Bromomalonates diethyl

Pyrrolidine-2-thione is /S-alkylated with bromomalonic diethyl ester. On treatment with a solution of KHCO3, the resulting iminium salt 1 yields a thiirane 2 which desulfurizes at 60°C to give 3 [14]. 

Reaction of aniline derivatives with 4-chlorobutyroyl chloride followed by cyclization with sodium ethoxide and subsequent thionation promoted by sonication gave the corresponding A -arylpyrrolidine-2-thiones 126. Zinc-mediated condensation of diethyl bromomalonate with 126 using iodine as activator gave the vinylogous urethanes 127 whose cyclization with PPA gave the tricyclic compound 128 which upon hydrolysis afforded the acid 129 (96TL9403). 

The hydrazinolysis is usually conducted in refluxing ethanol, and is a fast process in many cases. Functional groups, that would be affected under hydrolytic conditions, may be stable under hydrazinolysis conditions. The primary amine is often obtained in high yield. The Gabriel synthesis is for example recommended for the synthesis of isotopically labeled amines and amino acids. a-Amino acids 9 can be prepared by the Gabriel route, if a halomalonic ester—e.g. diethyl bromomalonate 7—is employed as the starting material instead of the alkyl halide ... 

The radical alkylation of ketones is achieved by their conversion into the desired N-silyloxy enamines 81 (Scheme 13). The reaction of 81 with diethyl bromomalonate in the presence of EtsB (0.5 equiv) in benzene was performed in open air and stirred at room temperature for 3h. With nitro compounds it is achieved by their conversion into the desired ]V-bis(silyloxy)enamines (82) (Scheme 13). When the reaction is carried out with 82 and alkyl iodides with an electron-withdrawing substituent at the a-position, using V-70 as radical initiator (2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile)), it underwent a clean radical alkylation reaction to yield an oxime ether. Successful radical alkylation of... 

Bromides are less reactive than the corresponding iodides in atom transfer processes. However, activated bromides such as diethyl bromomalonate [36] and bromomalonitrile [53] react with olefins under Et3B/02 initiation. Kha-rasch type reactions of bromotrichloromethane with alkenes are also initiated by Et3B/02 [41]. On the other hand, a remarkable Lewis acid effect was reported by Porter. Atom-transfer reactions of an a-bromooxazolidinone amide with alkenes are strongly favored in the presence of Lewis acids such as Sc(0Tf)3 or Yb(0Tf)3, this reaction was successively applied to the... 

The reaction of tetrahydro-l,3-thiazine-2-thione and diethyl 2-chloro-malonate in the presence of triethylamine in boiling methylene chloride for 1.5 hr gave tetrahydro-1,3-thiazin-2-ylidenemalonate (508) in 33% yield via 507 through Eschenmoser sulfur elimination, together with traces of the mesoionic derivative (509) [77JCS(P 1) 1107]. In a similar reaction, diethyl 2-bromomalonate afforded the mesoionic compound (509) in 80% yield. Tetrahydro-l,3-thiazin-2-ylidenemalonate (508) was also obtained in 42% yield from 509 by irradiation in the presence of tributylphosphine in ethanol for 15 hr under argon [77JCS(P1)1107]. 

The reaction of the sodium salt of imidazo[l,5-J][l,2,4]triazinethione (512) and diethyl 2-bromomalonate in dimethylformamide at room temperature overnight gave (imidazotriazinylidene)malonate (513) in 14% yield (85JMC1704). 

Dihydrothieno[2,3-/]-l,4-thiazepin-5(2//)-thione (514) was reacted with diethyl 2-bromomalonate in methylene chloride under argon for 2.5 hr. The reaction mixture was then treated with a 10% aqueous solution of potassium hydrogen carbonate for 30 min to give (thienothiazepinylide-ne)malonate (515) (86EUP183994). 

