Dialkyl dicarboxylate

This synthetic route is based on ring closure by Dieckmann condensation of 1,2-bis-carbalkoxyalkylpyrrolidines. It has gained special importance during the last few years, after application to several total syntheses of naturally occurring pyrrol izidine bases. The usual starting compounds employed in this route are esters of a-pyrrolidineacetic acid, proline, and their homologues, which are converted into N-substituted dialkyl dicarboxylates. The esters of the dicarboxylic acids are subjected to Dieckmann condensation and subsequent ketonic hydrolysis the resultant ketones are used in further reactions. 

An interesting result has been observed when 4-formylantipyrine 89 was converted into the corresponding pyridinium salt 90 and reacted with alkyl 3-aminobut-2-enoates. Tire expected 1,4-dihydropyridines 91 are transient species in these syntheses and readily lose the 4-substituent (antipyrine, 93) so that dialkyl 2,6-dimethylpyridine-3,5-dicarboxylates 92 are obtained (85-95%) (94H815). Protonation of the pyrazole ring by the evolved hydrochloric acid accounts for this particular behavior (Scheme 29). 

Many other reactions have been reported for the synthesis of polyesters, such as reactions between dicarboxylic acid salts and dialkyl halides, reactions between... 

Dialkyl esters of cystine (39) and lanthionine (40) undergo a surprising thermolysis reaction at between 25 C and 80 °C to afford cis and trans methyl 2-methylthiazolidine-2,4-dicarboxylates (43) in protic solvents. A two stage process is proposed for this transformation. An initial i-elimination reaction gives the thiol (41) and the enamine (42). Thiol addition to the imine tautomer of (42) is then followed by loss of ammonia and an intramolecular cyclisation to give (43) <96CC843>. 

Scheme 7.8. Synthesis of dialkyl A/-alkoxycarbonyl-a,(3-unsaturated dicarboxylates.

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

Bouvier, C. Cote, G. Cierpiszewski, R. Szymanowski, J. Influence of salting-out effects temperature and the chemical structure of the extractant on the rate of copper(II) extraction from chloride media with dialkyl pyridine dicarboxylates. Solvent Extr. Ion Exch. 1998, 16, 1465-1492. 

The first example of allylation of imines using dialkyl 2-allyl-l, 3-dioxaborolane-4,5-dicarboxylates 110 or fi-allyldiisopinocamphcnyl borane 154 was reported in 1995." After hydrolysis of the reaction product, homoallyl primary amine was obtained in 54-90% yield and up to 73% ee (Scheme 3-52). 

ABS AE AE/P AES AG AOS APEO APG AS BiAS BM c6(EO)3 CNPEC CTAS D DATS DCPEG DEEDMAC branched alkylbenzene sulfonate alcohol ethoxylate alcohol ethoxylate/propoxylate alkylether sulfate alkyl glucamide a-olefin sulfonate alkylphenol ethoxylate alkyl polyglucoside alkyl sulfate bismuth active substances alkyldimethylbenzyl ammonium triethylene glycol monohexyl ether carboxylated nonylphenoxy carboxylates cobalt thiocyanate active substances R2S10(o.5)2 dialkyl tetralinsulfonate dicarboxylated PEG ditallow ester of di(hydroxyethyl)dimethyl ammonium chloride... 

Ley developed an efficient tandem organocatalytic synthesis of chiral dialkyl 3-alkyl-l,2,3,6-tetrahydropyridazine-1,2-dicarboxylates 272 from /3-oxohydrazines 271. Compound 271 was obtained from commercially available achiral aldehydes and dialkyl azodicarboxylates using (6)-pyrrolidinyl tetrazole as the chiral catalyst. This synthesis proceeds with good to excellent yields (58-89%) and enantioselectivities (69-99% ee). The highest ee values are obtained for the most bulky di-/-butyl azodicarboxylate and the shortest branched aldehydes (Scheme 67) <2006SL2548>. 

In the reactions of benzoyl isothiocyanate 324 and dialkyl acetylenedicarboxylates 325 in the presence of triphenyl-phosphine, 2-phenyl-4-thioxo-47/-l,3-oxazine-5,6-dicarboxylates 326 and dialkyl 2-(benzoylimino)-5-phenyM//-[l,3]dithiolo[4,5- ]pyrrole-4,6-dicarboxylates 327 were formed in a ratio of 1 3 (Equation 30) <2006TL2953>. 

