A,/ -Acetylenic acids

These studies were extended to the a,/ and y-hydroxy-a,/ -acetylenic acids (61a), (81). We found that the direct carbonation of the sodium salts of thienylacetylenes or of acetylenic carbinols was of no avail even under pressure using various solvents. Small amounts of 2-thenoic acids were isolated only. However, a, -acetylenic acids as well as the... 

As for the unsaturated carbonyl compounds, the most significant groups are the oc,/ -unsaturated acids or esters. Some of their methods of formation are closely analogous, for example, (a) the Horner-Emmons or Wadsworth-Emmons reaction, and (b) the aldol-type reactions. Rather more specific methods are considered below for the formation of a,/ -acetylenic acids, and for the conversion of the unsaturated dicarboxylic acid, maleic acid, into its anhydride or into fumaric acid. 

A useful route to a,/(-acetylenic acids, illustrated by the preparation of but-2-ynoic acid (Expt 5.217), involves the base-induced decomposition of the dibromopyrazolone which is obtained by brominating pyrazol-5-one, which is itself prepared by the reaction of a / -keto ester with hydrazine. 

Direct proof of the biological validity of this type of decarboxylation was afforded by enzymatic decarboxylation of an a-acetylenic acid. Gardner et al, (1961) incubated the ten-carbon a-acetylenic acid (XXXVIII) with a cell free extract of Coprinus quadrifidus mycelium and isolated from the extract a compound (XXXIX) containing one less carbon and a free ethynyl group. 

Table 1 7 shows that hydrocarbons are extremely weak acids Among the classes of hydrocarbons acetylene is a stronger acid than methane ethane ethylene or benzene but even its K is 10 ° smaller than that of water... 

The direction of addition, verified by acetylene oxidation into a known acid, proves that the nitiilimine carbon atom adds to the terminal atom of the enyne system, which is inconsistent with the assumed polarization of the unsaturated compound H2C=CH—C=C—R from the vinyl group towardR. The authors explain this by a possible transfer of the reaction center in nitrilimine as a particle with a nucleophilic center on a carbon Ph—C=N" —N —Ph Ph—C =N =N—Ph (63ZOB3558). 

Strategy In comparing two acids, the one with the lower pKz is stronger. Thus, water is a stronger acid than acetylene and gives up H+ more easily. 

Solution Because water is a stronger acid and gives up H+ more easily than acetylene does, the HO" ion must have less affinity for H+ than the HC=C ion has. In other words, the anion of acetylene is a stronger base than hydroxide ion, and the reaction will not proceed as written. 

In the analogous studies of the photolysis of sulfolane (31), the work of Honda and coworkers66 was carried out in the gas phase at 70-130 °C and established the formation of S02, ethylene, cyclobutane and acetylene as the major products, on mercury-sensitized photolysis. In considerable contrast, photolysis of sulfolane at 185 nm in the liquid phase67 produced ethylene( = 0.22), the sultine (32) (parallel experiments on aqueous solutions of sulfolane, a sulfinic acid is also believed to be formed. The authors believe that both four-membered (33) and six-membered (32) sultines may be formed during these photolyses. Further work in this area would appear to be necessary to unravel the full mechanistic details. 

Thermal [2h-2] cycloaddition reactions of carbonyl compounds were catalyzed by a Lewis acid. The catalyst forms complexes with the carbonyl compounds and enhances the electron-accepting power. The reaction shifts from the delocalization band to the pseudoexcitation band. Catalyzed [2h-2] cycloaddition reactions were observed with acetylenic compounds [28] and ketenes [29-31]. 

Some preparations of alkene and acetylenic compounds from alkene and acetylenic starting materials can, in principle, be classified in either the monofunctional or difunctional sections for example, the transformation RCH=CHBr — RCH=CHCOOH could be considered as preparing carboxylic acids from halides (Section 25, monofunctional compounds) or preparing a carboxylic acid-alkene (Section 322, difunctional compounds). The choice usually depends on the focus of the particular paper where this reaction was found. In such cases both sections should be consulted. 

Oxazolium oxides, which can be generated by cyclization of a-amido acids, give pyrroles on reaction with acetylenic dipolarophiles.144 These reactions proceed by formation of oxazolium oxide intermediates. The bicyclic adduct can then undergo a concerted (retro 4 + 2) decarboxylation. 

Enzymic Decarboxylation of an a,/S-Acetylenic Acid. J. Chem. Soc. [London] 1961, 1532. 

It occurs with the alkyls, aryls or acetylides of metals more electropositive than magnesium, but including Grignard reagents, and is often carried out by adding a solution of the organometallic compound in an inert solvent to a large excess of powdered, solid C02 it is a particularly useful method for the preparation of acetylenic acids. The Kolbe-Schmidt reaction (p. 291) is another example of carbanion carbonation. 

Standard procedure used a mixture of 0.26 mmoles acetylenic acid, 20 mg (0.005 mmoles) catalyst in acetonitrile (1.2 mol L"1) that was stirred under air atmosphere at 40°C. After completion of the reaction, the mixture was centrifugated and the solvents... 

Acetylene is sufficiently acidic to allow application of the gas-phase proton transfer equilibrium method described in equation l7. For ethylene, the equilibrium constant was determined from the kinetics of reaction in both directions with NH2-8. Since the acidity of ammonia is known accurately, that of ethylene can be determined. This method actually gives A f/ acid at the temperature of the measurement. Use of known entropies allows the calculation of A//ac d from AG = AH — TAS. The value of A//acij found for ethylene is 409.4 0.6 kcal mol 1. But hydrocarbons in general, and ethylene in particular, are so weakly acidic that such equilibria are generally not observable. From net proton transfers that are observed it is possible sometimes to put limits on the acidity range. Thus, ethylene is not deprotonated by hydroxide ion whereas allene and propene are9 consequently, ethylene is less acidic than water and allene and propene (undoubtedly the allylic proton) are more acidic. Unfortunately, the acidity of no other alkene is known as precisely as that of ethylene. 

Acetylacetanilid, a24 Acetyl acetate, a22 Acetylacetone, p34 A-Acetylanthranilic acid, all Acetylbenzene, a31 Acetylcyclopropane, c410 Acetylene dichloride, d228, d229... 

Simple reaction occurs with aryl halides only when the ring is sufficiently substituted with electron-withdrawing functions to allow attack by the nucleophilic phosphorus.53-56 Generally, reaction with aryl halides requires the presence of a Lewis acid catalyst or some other means of reaction initiation. These reactions will be considered in detail in Chapter 6 of this work. Interestingly, while reactions involving vinylic halides seem to correlate with those of aromatic halides (see Chapter 6), acetylenic halides undergo facile reaction with these phosphorus reagents.57 58... 

Addition of lithium derivatives of acetylenides (Li—C=C-C02R) to chiral nitrones proceeds with high stereoselectivity, giving a-acetylene substituted hydroxylamines (410a,b) (656). This reaction has been successfully applied to the synthesis of y-hydroxyamino-a, 3-ethylene substituted acids (411a,b), formed in the reduction of (410) with Zn in the presence of acid (657, 658), and to chiral 5-substituted-3-pyrroline-2-ones (412a,b) (Scheme 2.184) (658). 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

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