2- Bromo-2- malonates

Under the previous conditions, diethyl (amino)phenylmethylenemalo-nate (313) was also obtained in 35% yield in the reaction of diethyl bromo-malonate and benzonitrile (85TL2603). 

Hydroxy benzo[6]thiophene-4-carboxaldehyde, which is prepared from 5-hydroxybenzo[6]thiophene by the Duff reaction 338 or, better, by a modified Gattermann reaction,340 reacts with diethyl bromo-malonate to give the thienobenzofuran (282), and undergoes the Perkin reaction to give the thienobenzo-a-pyrone (283).338... 

Other methods of preparing cyclopropane-modified C q fullerenes using diethyl bromo-malonate are described (1). 

Fig. 2 The first mechanistic diagram of the BZ reaction. X is HBr02 or Br02 and BMA is bromo-malonic acid.

In addition dimethyl allyl(bromo)malonate (4%) and dimethyl bromomalonate (35%) were formed. 

The importance of the nucleophilicity of the heteroatom for product partitioning is shown for the interaction of ethyl diazoacetate with allyl halides, e.g. formation of 29 and 30. In contrast to the result for this diazo compound, rhodium-catalyzed reaction of diethyl di-azomalonate with allyl bromide yields practically no cyclopropane [Rh2(OAc)4 diethyl al-lyl(bromo)malonate (86%) and diethyl 2-bromomethylcyclopropane-l,l-dicarboxylate (6%) RhjCCO) 72 and 10%].2 ... 

The past decade has witnessed the chemistry of fullerene unfold (42-45). Our research group was successful in incorporating a [60]fullerene unit into lipid molecules. Several saturated and unsaturated dialkyl methano-fullerene lipids were synthesized. This was achieved by reaction of [60] fullerene with long-chain dialkyl bromo malonates (Scheme 4) (46). In these fullerene lipids, the cyclopropane system was... 

B-Z reaction using ferroin as a catalyst has been used for pattern formation studies for such a system. According to FKN mechanism, HB1O2 is the autocatalytic species. On commencement of autocatalysis the [Br ] is depleted to a value lower than the critical value. The autocatalytic production of HBrOj is accompanied by oxidation of ferroin to firrin Fe(phen3) +. Br formation occurs due to reaction of Fe(phen3) with bromo-malonic acid. Thus, a differential flow between HBr02 and Br can be achieved. 

A range of aromatic and heteroaromatic nitroalkenes reacted smoothly with ethyl as well as methyl hromomalonates to give the corresponding cyclopropanes in high yields and enantioselectivities (85-99% ee). To explain the stereoselectivity of the process, the authors have proposed that the bromo-malonate was activated by the nickel catalyst through a bidentate fashion. Then, the bromomalonate anion attacked the Si face of the double bond of the nitroalkene, as shown in the transition state depicted in Scheme 2.43. 

MA and BrMA are shorthand for malonic acid and bromo-malonic acid respectively, Fe + and Fe + are shorthand for ferroin and ferriin respectively, and the factor h in reaction R9 is a stoichiometric parameter. The initial... 

Active methylene compounds are very reactive nucleophiles and their halo-derivatives are actively used for catalytic asymmetric cyclopropanation through the MIRC process. Rios and coworkers demonstrated catalytic asymmetric cyclopropanation between 2-bromo malonate and unsaturated aldehydes in the presence of proline-derived organocatalyst 2 (Scheme 1.1) [4]. The reaction smoothly progressed in chloroform at room temperature (rt) and highly enantioselective cyclopropanation was achieved. 

Sodium hydride (9.3 g, 0.22 mol) was washed with petroleum ether and DMSO (200 ml) was added and the mixture was heated to 100°C. A solution of diethyl malonate (35.2 g, 0.22mol) in DMSO (50 ml) was then added and stirred for 10 min to give a clear solution. A solution of 4-bromo-3-nitrobenzophenone (30.6 g, 0.10 mol) in DMSO (100 ml) was added and the resulting dark solution kept at 100 C for 1 h. The solution was poured into water (3 1) and extracted (2x) with ether. The extract was washed with water, dried (NajSOj and concentrated in vacuo to give an oil which crystallized. The solid was recrystallized from isopropyl alcohol to give 35.4 g (92% yield) of the product. 

In a typical example of the malonic ester synthesis 6 heptenoic acid has been pre pared from 5 bromo 1 pentene... 

H2C=CHCH2CH2CH2Br + CH2(COOCH2CH3)2 5 Bromo 1 pentene Diethyl malonate... 

Preparation of Diethyl (1-Methyl-2-Pentynyl) Malonate To a solution of 2B.6 g of sodium in 430 ml of absolute ethanol were added 200 g of diethyl malonate. About half of the alcohol was removed by distillation in vacuo, and thereafter a solution of 200 g of 2-bromo-3-hexyne in 100 ml of anhydrous ether was added slowly to the reaction mixture. 

The heat of reaction brought about refluxing during the addition of the 2-bromo-3-hexyne, and when the addition was complete the reaction mixture was heated to refluxing for a further period of 30 minutes. A sufficient amount of water was then added to the reaction mixture to dissolve the sodium bromide which had formed, and the only organic layer was separated, washed with water and dried over anhydrous magnesium sulfate. The dried organic layer was then fractionally distilled under reduced pressure, and the diethyl (1-methyl-2-pentynyl) malonate formed in the reaction was collected at about 117° to 120°C at the pressure of 2 mm of mercury. 

