Lead acetate methyl iodide

Historically, the rhodium catalyzed carbonylation of methanol to acetic acid required large quantities of methyl iodide co-catalyst (1) and the related hydrocarboxylation of olefins required the presence of an alkyl iodide or hydrogen iodide (2). Unfortunately, the alkyl halides pose several significant difficulties since they are highly toxic, lead to iodine contamination of the final product, are highly corrosive, and are expensive to purchase and handle. Attempts to eliminate alkyl halides or their precursors have proven futile to date (1). 

In a working catalytic system, however, the principal solvent component is acetic acid, so esterification (Eq. 2) leads to substantial conversion of the substrate into methyl acetate. Methyl acetate is activated by reaction with the iodide co-catalyst (Eq. 3) ... 

Methazolamide Methazolamide, N-(4-methyl-2-sulfamoyl-l,3,4-thiadiazol-5-yliden) acetamide (21.2.3), is made by an intermediate product of acetazolamide synthesis— 2-acetylamino-5-mercapto-l,3,4-thadiazol (9.7.3). This is benzylated with benzylchloride at the mercapto group, forming 2-acetylamino-5-benzylthio-l,3,4-thiadiazole (21.2.1). Further methylation of the product with methyl iodide leads to the formation of N-(4-methyl-2-benzylthio-l,3,4-thiadiazol-5-yliden)acetamide (21.2.2). Oxidation and simultaneous chlorination of the resulting product with chlorine in an aqueous solution of acetic acid, and reacting the resulting chlorosulfonic derivative with ammonia gives (21.2.3) [5-7]. 

Acetyl iodide is very reactive and it reacts efficiently with water or methanol leading to acetate compounds. Hydrolysis of acetyl iodide along with the subsequent conversion of methanol to methyl iodide are very rapid under the reaction conditions leading to a complete mechanistic cycle. 

The iodide content of the catalyst formulation is the key to avoiding these problems of competing reactions and achieving maximum acetic acid selectivity. The addition of iodide ensures that any initially formed methanol (7) is rapidly (H) converted to the more electrophilic methyl iodide. However, further increases in the quantities of iodide beyond that needed for methanol conversion to methyl iodide may lead to a portion, or all, of the catalytic-ally active cobalt carbonyl reverting to catalytically inactive cobalt iodide species - e.g. the [Col4] anion identified in this work, or possibly the cationic [Co(MeOH) (CO) I species (9). 

The hydroxyquinoline (39-2) provides the starting material for a quinolone that incorporates a hydrazine function. Reaction of (39-2) with 2,4-dintrophenyl O-hydroxylamine ether (41-1) in the presence of potassium carbonate leads to a scission of the weak N-O hydroxylamine bond by the transient anion from the quinolone the excellent leaving character of 2,4-dinitrophenoxide adds the driving force for the overall reaction, resulting in alkylation on nitrogen to form the hydrazine (41-2). The primary amine is then converted to the formamide (41-3) by reaction with the mixed acetic-formic anhydride. Alkylation of that intermediate with methyl iodide followed by removal of the formamide affords the monomethylated derivative (41-4). Chlorine at the 7 position is then displaced by A-methylpiperazine and the product saponified. There is thus obtained amifloxacin (41-6) [48]. 

The remaining four hydroxyl groups can be methylated in basic solution by dimethyl sulfate or by methyl iodide and silver oxide in N,N-dimethyl-methanamide, HCON(CH3)2, solution. Hydrolysis of either of these penta-methyl glucose derivatives with aqueous acid affects only the acetal linkage and leads to a tetramethylated glucose, 20, as shown in Figure 20-4. 

While the addition-oxidation and the addition-protonation procedures are successful with ester enol-ates as well as more reactive carbon nucleophiles, the addition-acylation procedure requires more reactive anions and the addition of a polar aptotic solvent (HMPA has been used) to disfavor reversal of anion addition. Under these conditions, cyano-stabilized anions and ester enolates fail (simple alkylation of the carbanion) but cyanohydrin acetal anions are successful. The addition of the cyanohydrin acetal anion (71) to [(l,4-dimethoxynaphthalene)Cr(CO)3] occurs by kinetic control at C-P in THF-HMPA and leads to the a,p-diacetyl derivative (72) after methyl iodide addition, and hydrolysis of the cyanohydrin acetal (equation 50).84,124-126... 

Most recently, our total synthesis was streamlined further. Since the Claisen rearrangement which provided 32 required excess base, and was followed in a separate step by dianion formation, it seemed reasonable that the two steps could be combined. For example, treatment of acetate 30 with several equivalents of base should lead directly to the dianion of 32, which could then be alkylated in situ to provide the homologated acid 41. Indeed, treatment of 30 with four equivalents of LDEA (-78 to 50 °C) provided the desired dianion of 32, which upon cooling and admission of methyl iodide, gave the acid 41 in 57% yield. 

Scheme 6 describes the most important reactions of the perimidinespirocyclo-hexadienone 1. A treatment of 1 (R = H) in dimethylsulfoxide (DMSO) solution with methyl iodide in the presence of potassium carbonate affords the A-m ethyl derivative la (R = Me), whereas use of an excessive amount of methyl iodide in this reaction leads to the A,A -dimethyl derivative of the ring-closed tautomer.4,7 By contrast, acylation of la by acetic anhydride or its tosylation by treatment with p-toluenesulfonyl chloride results in the formation of the respective derivatives of the ring-opened tautomeric form lb. 

The dimethyl amine derivative produced was quaternized directly by methyl iodide, added slowly to a chilled solution of the ternary amine in ethyl acetate. When other ring substituents are present, the reductive eunination leads to isomeric configurations, as noted in Table I. Quaternary ammonium halide salts were characterized by melting point, TLC, or microanalytical data and and NMR. 

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