Acetylenedicarboxylic acid, addition

Both acetylenedicarboxylic acid and its ester undergo Michael addition reactions with a variety of nucleophilic reagents. An example is... 

Krapcho and Vivelo have described a new formal total synthesis of tropinone (124) and ( )-cocaine (98) (94). Cycloaddition of IV-methylpyrrole (182) and acetylenedicarboxylic acid leads to 183, which is hydrogenated to 184. The diacid mixture 184 is refluxed in MeOH/HCl to yield the diester mixture 185. Addition of this to an excess of metallic sodium in liquid ammonia at — 78°C leads to the N-methylpyrrolidine derivative 186 (cf. 95), whose diethyl analog 147 has earlier been converted to tropinone (124) and (+)-cocaine (98) (78-80) (Scheme 13). 

Further studies on 1,3-dipolar addition reactions of diazophosphonates have been recorded,122 and work on 2-diazo-l-hydroxyalkylphosphonates also continues.123 The ester (155 R = H) reacts with esters of acetylenedicarboxylic acid without liberation of nitrogen to give stereoisomeric C-phosphorylated pyrazolines, which can be decomposed with both phosphorus-carbon and carbon-carbon bond fission, affording mixtures containing dimethyl acetylphosphonate, dimethyl hydrogen phosphonate, and tri(alkoxycarbonyl)pyrazolines. In the reaction between the same diazophosphonate and diazomethane, the latter conceivably acts as a basic catalyst for proton transfer in a series of steps which includes phosphonate-phosphate isomerization. The importance of a labile proton is demonstrated by the fact that the ester (155 R = Me) does not react in the manner described above. 

Dihydronaphthalen-1,4-iwmes from Isoindoles The naphthalen-l,4-imine derivatives 91-99 have been obtained by addition of acetylenedicarboxylic esters to the appropriate isoindoles. 3- ss Some such adducts react further with acetylenic esters (see Sections III, G and H), so that A -ethyl- and A-n-butylisoindole give 1 2 adducts with dimethyl aoetylenedicarboxylate instead. iV-Methylisoindole appears to be exceptional in giving an oily 2 1 adduct, for which structure (100) was suggested on analogy with the 2 1 adduct obtained from l,3-diphenylbenz[c]furan and acetylenedicarboxylic acid. ... 

Ethyl mercaptan reacts with DMAD to give a 1 1 adduct through a trans mode of addition. WeibulP has reported that a mixture of both fumarate and maleate is formed from cyclohexyl mercaptan with propiolic acid. A similar observation has been made in the reaction of cyclohexyl mercaptan with acetylenedicarboxylic acid. ... 

A small number of pyrroles undergo addition of acetylenedicarboxylic acid across the 2,5 positions, yielding adducts similar to those derived from cyclopentadiene. For instance, 1-benzylpyrrole (1) gives some 4,69,70 but it is not known if the product is formed via a species such as 2 or by a concerted addition. 

Having sufficient amounts of these novel dienes in hand opens the field for further study. Cycloaddition of acetylenedicarboxylic acid dimethyl ester (ADDE) to [3]dendralene 7 in toluene first afforded the l l-adduct 43, which by a second addition of ADDE provided the expected 2 l-adduct 44. After this had been aromatized by treatment with DDQ to the naphthalene derivative 45, a double benzannulation could be carried out as described in Scheme 8 [13]. 

Elad, D. The Light-induced Addition of Formamide to Esters of Maleic, Fumaric, and Acetylenedicarboxylic Acids. Proc, chem. Soc. 1962, 225. 

A series of 2-phenyl l,3-selenazolidin-4-ones 257 is readily prepared from selenobenzamides 255 upon treatment with dimethyl acetylenedicarboxylate (DMAD) in ethanol or methanol <07JHC231>. Under similar conditions, reaction of 255 with acetylenedicarboxylic acid affords the 4-ethoxy-4,5-dihydro-selenozol derivative 259 where the ethoxyl group is introduced to the C-4 position from the ethanol solvent via nucleophilic addition. 

The reactions of trialkyl phosphites with dialkyl acetylenedicarboxylates have been studied in some detail, and the products explained as proceeding via 1 1 intennediates. Thus, the addition of a solution of dimethyl acetylenedicarboxylate to either (MeO 13 or (EtOjjP (2 eq) at 0°C leads to the formation of the corresponding 1,2-diphosphoranes. Treahnent of the diphosphorane with anhydrous HBr leads to protonation and subsequent dealkylation to give tetramethyl l,2-/ (meth-oxycarbonyl)-l,2-ethylenediphosphonate in 94% yield (Scheme 8.49). Trialkyl phosphites add vigorously to acetylenedicarboxylic acid in EtjO to give tetraalkyl 1,2-Z z5 (alkoxycarbonyl)-1,2-ethylenediphosphonates in modest yields. ... 

Nitrile, azo, and nitroso groups, and even the oxygen molecule, take part in such reactions, and acetylenic triple bonds in particular confer reactivity as philodiene. As for dienes, so for philodienes the reactivity depends on the constitution. Activating groups particularly favor addition. The most reactive components include <%,/ -unsaturated carbonyl compounds such as acrolein, acrylic acid, maleic acid and its anhydride, acetylenedicarboxylic acid, p-benzo-quinone and cinnamaldehyde, as well as saturated nitriles and <%,/ -unsaturated nitro compounds. Tetracyanoethylene also reacts with dienes.41,42 Conjugation of the double bond to an active group is not absolutely essential for a philodiene, for dienes add under certain conditions also to philodienes with isolated double bonds examples of the latter type are vinyl esters and vinyl-acetic acid. Ketenes do not undergo the Diels-Alder reaction with dienes, but instead yield cyclobutanone derivatives 43,44... 

