Alkylation with dialkyl carbonates

Excess dialkyl carbonate can be the solvent. No by-product salts are formed. The by-product alcohol and carbon dioxide could be recycled. Aiylacetonitriles, phenols, aromatic amines, trialkylamines, acetylenes, silica, and titania can also be alkylated with dialkyl carbonates. 

CycHc carbonates are made by treating 1,2-diols with dialkyl carbonates using an alkyl ammonium and tertiary amine catalyst. The combination of propylene glycol and dimethyl carbonate has been reported to result in a 98% yield of propylene carbonate (21). 

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>. 

Acylation of alkylnitriles is best accomplished by low-temperature reaction with dialkyl carbonates or alkyl chloroformates [C1C(0)0R] in the presence of excess... 

Among other reactions, the bis-metallated species (151) derived from nitroalkanes condense with dialkyl carbonates to give comp>ounds (152), in 60—80% yield, which can serve as precursors of both a-amino-acids and a-hydroxyamino-esters as well as a-keto-esters. Oxazolin-5-ones (153) can be alkylated at the 4-position by alkyl halides in hot DMF containing HMPA and ethyldi-isopropylamine. Yields are good (60—90%) for allylic, benzylic, and propargylic halides but otherwise poor (e.g. 32% with EtI) under these conditions acid hydrolysis of the products affords substituted a-amino-acids. Mesoionic l,3-oxazol-5-ones (154), obtained from imidoyl chlorides and acyl-tetracarbonylferrates, react with alcohols to give N-acyl-a-amino-acid esters. ... 

Ketones, in which one alkyl group R is sterically demanding, only give the trans-enolate on deprotonation with LDA at —12°C (W.A. Kleschick, 1977, see p. 60f.). Ketones also enolize regioseiectively towards the less substituted carbon, and stereoselectively to the trans-enolate, if the enolates are formed by a bulky base and trapped with dialkyl boron triflates, R2BOSO2CF3, at low temperatures (D A. Evans, 1979). Both types of trans-enolates can be applied in stereoselective aldol reactions (see p. 60f.). 

One of the advantages of the enamine alkylation reaction over direct alkylation of the ketone under the influenee of strong base is that the major product is the monoalkylated derivative 29,32). When dialkylation is observed, it occurs at the least substituted carbon in contrast to alkylation with base, where the a-disubstituted product is formed. Dialkylation becomes the predominant reaction when a strong organic base is added and an excess of alkyl halide is used (29). Thus 1-N-pyrrolidino-l-cyclo-hexene (28) on treatment with two moles of allyl bromide in the presence of ethyl dicyclohexylamine (a strong organic base which is not alkylated under the reaction conditions) gave a 95 % yield of 2,6-diallylcyclohexanone (29). 

A carboxylic acid (not the salt) can be the nucleophile if F is present. Mesylates are readily displaced, for example, by benzoic acid/CsF. Dihalides have been converted to diesters by this method. A COOH group can be conveniently protected by reaction of its ion with a phenacyl bromide (ArCOCH2Br). The resulting ester is easily cleaved when desired with zinc and acetic acid. Dialkyl carbonates can be prepared without phosgene (see 10-21) by phase-transfer catalyzed treatment of primary alkyl halides with dry KHCO3 and K2C03- ... 

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

Ito and co-workers observed the formation of zinc bound alkyl carbonates on reaction of carbon dioxide with tetraaza macrocycle zinc complexes in alcohol solvents.456 This reversible reaction was studied by NMR and IR, and proceeds by initial attack of a metal-bound alkoxide species. The metal-bound alkyl carbonate species can be converted into dialkyl carbonate. Spectroscopic studies suggested that some complexes showed monodentate alkyl carbonates, and varying the macrocycle gave a bidentate or bridging carbonate. Darensbourg isolated arylcarbonate compounds from zinc alkoxides as a by-product from work on polycarbonate formation catalysis.343... 

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]. 

