2- malonic acid formation

It can be assumed that the small amount of piperidine in the reaction mixture is completely protonated by malonic acid because piperidine is more basic than pyridine. Hence, only the pyridine is available for the formation of the enolate of malonic acid (formation of enolate D, Figure 10.49), of the enolate of the monocarboxylate B (formation of enolate E), or of the enolate of the dicarboxylate C (formation of F). Pyridine reacts with any of these C,H acids in an equilibrium reaction ... 

Malonic acid condenses with most aldehyde and some very reactive ketones to give either the alkylidine (or arylidine) malonic acids or the corresponding monocarboxylic acrylic or cinnamic acids. The alkylidine (or arylidine) malonic acids are best produced using ammonia in alcohol at 70 °C or below. Pyridine is the solvent and base of choice (Verley-Doebner modification) for the synthesis of a,p-unsaturated acrylic or cinnamic acids, " while piperidinium acetate in refluxing xylenes is preferred for the selective synthesis of the P,y-isomers. With malonic acid, formation of bis-adducts by Michael addition of an additional equivalent of the active methylene is rare. ... 

The reaction is readily illustrated by the formation of crystalline sorbic acid by the condensation of crotonaldehyde and malonic acid in hot pyridine solution ... 

Reaction of chloroacetic acid with cyanide ion yields cyanoacetic acid [372-09-8] C2H2NO2, (8) which is used in the formation of coumarin, malonic acid and esters, and barbiturates. Reaction of chloroacetic acid with hydroxide results in the formation of glycoUc acid [79-14-1]. 

Triiodoacetic acid [594-68-3] (I CCOOH), mol wt 437.74, C2HO2I3, mp 150°C (decomposition), is soluble in water, ethyl alcohol, and ethyl ether. It has been prepared by heating iodic acid and malonic acid in boiling water (63). Solutions of triiodoacetic acid are unstable as evidenced by the formation of iodine. Triiodoacetic acid decomposes when heated above room temperature to give iodine, iodoform, and carbon dioxide. The sodium and lead salts have been prepared. 

C2S2, is a red Hquid (mp —0.5° C, bp 60—70°C at 1.6 kPa (12 mm Hg)) produced by the action of an electric arc on carbon disulfide (1 4). The stmcture has been shown to be S=C=C=C=S on the basis of its reactions to form malonic acid derivatives and on the basis of physical measurements. It is unstable and decomposes ia a few weeks at room temperature it decomposes explosively when heated rapidly at 100—120°C with formation of a black polymeric substance (C2S2) (5,6). Dilute solutions ia CS2 are fairly stable, but photochemical polymerisation to (C2S2) occurs. 

One such compound, bropirimine (112), is described as an agent which has both antineo-plastic and antiviral activity. The first step in the preparation involves formation of the dianion 108 from the half ester of malonic acid by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the more nucleophilic carbon anion to give 109. This tricarbonyl compound decarboxylates on acidification to give the beta ketoester 110. Condensation with guanidine leads to the pyrimidone 111. Bromination with N-bromosuccinimide gives bropirimine (112) [24]. 

Decarboxylation is not a general reaction of carboxylic acids. Rather, it is unique to compounds that have a second carbonyl group two atoms away from the —COoH. That is, only substituted malonic acids and /3-keto acids undergo loss of CC>2 on heating. The decarboxylation reaction occurs by a cyclic mechanism and involves initial formation of an enol, thereby accounting for the need to have a second carbonyl group appropriately positioned. 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

The aromatic spacer group of the model receptors prevent the formation of intramolecular hydrogen bonds between the opposing carboxyls yet these functions are ideally positioned for intermolecular hydrogen bonds of the sort indicated in 32. The acridine derivatives do indeed form stoichiometric complexes with oxalic, malonic (and C-substituted malonic acids) as well as maleic and phthalic acids, Fumaric, succinic or glutaric acids did not form such complexes. Though protonation appears to be a necessary element in the recognition of these diacids, the receptor has more to... 

One of the most recent developments in the field of Ni-catalyzed reactions of alkyl halides with organozinc derivatives is a study of Terao et al.411 They reported the use of three additives in the couplings 1,3-butadiene, N,N-bis(penta-2,4-dienyl)benzylamine 308a, and 2,2-bis(penta-2,4-dienyl)malonic acid dimethyl ester 308b. Addition of tetraene 308b to the reaction mixtures significantly increased the product yields (Scheme 157). The remarkable effect of these additives was explained by the formation of the bis-7r-allylic complex 309 as the key intermediate (Scheme 158). 

