Monoalkyl 2- acetate

Commercial dialkyl-anilines may be purified by refluxing with an excess of acetic anhydride any unchanged aniline and monoalkyl-aniline are converted into the difficultly-volatile acetyl derivatives ... 

Monoalkylated and dialkylated acetic acids can be prepared by the malonic ester synthesis, but trialkylated acetic acids (R3CCO2H) can t be prepared. Explain. 

Aminotrimethanephosphonic acid is formed from formamide, acetamide, urea, or alkanenitriles with phosphorous acid [296]. By reaction of monoalkyl phosphite or P406 with glacial acetic acid or the corresponding anhydride ethane-1 -hydroxy-1,1-diphosphonic acid is formed after hydrolysis [297,298]. P406 can be obtained from P4 and 02 in a high yield of 85-90% [299]. 

Aldoximes can be oxidatively dehydrogenated to nitrile oxides using a variety of oxidants such as lead tetraacetate [16a], alkali hypohalites [lla],NBS in DMF followed by base treatment [16b], chloramine-T [11b], 1-chlorobenzotriazole [16c], mercuric acetate [ 16 d], etc. However, we employed either NaOCl or chloramine-T for most of our INOC reactions. For instance, a piperidine ring fused to an isoxazoline as in 14 was constructed using the INOC methodology (Scheme 3) [17]. Monoalkylation of N-tosylallylamine 10 with the bromoacetal... 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Several monoalkylations of functionalized acetates (Eq. 35) have been described in a series of papers the reactions were performed on potassium carbonate, either pure or mixed with potassium hydroxide. Some significant results are given in Tab. 5.13. 

Monoalkylation of a vic-glycol.1 Selective monoalkylation or monoacylation of the vic-glycol group of dimethyl L-tartrate is possible by conversion to the O-stannylene acetal (1) by reaction with dibutyltin oxide. The acetal is converted selectively to a mono derivative (3) by reaction with an alkyl halide or acyl chloride (excess) and CsF (about 2 equiv.). KF or Bu4NF are less effective than CsF. 

Phosphoric Acid and its Derivatives.—Triacetyl phosphate18 and diammonium monoacetyl phosphate14 have been obtained by acetylation of phosphoric acid with keten at —10 to —15 °C in diethyl ether and ethyl acetate, respectively the reaction can be controlled to give 90% yields of either product. Long-chain monoalkyl... 

Selective monoalkylation of methyl aryl-acetates by alkylhalides is difficult with conventional bases. It may be achieved by application of the three-step procedure outlined above adding (33) to the methyl arylacetates at a low temperature... 

Monoalkyl ethers of (R,R) 1,2-bis[3,5-bis(trifluoromethyl)phenyl]ethanediol, 24, have been examined for the enantioselective protonation of silyl enol ethers and ketene disilyl acetals in the presence of SnCU (Scheme 12.21) [25]. The corresponding ketones and carboxylic acids have been isolated in quantitative yield. High enantioselectivities have been observed for the protonation of trimethylsilyl enol ethers derived from aromatic ketones and ketene bis(trimethylsilyl)acetals derived from 2-arylalkanoic acids. 

Monoalkylation of a-isocyano esters by using tert-butyl isocyano acetate (R = fBu) has been reported by Schollkopf [28, 33]. Besides successful examples using primary halides, 2-iodopropane has been reported to produce the a-alkylated product (1) as well by this method (KOfBu in THF). In the years 1987-1991, Ito reported several methods for the monoalkylation of isocyano esters, including the Michael reaction under TBAF catalysis as described earlier [31], Claisen rearrangements [34], and asymmetric Pd-catalyzed allylation [35]. Finally, Zhu recently reported the first example of the introduction of an aromatic substituent by means of a nucleophilic aromatic substitution (Cs0H-H20, MeCN, 0°C) in the synthesis of methyl ot-isocyano p-nitrophenylacetate [36]. 

The benzylic alcohol 6-bromo-9-ethylcarbazole-3-ylcarbinol alkylated 3-bromo-9-ethylcarbazole at the 6-position generating 139 (R = Br). Dicarba-zol-3-ylmethanes also resulted from direct treatment of the 3-halo-9-ethylcar-bazoles with formaldehyde-acetic acid and sulfuric acid, presumably via the 3-carbinols. High yield 3-monoalkylation of 9-methylcarbazole was... 

