Potassium dialkylation, alkylation

The 0,5-dialkyl dithiocarbonates (Table 4.8) are readily prepared under phase-transfer catalytic conditions by the reaction of an alkylating agent with potassium O-alkyl dithiocarbonate [35, 39], which can be obtained from carbon disulphide and the appropriate potassium alkoxide [cf. 40]. Monosaccharides are converted into 5-glycosyl dithiocarbonates via the in situ formation of the tosylate, followed by reaction with potassium O-alkyl dithiocarbonate (Scheme 4.6) [41], In a similar manner, 5-glycosyl 7V,7V-diethyldithiocarbamates are obtained from the monosaccharide and A.A-diethyldithiocarbamate (see 4.3.2) [42]. 

The alkylating agent (50 mmol) is added to a stirred solution of potassium O-alkyl dithio-carbonate (50 mmol) and Aliquat (1.68 g, 4 mmol) in H20 (50 ml). The mixture is stirred until the aqueous phase is completely colourless (Table 4.8) and petroleum ether (b.p. 40-60 °C, 150 ml) is then added. The organic layer is separated, dried (MgS04), filtered through silica, and evaporated under reduced pressure to yield the 0,5-dialkyl ester. 

In a one-pot synthesis of thioethers, starting from potassium 0-alkyl dithiocarbonate [36], the base hydrolyses of the intermediate dialkyl ester, and subsequent nucleophilic substitution reaction by the released thiolate anion upon the unhydrolysed 0,5-dialkyl ester produces the symmetrical thioether. Yields from the O-methyl ester tend to be poor, but are improved if cyclohexane is used as the solvent in the hydrolysis step (Table 4.13). In the alternative route from the 5,5-dialkyl dithiocarbonates, hydrolysis of the ester in the presence of an alkylating agent leads to the unsymmetrical thioether [39] (Table 4.14). The slow release of the thiolate anions in both reactions makes the procedure socially more acceptable and obviates losses by oxidation. 

Oxidation of Sulfoxides. Dialkyl, alkyl aryl, and diaryl sulfoxides are readily oxidized to sulfones in excellent yields under mild conditions (—30 °C) in MeCN by the peroxy intermediate (1). Oxidation of the unsaturated sulfoxide (11) was chemose-lective it furnished the sulfone (12) in 70% yield when reacted with (1) for 5 h. The double bond was not epoxidized. Similar chemoselective epoxidation has been carried out with only one other reagent (potassium hydrogen persulfate). ... 

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

Primary and secondary alkyl haUdes and sulfonates react with potassium superoxide to form dialkyl peroxides (101,102) (eq. 28). Dia2oalkanes, eg, dia2omethane, have been used to alkylate hydroperoxides (66) (eq. 29). 

It is noteworthy that only in the case of dehydroquinolizidine derivatives does monomethylation produce the N-alkylated product. The formation of dialkylated products can be explained by a disproportionation reaction of the monoalkylated immonium salt caused by either the basicity of the starting enamine or some base added to the reaction mixture (most often potassium carbonate) and subsequent alkylation of the monoalkylated enamine. Reinecke and Kray 113) try to explain the different behavior of zJ -dehydroquinolizidine and zJ -dehydroquinolizidine derivatives by the difference in energies of N- and C-alkylation transition states because of the presence of I strain. 

The phase-transfer catalysed reaction of alkyl halides with potassium carbonate in dimethylacetamide, or a potassium carbonate/potassium hydrogen carbonate mixture in toluene, provides an excellent route to dialkyl carbonates without recourse to the use of phosgene [55, 56], An analogous reaction of acid chlorides with sodium hydrogen carbonate in benzene, or acetonitrile, produces anhydrides (3.3.29.B, >80%), although there is a tendency in acetonitrile for aliphatic acid chlorides to hydrolyse yielding the acids [57]. 

An alternative route to sulphones utilizes the reaction of the appropriate activated halide with sodium dithionite or sodium hydroxymethanesulphinite [6], This procedure is limited to the preparation of symmetrical dialkyl sulphones and, although as a one-step reaction from the alkyl halide it is superior to the two-step oxidative route from the dialkyl sulphides, the overall yields tend to be moderately low (the best yield of 62% for dibenzyl sulphoxide using sodium dithionite is obtained after 20 hours at 120°C). The mechanism proposed for the reaction of sodium hydroxymethanesulphinite is shown in Scheme 4.20. The reaction is promoted by the addition of base and the best yield is obtained using Aliquat in the presence of potassium carbonate. It is noteworthy, however, that a comparable yield can be obtained in the absence of the catalyst. The reaction of phenacyl halides with sodium hydroxy-methane sulphinite leads to reductive dehalogenation [7]. 