As an alternative to the Glu and Asp scaffolds, the A-(dialkyl)amide of diglycolic acid has been proposed (13). This is readily prepared by heating equivalent amounts of diglycolic anhydride and, for example, bis(octadecyl)amine in refluxing toluene for 48 hours followed by recrystallization from chloroform (mp 81-82 °C)J178 In a similar mode, polyoxyethylene of selected chain length has been used to prepare dicarboxylic acids which, upon mono-amidation with bis(alkyl)amines, yield lipo moieties (e.g., 14) that are coupled to selected amine groups of peptides to produce the peptide amphiphiles. 179180 ... 

The same kind of dialkylation of the dianion 16 also gives cyclobutane or cyclopentane dicarboxylates when dlbromoethane or dibromopropane are used (see Table 6). 

Leaving groups other than halides are also suitable for this type of geminal dialkylation reaction. Thus, diethyl spiro[3.4]oct-6-ene-2,2-dicarboxylate (5) is isolated in 75% yield from the reaction between diethyl malonate and 3-cyclopentene-1,1-dihydroxymethyl di-4-bro-mobenzenesulfonate (4).19... 

Acceptable yields have been obtained for dialkyl 3,3-dimethoxycyclobutane-l,l-dicarboxylates which are functionalized at Cl and C3 by reaction of l,3-dibromo-2,2-dimethoxypropane (10) with malonic esters.22 In these reactions, dimethylformamide proves to be the solvent of choice, because it allows the volume of the reaction mixture to be kept to a minimum.22 High temperature (120 to 130 C) is also necessary for these reactions due mainly to the solubility... 

HEXAHYDRO - 4a,5 - DIMETHYL - 2(3H) - NAPHTHALE-NONE and 2-TRIMETHYLSILYLOXY-1,3-BUTADIENE AS A REACTIVE DIENE DIETHYL trans -4-TRIMETHYL-SILYLOXY-4-CYCLOHEXENE-1,2-DICARBOXYLATE. Sulfur substitution also continues to be of high interest, and three preparations on sulfide synthesis are included BENZYL SULFIDE DIALKYL AND ALKYL ARYL SULFIDES NEOPENTYL PHENYL SULFIDE and UNSYMMETRICAL DIALKYL DISULFIDES sec-BUTYL ISOPROPYL DISULFIDE. 

Parameters required for the description of polyesters I are taken from a recent paper (Abe, A, J. Am. Chem. Soc. 1984, 106, 14) which dealt with the dipole moments of dialkyl esters of dicarboxylic acids. Since the ester groups are all assumed to be in the trans configuration, short-range interactions between consecutive rigid cores are unimportant. As for the rotation around the O-C — C-C bond, the six-state scheme (termed model I in the above paper) is employed. The statistical weight parameter a representing the relative importance of the reversed ester conformations with respect to the normal ones is set equal to unity. The three-state scheme (termed model II) proposed alternatively in the above reference is examined for chains with n = 5 and 6 for comparison. In this model the C O /CC eclipsed form is assumed to be intrinsically more stable than the C 0 /CH form a stabilzation energy E( 1) of 5.0 kj mol-1 is adopted. 

Pyrrole- and indole-carboxylic acid chlorides react with dialkyl- and diaryl-cadmium to yield the ketones and it is noteworthy that the reaction of the anhydride of indole-2,3-dicarboxylic acid with diphenylcadmium produces 3-benzoylindole-2-carboxylic acid and not its isomer (53JCS1889). The ability of l-methylindole-2-carboxylic acid to react with nucleophiles is enhanced by conversion into the mixed anhydride with methanesulfonic acid. The mixed anhydride reacts with carbanions derived from diethyl malonate and from methyl acetate to yield the indolyl (3- keto esters (80TL1957). 

Dialkyl 7-aryl-6,9a-dimethyl-2,3,4,8,9,9a-hexahydropyrido[2,l-h][l,3]-oxazine-7,9-dicarboxylates exhibit long-term antihypertensive-brady-cardic, anti-inflammatory, and spasmolitic effects (92MI1). 

Liquid crystal polyesters are made by a different route. Because they are phenolic esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenolic hydroxyl groups are acylated with a lower aliphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxylic acid, sometimes in the presence of a catalyst. The phenolic polyester forms readily as the volatile lower acid distills from the reaction mixture. Many liquid crystal polymers are derived formally from hydroxyacids (97,98) and their acetates readily undeigo self-condensation in the melt, stoichiometric balance being automatically obtained. 

R1 = N3 R2 = OH) were useful compounds (see Section II,D). The starting materials 55 had been synthesized via Diels-Alder reaction of acetylene-dicarboxylic acid with 2,3-dialkyl-1,3-butadienes, followed by oxidation (85USP4532301 85USP4556512). Yoshida et al. condensed the doubly cross-conjugated cyclopentadiene 57 with hydrazine to obtain 1,2-diazocine 58 (84TL4223) (For structural studies of 58, see Section II,B.)... 

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