Amino acids can be synthesized in racemic form by several methods, including ammonolysis of an a-bromo acid, alkylation of diethyl acetamido-malonate, and reductive amination of an cv-keto acid. Alternatively, an enantio-selective synthesis of amino acids can be carried out using a chiral hydrogenation catalyst. 

Electrochemical reduction of 5-acetyl-10-bromo-5/f-dibenz[ >,/]azepine in the presence of quinoxalinc as a moderator and diethyl malonate as a proton donor, effects rapid and quantitative hydrodebromination without loss of the acetyl group.183... 

Malonic acid, amino-, diethyl ester, HYDROCHLORIDE, 40, 24 Malonic acid, bts(hydroxymethyl)-, DIETHYL ETHER, 40, 27 Malonitrile, condensation with tetra-cyanoethylene, 41, 99 2-Mercaptopyrimidine, 43, 6S hydrochloride of, 43, 68 Mercuric oxide in preparation of bromo-cyclopropane, 43, 9 Mesityl isocyanide, 41,103 5-Methallyl-l,2,3,4,5-pentachlorocyclo-pentadiene, 43, 92 Methane, dimesityl-, 43, 57 Methanesiileinyl chloride, 40, 62 Methanesulfonic acid, solvent for making peroxybenzoic acid from benzoic acid, 43, 93... 

With the A-ring unit readily available, we directed our attention to the formation of the B-ring. At first, we duplicated the five step scheme reported in Sih s strigol synthesis involving 1) esterification of the acid 14, 2) allylic bromination with N-bromo 8 ucc i n imi d e (NBS) to 15, 3) condensation with the sodium salt of dimethyl malonate to 16, 4) alkylation with methyl bromoacetate to 17, and 5) acid catalyzed hydrolysis and decarboxylation to the acid 18. 

Malonic ester syntheses, 30, 7 Malononitrile, 37, 53 Malonyl dichloride, 33, 20 Mandelic acid, 36, 3 Mandelic acid, />-bromo, 35,11 Mannich reaction, with acetone, 37,18 Mercaptoacetaldehyde, diethyl ACETAL, 35, 51... 

Potassium 4-chloro-3,5-dinitrobenzene-sulfonate, 31, 46 Potassium cyanate, 31, 9 Potassium cyanide, 30,84 32,31,63 37,47 Potassium ethyl malonate, 37, 34 Potassium ethyl xanthate, 30, 56 Potassium fluoride, 36, 40 Potassium iodide, 30, 34 31, 31, 66 Potassium metal, 37, 29, 30 Potassium methyl sulfate, 31, 73 Potassium nitrate, 31, 46 Potassium 1-nitropropylnitronate, 37, 24 Potassium oxalate, 34, 83 Potassium permanganate, 30, 87 31, 59 Potassium sulfide, 32, 103 Potassium thiobenzoate, 32, 101 Potassium thiocyanate, 32, 39, 40 Prins reaction, 33, 72 Propane, 1, 3-dibromo-2, 2-Ws-(bromo-methyl)-, 31, 82... 

Higher-molecular-weight normal 2-alkenoic acids have been prepared in poor yields by the Doebner condensation of aldehydes with malonic acid,5-7 and by the Reformatsky reaction of aldehydes with ethyl bromoacetate followed by dehydration.8 The a-iodo acid, prepared from the bromo acid, has been dehydrohalogenated with potassium hydroxide in ethanol,9 but large quantities of the a-hydroxy acid are formed as a by-product which is difficult to separate in some instances. The present procedure is an adaptation of a published method.6... 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

The tricyclic bromo THD 175 undergoes uneventfully nucleophilic substitution with aqueous dimethylamine or with sodium methoxide in methanol, under mild conditions, affording the corresponding 3-substituted THDs 173 and 130 in good yields (Equation 10) <2005JOC6230, 2005JMC2266>. Similarly, other nucleophiles such as N-(6-aminohexyl)-2-nitrobenzene sulfonamide and diethyl malonate, in the presence of triethylamine, also give substituted THDs 176 and 177, respectively, in moderate yields (Equation 10). 

Furthermore, the first catalytic synthesis of allenes with high enantiomeric purity [15c, 25] was applied recently to the pheromone 12 by Ogasawara and Hayashi [26] (Scheme 18.7). Their palladium-catalyzed SN2 -substitution process of the bromo-diene 16 with dimethyl malonate in the presence of cesium tert-butanolate and catalytic amounts of the chiral ligand (R)-Segphos furnished allene 17 with 77% ee. Subsequent transformation into the desired target molecule 12 via decarboxylation and selenoxide elimination proceeded without appreciable loss of stereochemical purity and again (cf. Scheme 18.5) led to the formation of the allenic pheromone in practically the same enantiomeric ratio as in the natural sample. 

Methyl 2-bromo-2-cyclopropylideneacetate (11a) has never been tested in these reactions, but has been used as a starting material for the stepwise construction of 1,6-heptadienes with methylenecyclopropane units for intramolecular Heck reactions. Thus, bromo ester 11a, after reduction, subsequent conversion of the resulting alcohol to the bromide and coupling with enolates of substituted malonates, was transformed into dienes of the type 254 (Scheme 73) - versatile synthetic blocks for the preparation of functionally substituted spirocyclopropanated bicyclo[4.3.0]nonenes 255a-d by a domino Heck-Diels-Alder reaction [122a]. 

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