Nitrition of ketones 313 and malonic acid diamide 312 also leads to the formation of furoxans 314 (Scheme 78) C1999CHE1415, 2004T1671, 2005MRC563>. 

Condensation of coumaric acid with malonic acid yields the basic chalcone and stilbane skeletons (see Fig. 3.6). Stilbenes are found in most vascular plants, where they exhibit fungicidal and to a lesser extent antibiotic properties. They function as both constitutive and inducible defense substances. Some stilbenes inhibit fungal spore germination and hyphal growth, whereas others are toxic to insects and parasitic nematodes (round-worms). They also possess antifeeding and nematicide properties in mammals. For example, resveratrol (a stilbene in red wine) suppresses tumor formation in mammals. 

Consider now what happens when the two carboxyl groups react to form a small ring, for example the anhydride. The angle between the carboxyl carbons must be reduced much further, perhaps to around 90°, in the product and in the transition state leading to it. Compared with malonic acid itself, this process has less far to go in the dimethyl compound because the two alkyl groups have already forced the carboxyls part of the way towards each other. The observed diminution in bond angle caused by the introduction of the two alkyl substituents thus specifically favours the formation of the small ring. 

The enzymatic reaction was performed at 30 °C for 2 hours in a volume of 1 ml of 250 mM phosphate buffer (pH 6.5) containing 50 mM of KOH, 32 U/ml of the enzyme, and [1- C]-substrate. The product was isolated as the methyl ester. When the (S)-enantiomer was employed as the substrate, C remained completely in the product, as confirmed by C NMR and HRMS. In addition, spin-spin coupling between and was observed in the product, and the frequency of the C-O bond-stretching vibration was down-shifted to 1690 cm" (cf. 1740 cm for C-O). On the contrary, reaction of the (R)-enantiomer resulted in the formation of (R)-monoacid containing C only within natural abundance. These results clearly indicate that the pro-R carboxyl group of malonic acid is ehminated to form (R)-phenylpropionate with inversion of configuration [28]. This is in sharp contrast to the known decarboxylation reaction by malonyl CoA decarboxylase [1] and serine hydroxymethyl transferase [2], which proceeds with retention of configuration. 

Both CO2 activation and enolate formation are combined in the preparation of malonic acid derivatives. The reaction of CO2 with methacrylic esters or methacry-lonitrile and under visible light irradiation produced the corresponding aluminum porphyrin malonate complex. When diethylzinc was added to this system, Al(TPP)Et could be regenerated by axial ligand exchange reactions, and the malonic acid derivatives were formed catalytically with respect to the aluminum porphyrins in a one-pot photosynthetic route (Scheme 1). The first step in this... 

Alkylation of enolate is an important synthetic method.27 The alkylation of relatively acidic compounds such as /i-dikctoncs, /i-ketoesters, and esters of malonic acid can be carried out in alcohols as solvents using metal alkoxides as bases. The presence of two electron-withdrawing substituents facilitates formation of the enolate resulting from removal of a proton from the carbon situated between them. Alkylation then occurs by an Sn2 process. Some examples of alkylation reactions involving relatively acidic carbon acids are shown in Scheme 1.5. These reactions are all mechanistically similar in that a... 

The preformation of carbazol-9-ylpotassium (sodium) has been much less used for the introduction of acyl groups onto nitrogen examples are the formation of 9-methoxy- and 9-ethoxy-carbonylcarbazoles, the dithio-carbamate salt 51, and the malonate 52 by reaction with the alkoxy-chloroformates, carbon disulhde, and malonic acid half-acid chloride, respectively. 

Treatment of the hydrazide 59 with ethyl orthoformate causes an intramolecular N-acylation resulting in the tetracycle 60. The conversion of 1,4-diphenylcarbazole into 61 using N-methylformanilide-phosphorus oxychloride at 95°C must involve an oxidation at some stage. Heating car-bazole with diphenyl 2-benzylmalonate, diethyl 2-ethylmalonate, or malonic acid-phosphorus oxychloride produced the tetracycles 62 (R = PhCH2, Et, and H, respectively). It is not clear whether the N-9 or the C-1 acylations required for the formation of 62 occur first, although it is likely that the initial attack is at the nitrogen. 

---