubt, a complex equilibrium occurs with formation of the appropriate catalytic complex with possible coordination of phosphine, CO, iodide, and hydrogen. Such a pre-equilibrium would explain fractional rate dependencies. 

The preparation of acetic acid represents a special case. Olah and coworkers as well as Hogeveen and coworkers have demonstrated that CO can react with methane under superacidic conditions, giving the acetyl cation and by subsequent quenching acetic acid or its derivatives (see Section 7.2.3). Monosubstituted methanes, such as methyl alcohol (or dimethyl ether), can be carbonylated to acetic acid.115 Similarly, methyl halides undergo acid-catalyzed carbonylation.115,116 Whereas the acid-catalyzed reactions can be considered as analogs of the Koch reaction, an efficient Rh-catalyzed carbonylation of methyl alcohol in the presence of iodine (thus in situ forming methyl iodide) was developed by Monsanto and became the dominant industrial process (see Section 7.2.4). 

Finally, it should be mentioned that there is one important commercial application of the organic halide carbonylation. This is in the rhodium and methyl iodide-catalyzed conversion of methanol and carbon monoxide into acetic acid (25). The mechanism of the reaction appears to involve the oxidative addition of methyl iodide to the rhodium(I) catalyst followed by CO insertion and hydrolysis ... 

Reactions of the Enolate of (1) with Electrophiles. Addition of the dioxolanones (1) to solutions of Lithium Diiso-propylamide or Lithium Hexamethyldisilazide in THF at dry-ice temperature generates the corresponding enolates which react with alkyl halides, - carbonyl compounds, and nitroalkenes almost exclusively from the face remote from the t-Bu group to give products of type (2). These can be hydrolyzed to simple ot-hydroxy-ot-methyl carboxylic acids or further elaborated. Four examples are shown in (3)-(6) in which the part of the molecule originating from lactic acid is indicated in bold. 

The key elements of these carbonylation processes is the ability of a metal complex to undergo facile oxidative addition with methyl halide (especially iodide), carbon monoxide (CO) insertion into the methyl-metal bond, and reductive elimination of the acetyl group as the acetyl halide [3]. 

Stabilized telluronium ylides such as dibutyltelluronium carbethoxy, phenacyl/ cyano- and carbamoylmethylide (easily prepared by the reaction of dibutyl tellurides with the appropriate substituted methyl halides, followed by treatment with a base), undergo Wittig-type olefmation reactions with a variety of carbonyl compounds, giving the expected olefins in satisfactory yields (method A). This behaviour is in sharp contrast to that of stabilized sulphonium yhdes, which are inert towards carbonyl compounds. 

Alkylation of the a-carbon of a carbonyl compound is an important reaction because it gives us another way to form a carbon-carbon bond. Alkylation is carried out by first removing a proton from the a-carbon with a strong base such as LDA and then adding the appropriate alkyl halide. Because the alkylation is an Sn2 reaction, it works best with methyl halides and primary alkyl halides (Section 10.2). 

Methyl ketones, aldols, 1,4-diketones. Japanese chemists have used this allyl dithiocarbamate for introduction of the CH3COCH2 group into various electrophiles alkyl halides, carbonyl compounds, and epoxides. Typical results are summarized in equations I-III. The reagent is first converted into the lithium salt (2) by LDA in THF at -78° in essentially quantitative yield. 

The direct replacement of chlorine in 2-chlorotetrahydrothiophene by means of MeSH leads to low yields of (339). However, reaction with diphenylacetic acid and EtjN gives the diphenylacetic ester which can be converted to (339) in excellent yield by MeSH. Alternatively, 2-mercaptotetra-hydrothiophene can be prepared by the thiourea method (CHEC-I) and methylated to give (339) <92CB1641>. Deprotonation of (339) with Bu"Li at —30°C gives the 2-lithio derivative this reacts with a variety of electrophiles (alkyl halides, carbonyl compounds) to form (340) (Scheme 69). 

Imido and oxo species react with a variety of electrophiles that include protons, alkyl halides, carbonyl compounds, and heterocumulenes. Representative reactions of oxo and imido complexes with acid and methyl bromide are shown in Equations 13.85-13.89. 

Carbonylation and decarbonylation reactions of alkyl complexes in catalytic cycles have been reviewed . A full account of the carbonylation and homologation of formic and other carboxylic acid esters catalysed by Ru/CO/I systems at 200 C and 150-200 atm CO/H2 has appeared. In a novel reaction, cyclobutanones are converted to disiloxycyclopentenes with hydrosilane and CO in the presence of cobalt carbonyl (reaction 4) . The oxidative addition of Mel to [Rh(CO)2l2] in aprotic solvents (MeOH, CHCI3, THF, MeOAc), the rate determining step in carbonylation of methyl acetate and methyl halides, is promoted by iodides, such as Bu jN+I", and bases (eg 1-methylimidazole) . A further kinetic study of rhodium catalysed methanol carbonylation has appeared . The carbonylation of methanol by catalysts prepared by deposition of Rh complexes on silica alumina or zeolites is comparable with the homogeneous analogue . 

McNeill 11,12) has established that the initial step when a transition metal halide is combined with PMMA is coordination of the metal ion to the carbonyl oxygens of the polymer. This is usually followed by the loss of methyl halide and the formation of a metal polymethacrylate. TGA/IR has provided interesting means to probe these systems to compare results using manganese chloride IS) and chromium (111) diloride 19) as PMMA additives. Weight loss data and identification of the evolved gases for both additives are rqwrted below in Table 1. 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

The unstable CH TiCl [12747-38-8] from (CH3 )2 2n + TiCl forms stable complexes with such donors as (CH2)2NCH2CH2N(CH2)2, THF, and sparteine, which methylate carbonyl groups stereoselectively. They give 80% of the isomer shown and 20% of the diastereomer this is considerably more selective than the mote active CH MgBt (201). Such complexes or CH2Ti(OC2H2 methylate tertiary halides or ethers (202) as follows ... 

Cyclic g-haloacetals and -ketals have been prepared by variations on two basic methods. The most frequently used method involves the combination of an a,B-unsaturated carbonyl compound (acrolein, methyl vinyl ketone, croton-aldehyde, etc.) a diol, and the anhydrous hydrogen halide. All possible sequences of combining these three have been used. In most cases the... 

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