Condensation of alkynes with carboxylic acids. Addition of RC(X)H to alky-nes forms enol carboxylates. On the other hand, heterocyclization occurs with acetylenedicarboxylic esters. ... 

Like the esters of acetylenedicarboxylic acid (6), dicyanoacetylene (2) has often been employed in cycloaddition reactions it participates in Diels-Alder and 1,3-dipolar cycloadditions, and ene reactions as well as homo additions are also known [9,11], Although kinetic measurements with 2 seem not to have been performed so far, from working knowledge it appears that 2 is a more reactive dienophile than any other activated acetylene including hexa-... 

Addition of carboxylic acids to alkynes generally requires the presence of strong protic acids or other electrophilic catalysts. It was, however, observed that carboxylic acids having pAa < 4.5 do add to phenylacetylene in the absence of a strong acid catalyst to give enol esters In case of formic acid, addition occurred by simply heating the alkyne in formic acid at 100 C. A variety of diaryl, dialkyl, aralkyl and terminal alkynes react, but dimethyl acetylenedicarboxylate was found to be unreactive. The final product is a ketone, while a stoichiometric amount of carbon monoxide is released. 

Besides acrylic (Ac) and methacrylic acids, maleic, fumaric, itaconic, ethyleneglycolmethacrylatephthalic and acetylenedicarboxylic acids are used. Different complications, which are important for polymerization processes, are often observed during these syntheses. Among them should be noted the possibility of the formation of mono- and dihydrates (which are sometimes crystalline), the formation of acid salts with additional coordination of acid... 

The cationic complex (VII, X = Cl) forms a symmetrical ( Pnmr i.r.) complex with diphenylacetylene, which is very labile. The complexes [Rh2Cl2(/Lt-CO)(/Lc-acet)(dppm)2], where acet is hexafluoro-2-butyne or acetylenedicarboxylic acid dimethyl ester, are also symmetrical, and the acet ligand is coplanar with the rhodium atoms. The C C bond length is increased to 1.32 A, and so the complex is truly described as a cis-dimetallated alkene. Comparison with the reactions with CO suggests that the activation of an alkyne (or alkene) to hydrogenation may occur when the alkyne is initially coordinated to the catalyst at a terminal position, e.g., (XII), with subsequent oxidative addition and hydrogen transfer steps. A complex of the type (XII) may instead be only a minor but active component of a solution of which the alkyne-bridged complex is the major but less active component. ... 

Addition of bromine to acetylenedicarboxylic acid, for example, gives the trans isomer in... 

The products of the reaction of acetylenedicarboxylic acid esters with 4,5-dihydro- 1 //-pyrazole-1 -carbothioamides and 3,4,5,6-tetrahydro-2/f-1,2,4-triazepine-3-thiones have been characterized by Danilkina et by the use of NMR parameters including Vhc and couplings. In particular, the /h5C4 couplings of 5.0 Hz observed for methyl esters of (2Z)-[2-(3-methyl-4,5-dihydro-l TZ-pyrazol-1-yl)-4-oxo-1,3-thiazol-5(4//)-ylidene]ace-tic acids have provided evidence that the exocyclic double bonds in these compounds are of the Z configuration, which corresponds to the mechanism reported by the authors for the trans addition of the SH group to the triple bond in DM AD. 

The structure of the condensation products of thioureas and dimethyl acetylenedicarboxylate had not been assigned with certainty. This problem has now been resolved, in one case, by 2f-ray analysis. Thus the addition of iV-thiocarbamoylpiperidine to the acetylenic reagent, which may theoretically give rise to six isomeric products, yields in fact 5-methoxy-carbonylmethylene-2-piperidino-2-thiazolin-4-one, having the geometrical configuration shown in (166). Confirmation has also been provided that the reaction of thiourea with bromosuccinic, maleic, fumaric, or acetylenedicarboxylic acids yields, in each case, a 2-thiazoIine, e.g. (167). ... 

Preparative Method prepared by the addition of methyl isothiocyanate to acetylenedicarboxylic acid (ethanol, 25 °C) to afford a 6 1 mixture of 2-(methylthio)fumaric and -maleic acids, which are dehydrated by dissolution in thionyl chloride for 1 h at 25 °C, then 7 h at 60 °C. Excess SOCI2 is removed at 120 °C at aspirator pressure, followed by distillation of the residue to afford the crystalline anhydride in 68-77% yield. ... 

Nonetheless, furan does react with bromine in methanol to produce the corresponding addition compounds, (E)- and (Z)-2,5-dimethoxy-2,5-dihydrofuran (Equation 8.55) and aromaticity can also be lost through a Diels-Alder reaction of furan and substituted furans with reactive dienophiles such as the diethyl ester of acetylenedicarboxylic acid (Equation 8.56)... 

Table 1 shows the predicted activation barriers for the addition of acetylenedicarboxylic acid to cyclopentadiene. As indicated by these numbers, HF (Hartree-Fock) significantly overestimates the activation barrier and MP2 underestimates it. The integrated methods provide much more accurate activation barriers. The method and size effects are included in this... 

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