It of interest to note that the isobutyl group may also be replaced by a heterocyclic ring. The route to this compound, pirprofen (51-6), starts with the direct methylation of unesterihed 4-nitrophenylacetic acid (51-1). The observed selectivity for monoalkylation in this case may reside in the structure of the dianion, whose most stable form is presumably that depicted in (51-2). Catalytic reduction of the product (51-3) gives the corresponding aniline this is then converted to its acetanilide (51-4) with acetic anhydride. Treatment with chlorine followed by hydrolysis gives the chloroaniline (51-5). Double alkylation of this last intermediate with 1,4-dichloro-but-2-ene (depicted as the cis isomer for aesthetic reasons) forms the dihydropyrrole ring. There is thus obtained the NSAID pirprofen (51-6) [52]. 

Alkylation of allylic acetates. Rcgioselccti ve monoalkylation of allylic acetates is possible by use of enol stannanes (prepared by reaction of lithium enolates with chlorotri-n-butyltin) in the presence of this Pd complex. The less substituted end of the allyl group is alkylated with formation of the (E)-isomer.4 Examples ... 

The acid-catalyzed hydrolysis of orthoesters is very much faster than that of esters. The second-order rate coefficient for the hydrolysis of ethyl acetate is of the order of 10"4 1-mole-1-sec1 at 25°C, whereas that for the hydrolysis of ethyl orthoacetate103 is of the order of 104 l-mole-1-sec 1, and that for the breakdown of a monoalkyl orthoester must be faster still. If the breakdown of the tetrahedral intermediate is partially rate-determining in acid-catalyzed ester hydrolysis, therefore, its concentration must be very small that is, the equilibrium for its formation must be highly unfavourable. This... 

Initial reports on the use of simple enolates as nucleophiles in TT-allylpalladium chemistry met with only limited success.77 106 The enolate of acetophenone reacted with allyl acetate in the presence of Pd(PPh3)4, but gave predominantly dialkylated product.106 The use of the enol silyl ether of acetophenone gave only monoalkylated product with allyl acetate and Pd° catalysis, but substituted allyl acetates did not function in this reaction.106 Enol stannanes, however, have been found to give monoalkylated products with a wide variety of allyl acetates (equation 19).106 In situ generation of enol stannanes from lithium enolates and trialkylstannyl trifluoroacetates followed by Pd°-catalyzed allylation has been demonstrated.107... 

The use of bis(dibenzylideneacetonato)palladium and l,2-bis(diphenylphosphino)ethane as catalyst was reported to allow efficient monoalkylation of lithium enolates of ketones, with allyl acetates.110 Pd(PPh3)4 and allylammonium salts have also been reacted successfully with lithium enolates.80... 

On the other hand, methylaluminum bis(4-bromo-2,6-di-fert-butylphenoxide) can effect the a-alkylation of enol silyl ethers of a variety of ketones, esters and some aldehydes108. Use of the (Z-Bu)Me2Si group is recommended in the ketene silyl acetal substrates. Use of a less bulky Me3Si or Et3Si group leads to a mixture of monoalkylation products and rearranged a-silyl esters. 

An elegant strategy for the preparation of monoalkylated 1,2- and 1,3-diols is the nucleophilic ring-opening of cyclic acetals by hydride or by other nucleophiles (Scheme 10.12) [46, 56], Not all acetals undergo these reactions cleanly, and careful... 

Platinum oxide has also been used for the preparation of monoalkyl- or monoaralkyl-hydrazines from the corresponding hydrazones.84,85 It is noted that the yields of hydrazines appear to have been improved considerably with use of ethanol-acetic acid as solvent,85 compared to the use of methanol.84... 

In a beautifully straightforward synthesis5 of D-norgestrel (16) (Scheme 3) the key reaction is the transformation of dextrorotatory (13b) into (14) (85%) with paraformaldehyde and benzenesulphinic acid in triethanolamine-acetic acid. To avoid dialkylation at least a 3 1 volume ratio of triethanolamine to acetic acid is needed. Catalytic reduction to (15) followed by reaction with the anion of (5) yielded (6b X = O). Further elaboration produced dextrorotatory norgestrel (16). Monoalkylation of the diones (13) with l,3-dichlorobut-2-ene yields6 the compounds (17) and then, after steps, the laevorotatory ketones (18). 

Cool the mixture to room temperature and filter off the precipitate of the dialkylated malonate derivative. Extract the filtrate with diethyl ether (400 mL). Remove the ether using a rotary evaporator and distil the residue under vacuum using a Kugelrohr apparatus. The monoalkylated product is a colourless oil (b.p. 150°C, 0.1 mmHg), flf = 0.26 (Si02, 20% ethyl acetate/ petroleum ether), 7.8 g (47%). 

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