Substituted 3-diethyl

Anhydrous hydrogen fluonde is a superior reagent for various cyclizations It converts aryl-substituted diethyl arylmalonates into tetralones in good yields [5] (equation 6)... 

Radhakrishna and coworkers showed that DPH Ih reacts with sodium enolates of substituted diethyl malonates to afford a-amino carboxylic acids in good yields (Scheme 13) ". ... 

Fluorinated enamines are hydrolyzed in acid to produce substituted diethyl fluoroacetamides.16... 

Multinuclear NMR data for homologous senes of fluoromethylated malo-nates [72] and trimethylsilanes [97] are compiled in Table 11. In both senes, fluoromethyl attachment is to a quaternary site These compounds are readily synthesized using fluorohalomethanes to incorporate the final fluoromethyl moiety All the malonates, except diethyl methyltnfluoromethylmalonate (4) [93], are isopropyl-substituted diethyl esters [72]. The silane data, with the exception of trimethyltrifluoromethylsilane (5) [95], are from reference 97 Chemical shift data are very comparable, with the malonates having higher proton and fluorine chemical shifts but slightly lower carbon values. The magnitudes of cf and 2J jp coupling are similar for both sets of compounds. 

In a study by Hansch, five mete-substituted diethyl phosphonate esters (12.14) showed cholinesterase inhibition in fruit flies. Correlations between cr-values, ),-values, and both parameters together were explored. The relevant data are included in Table 12.5. 

On the other hand, it is somewhat surprising that the change of the slow step apparently does not affect the Hammett p value (p = —3.25 for the 2-aryl-l,3-dioxolanes, p = —3.35 for the substituted diethyl benzals). However, it is not unlikely that the substituent effects on k n and ftni are nearly equal and cancel each other in the overall substituent effect on feH ... 

Base-induced cycloaddition of diethyl isocyanomethylphosphonate 1326 to trifluoroacetimidoyl chlorides 1327 produces 1-substituted diethyl 5-trifluoromethylimidazole-4-phosphonates 1328 with high regioselectivity (Scheme 339) <19968511>. 

A new method of cyclization has been developed, through the reaction of suitably or//ru-substituted diethyl benzoylphosphonates (41), or their acid chloride precursors, with trialkyl phosphites. An analogous reaction takes place with (42) to give the fluorenylphosphonate (43). The mechanism suggested involves initial attack on carbonyl oxygen, and gains support from the formation of the benzofuranylphosphon-ate (45) in the reaction of (44) with triethyl phosphite. 

The reaction must be carefully controlled in order to optimize the yield. Cycloadditions with substituted diethyl 1-alkynylphosphonates are less satisfactory. ... 

Substituted diethyl l-(ethoxycarbonyl)-l-fluoromethylphosphonates bearing acyL " "" or alkoxycarbonyk groups in a-position, on room temperature treatment with MgCl2/NH4Ck"" or wet silica gel/AcOEt,"" produce the corresponding a-fluoro-P-keto esters and fluoromalonates in very good yields (83-92%, Scheme 3.61). - ... 

The Michaelis-Arbuzov reaction has been extended to substituted bromomethyl epoxides such as cis- and tr(7M.v-l,3-diphenyl-2,3-epoxy-4-brorno-l-but monc andcA-4-benzyloxy-l-bromo-23-cpoxybutane 2 to give the substituted diethyl 23-epoxypropylphosphonates in high yields. 

These two methods are complementary and give access to a variety of carbon-substituted diethyl 2-formylalky Iphosphonates. 

Triethyl phosphite does not react with aldimines in EtOH. However, the addition of HCOgH (1 eq) to the (EtO)3P/aldimine mixture in EtOH induces an exothermic reaction resulting in the exclusive formation of the iminoalkylphosphonate. Undoubtedly, the 1,4-addition of triethyl phosphite is promoted by initial protonation at the nitrogen atom, which activates the double bond toward Michael addition and generates the formate anion for the dealkylation step (Michaelis-Arbuzov reaction). The dialkyl-substituted formylphosphonates are obtained by hydrolysis of the imine function with an appropriate hydrolytic procedure using either 6 M HCl or 1 M oxalic acid. The method provides a simple and convenient access to a broad range of substituted diethyl 2-formyl-alkylphosphonates in satisfactory overall yields (45-80%). ... 

Similarly, the reaction of diethyl 1-formyletliylphosphonate witli diethyl 1-methoxy-l-(meth-oxycarbonyl)methylphosphonate in the presence of NaHMDS in THF at room temperature affords the expected Y-methoxy-P,Y-unsaturated phosphonate in 39% yield. Diethyl 1,1-difluoro-l-formylmethylphosphonate hydrate undergoes an olefination reaction with stabilized methylphosphonate carbanions under a variety of conditions to give 3-substituted diethyl l,l-difluoro-2-propenylphosphonates in 45-78% yields. ... 