The replacement of both -OH groups with chlorine produces Ccirbonyl dichloride, also known as phosgene, a useful reactant. For example, phosgene reacts with two moles of alcohol to form a dialkyl carbonate. The reaction of phosgene with one mole of alcohol produces an alkyl chloroformate, which is a useful intermediate in organic syntheses. The reaction of phosgene with four moles of ammonia yields urea and two moles of ammonium chloride, NH Cl. Figure 12-40 shows the structures of some of these compounds. 

Reaction with alcohol can produce two different types of products. While two molar equivalent of alcohol yields dialkyl carbonate, with one molar equivalent of alcohol the product is an alkyl chloroformate ... 

The reaction of aliphatic and aromatic ketone oximes 97 with a dialkyl carbonate 98 in the presence of K2CO3 at 180-190 °C yields 3-alkyl-4,5-disubstituted-2(3//)-oxazolones 104 in 22-48% yields. Mechanistically, it is proposed that N-alkylation of the initially formed oxime O-carbonate 99 yields 100, which affords the enamine 101 in the presence of base. A [3,3] sigmatropic rearrangement ensues to produce 102, which then cyclizes to 104. In cases where 97 contains two methylene groups in proximity to the C=N bond, one of which is benzylic, the above reaction sequence is regioselective for the benzylic methylene group (Fig. 5.25 Table 5.6, Fig. 5.26). ... 

An intermediate aziridinium ion accounts for the observation that alkylations with /S-haloalkyl tertiary amines frequently lead to products with a rearranged carbon-nitrogen skeleton. For example. l-dialkyl-arruno2-jsubstitufc d propanes may form 2-dialkylamino-l-subBtituted... 

The alkylation reaction of various alkali and alkaline-earth metal carbonates with alkyl halides R(CH2)nX (X = Cl, Br, I) is a primary synthetic procedure in organic chemistry for obtaining various symmetrical and unsymmetrical dialkyl carbonates under phase-transfer conditions in polar aprotic solvents [45]. Excellent yields may be obtained by running the reaction at 383 K in ionic liquids such as... 

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). 

Because of the large excess of ethylene present in the growth reactor, the reverse reaction is insignificant. Ethylene reacts with dialkyl aluminum hydride much more rapidly than does the terminal olefin, and any alkyl group thermally displaced is replaced by an ethyl group. However, terminal olefin present in the growth reactor can react with trialkylaluminum compounds. The a-olefin inserts between the aluminum-carbon bond just as ethylene does in a normal growth process. 

The standard preparation of 2-oxazolidinones is by treatment of /3-amino alcohols with phosgene or its synthetic equivalents ethyl chloroformate, dialkyl carbonates or even urea (equation 174). Isocyanates react with oxiranes in the presence of amines to yield 2-oxazolidinones (equation 175) (79LA200). The action of isocyanates on cyclic carbonates results in 2-oxazolidinones (equation 176) and photolysis of alkyl azidoformates affords oxazolidinones via intermediate nitrenes (equation 177). 

Brominations are performed by dropping solutions containing the stoichiometrically required amount of bromine to the stirred solutions of the diorgano tellurium compounds. To prevent tellurium-carbon bond cleavage, which may occur with dialkyl and alkyl aryl tellurium compounds, the reactions should be performed at or below 20°. The likelihood of Te —C bond cleavage decreases from chlorine to iodine. 

Thiazolidinedione (2) is readily alkylated at the 3-position when treated with alkyl chlorides for 5 minutes at 142°-145° in DMF with potassium carbonate (Scheme 2).101 Prolonged reaction at temperatures above 120° resulted in decreased yields of 82 and in formation of 1,3-dialkylated ureas via ring degradation.101 Treatment of the potassium salt of 2 (83) with primary alkyl halides102 has been demonstrated to be the most versatile alkylation procedure, by which a wide range of functionalized side chains have been appended to the 3-position.103-106 3-Methylthiazolidine-dione (82 R = Me) is conveniently prepared from 2 by treatment with... 

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