Mono-A-alkylation of the amides occurs under relatively mild liquiddiquid two-phase conditions (Table 5.10), using concentrated aqueous sodium or potassium hydroxide. Under soliddiquid conditions with sodium hydroxide-potassium carbonate or potassium hydroxide, or by using super-saturated aqueous potassium or sodium hydroxide, it is possible to control the reaction to obtain either the mono-or dialkylated derivatives f2-4]. Soliddiquid two-phase conditions also provide the most effective route to mono-AI-alkylalion of weakly acidic aliphatic amides, but it has been suggested that the procedure is not sufficiently selective for the monoalkylation of the more acidic amides [4],... 

Mildly basic liquiddiquid conditions with a stoichiometric amount of catalyst prevent hydrolysis during alkylation [101] and, more recently, it has been established that solid-liquid or microwave promoted reactions of dry materials are more effective for monoalkylation [102-106] of the esters and also permits dialkylation without hydrolysis. Soliddiquid phase-transfer catalytic conditions using potassium f-butoxide have been used successfully for the C-alkylation of diethyl acetamido-malonate and provides a convenient route to a-amino acids [105, 107] use of potassium hydroxide results in the trans-esterification of the malonate, resulting from hydrolysis followed by O-alkylation. The rate of C-alkylation of malonic esters under soliddiquid phase-transfer catalytic conditions may be enhanced by the addition of 18-crown-6 to the system. The overall rate is greater than the sum of the individual rates observed for the ammonium salt or the crown ether [108]. 

Persson et al. (1991) used diffuse reflection infrared Fourier transform (DRIFT) spectroscopy to study the interactions between galena, pyrite sphalerite and ethyl xanthate. They provided the evidence that the DRIFT spectrum of oxidized galena treated with an aqueous solution of potassium ethyl xanthate is practically identical with that of solid lead (II) ethyl xanthate, which can be formed as the only detectable siuface species on oxidized galena. Dialkyl dixanthogen is formed as the only siuface species in the reaction between oxidized pyrite and aqueous solution of potassium alkyl xanthate. 

The 3-phenylpyrimido[5,4-( ]-l,2,4-triazines 29 (also known as 3-phenylreumycins where R = Me) can be transformed into the corresponding 1,6-disubstituted analogues 30 upon selective alkylation with dialkyl sulfates or alkyl halides in DME in the presence of potassium carbonate as shown in Equation (2) <2001J(P1)130, 1997H(45)643>. 

Alkylation of the exocyclic amino group of the 4-amino-6-phenylpyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxide 95, shown in Equation (14), with ethyl iodide and potassium carbonate in acetone gave the corresponding 4-ethyl-amino derivative 96 in a clean and efficient manner, although the researchers noted that the procedure is not general due to competitive formation of dialkylated products <2000JME4219>. The procedure described in Section 10.20.6.3 (Equations 10 and 11) is, in fact, a more efficient entry to 4-alkylamino pyrazino[2,3-c] [ 1,2,6]thiadiazine 2,2-dioxide. 

The diselenides, RSe.SeR, are prepared by the interaction of potassium diselenide and dialkyl sulphates or alkyl halides ... 

The preparation of diallyl cyanamide by the above method has only recently been described in the literature.1 However, other dialkyl cyanamides have been prepared by the following methods the action of chlorocyanogen or bromocyanogen on dialkyl amines 2 the reaction of dialkylchloroamines with potassium cyanide 3 the action of bromine on a mixture of dialkyl amines and potassium cyanide 4 the action of alkyl halides on disilver cyanamide5 and on disodium cyanamide.6 Dimethyl cyanamide has also been prepared by the action of dimethyl sulfate on lime nitrogen 7 and on cyanamide. 8... 

N(l)-Alkylation of 1,6,7,8,9,9a-hexahydro-4-oxo-4//-pyrido[l,2-a]py-rimidine-3-carboxamide 368 was carried out with dialkyl sulfate in water in the presence of sodium hydroxide, with triethyl phosphate in the presence of potassium carbonate at 235°C, and with butyl bromide in boiling ethanol in the presence of potassium carbonate for 30 hours (83SZP635101 85JOC2918). 

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