Okamoto, Y, and Sakurai, H., Properties of a-substituted diethyl a-ethoxycarbonylphosphonates, Kogyo Kagaku Zasshi, 73, 2664, 1970 Chem. Abstr, 74, 125798, 1971. 

Figure 5.5 shows the relationship between hydrolyzability and anticholinesterase activity for seven substituted diethyl phenyl phosphates. The hydrolysis constants were determined in a buffer of pH 7.6 at 37°C and have the unit min-1. 

N,H4 H,0 (12.0 g) was added to a solution of the appropriate 2-substituted diethyl pyrimidine-4,5-dicarboxylate 1 (0.0397 mol) in MeOH (250 mL) and the mixture was refluxed for 3-4 h. The resulting yellow crystals were filtered to give the hydrazine adducts. The adducts were suspended in HzO (200 mL) and acidified with 10% HC1 with stirring (HOAc was employed in the case of the 2-pyridyl derivative). After the color of the crystals had changed from yellow to colorless, the resulting 2-substituted pyrimido[4,5-r/ pyridazine-5,8-diols were filtered and washed with H2o and MeOH yielding colorless powders. 

The same authors reported a similar reaction of a substituted diethyl ma-lonate with l,9-diamino-3,7-diazanonane to produce the [14]N4 (cyclams) in 25-40% yields (Tabushi et al., 1977). Many other researchers have used the... 

The p-cyanophenyl derivative of [14lN4-diamide was prepared in a 19% yield from the p-cyanophenyl-substituted diethyl malonate (Morphy et al., 1988). Chiral cyclic diamides were prepared from chiral tetraamines in... 

Thermal condensation of pyrazoles with substituted diethyl malonates or triethyl methane-tricarboxylate provides an easy way to 2-substituted derivatives (300). Yields range between 30% and 60% and combined with an easy availability of the malonates this approach could be attractive (Equation (40)) <89S629>. An alternative approach starting from 3,5-dihydroxy pyrazoles and 1,3-dicarbonyl compounds is applicable for a wide range of substituents (Equation (41)) <82JOC295>. 

Heerden and co-workers have reported a convenient synthesis of multifunctional stereodefined dienes 187 using substituted diethyl malonate anions and MBH adducts 186, which were derived from a,p-unsaturated aldehydes (Scheme 3.74). 

The anion of the ylide (103), functioning as a vinyl anion equivalent, undergoes alkylation then elimination of triphenylphosphine to give substituted diethyl fumarates (104). Organocopper species derived from Grignard reagents and the cuprous bromide-dimethyl sulphide complex add stereospecifically to dimethyl acetylenedicarboxylate to give 2-sub tituted maleates. ... 

Oxidation of 4-CF3S substituted diethyl phthalate 137b by C1O3 in AcOH (Scheme 37) leads to sulfone 142 and then through diamide 143 to dinitrile 144 used for preparation of p-tetra(trifluoromethylsulfonyl)plhalocyanine 145 and its... 

Doubly deprotonated methyl 3-nitropropanoate is also useful for the synthesis of a-substituted acrylic esters. These compounds are prepared in good yield from substituted diethyl malonates by alkylation with 1-chloroethyl phenyl sulphide followed by dealkoxycarbOnylation. P-Substituted acrylic esters are readily prepared from the a-cyano-enamine (110) (Scheme 65). ... 

Similar Hammett or Taft correlations have been shown for para-substi-tuted triphenylphosphines (although poor), substituted phenylphosphonic difluorides (Szafraniec, 1974 slope p= —5.96), substituted phenylphosphonic acids (Mitsch et al., 1970), aryl-substituted diethyl phenyl phos-phonates (Mitsch et al., 1970), substituted phenylthiophosphonic dichlorides (where resonance and polar contributions are separated Maier, 1974), and others (Anttimanninen, 1981). In all cases electron-withdrawing substituents lead to increased shielding of phosphorus. If the Letcher and Van Wazer theory is correct (and criticism exists, cf. Kozlov and Gaidamaka, 1972 lonin, 1968 Murray eta/., 1971 Schmidpeter and Schumann, 1970),... 

An efficient and highly enantioselective, organocatalytic aza-Michael addition of JV-substituted diethyl thionophosphoramidates (84) to enones... 

Barbituric acid and 2-thiobarbituric acid are readily prepared by the condensation of diethylmalonate with urea and thiourea respectively, in the presence of sodium ethoxide. The use of substituted derivatives of urea and thiourea and of diethyl malonate will clearly lead to a wide range of barbituric and thiobarbituric acids having substituents in the i, 3, or 5 positions. 

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