The reaction of diethyl bromomalonate with a 3 1 mixture of pyrroli-dinethiones (516 and 517) in the presence of sodium ethoxide gave a 3 1 mixture of isomeric (2- and 5-pyrrolidinylidene)malonates (518 and 519) in 73% yield (89H435). 

Attempts to convert 1-bromo-l-phenylacetonitrile into the dicyano derivative under liquidrliquid two-phase conditions have been unsuccessful but, on addition of aqueous sodium hydroxide, l,2-dicyano-l,2-diphenylethene is formed by an oxidative dimerization mechanism [18], Similarly, diethyl bromomalonate fails to produce the corresponding azide with lithium azide under catalytic conditions the sole product (15%) is the ethene-l,l,2,2-tetracarboxylate [19]. 

More recent reports from Cordova [155] and Wang [156] have described the cyclopropanation of a, P-unsaturated aldehydes 99 with diethyl bromomalonates 100 and 2-bromo ethyl acetoacetate catalysed by a series of diaryIprolinol derivatives. Both describe 30 as being the most efficient catalyst in many cases and optimal reaction conditions are similar. Some representative examples of this cyclopropanation are shown in Scheme 40. The transformation results in the formation of two new C-C bonds, a new quaternary carbon centre and a densely functionalised product ripe for further synthetic manipulation. Triethylamine or 2,6-lutidine are required as a stoichiometric additive in order to remove the HBr produced during the reaction sequence. The use of sodium acetate (4.0 equivalents) as an additive led to subsequent stereoselective ring opening of the cyclopropane to give a,P-unsaturated aldehydes 101. It can be envisioned that these highly functionalised materials may prove useful substrates in a variety of imin-ium ion or metal catalysed transformations. 

In contrast, when the reaction was conducted using diethyl malonate instead of bromomalonate in the presence of Na2C03 under the HSVM conditions, there was obtained not the cyclopropanated product but a C o derivative having two bis(ethoxycarbonyl)methyl groups at the 1,4-positions 46 in 18% yield (82% based on consumed Cgo) (Scheme 21) [52]. Previously it was reported that... 

Cyclopropanation of Cjq with diethyl bromomalonate in toluene with NaH as auxiliary base proceeds smoothly at room temperature (Scheme 3.5). By-products are unreacted Cjq and higher adducts. The formahon of higher adducts is discussed in detail in Chapter 10. The monoadduct can be isolated easily from the reach on mixture by column chromatography. Saponificahon of such di(efhoxycarbonyl)-methylene adducts of Cgg is achieved by treatment with NaH in toluene at elevated temperatures and subsequent quenching with methanol (Scheme 3.6) [32], This method provides easy access to defined water-soluble fullerenes and can also be applied to higher adducts. These malonic acid derivatives of are very soluble in polar solvents, for example acetone, THF or basic water, but insoluble in aqueous acids. 

Recently, a solvent-free variation was found to be equally effective. The inorganic base Na2C03 was utilized to replace the organic base DBU in a mechanochemical reaction under high-speed vibration milling conditions [37]. The yields with diethyl bromomalonate are in the range 40-50%. 

One modification of the Bingel reaction involves DBU as a base. Initial experiments showed that exposure of CgQpjg to DBU leads to a complete loss of fluorine [71]. Fortunately this defluorination does not take place in the presence of diethyl bromomalonate. Reaction of CgQpjg with DBU and diethylbromomalonate in toluene at room temperature yields three products and unreacted CgQpjg [67, 71]. The three products are the result of mono-, bis- and tris-substitution their relative yield depends on how fast the base is added. The reaction does not - as in the usual Bingel reaction - proceed via a nucleophilic addition reaction to one double bond but as a nucleophilic substitution with a Sj.j2 -mechanism. The bromomalonate anion attacks a double bond in 5-position to one of the least sterically hindered fluorine atoms, which leads to the loss of this fluorine. The bromine atom is not replaced (Scheme 9.6). 

Scheme 10.13 Topochemically controlled solid-state synthesis of bisadduct 61 and subsequent cyclopropanation to give [2 4]-hexakisadduct 62. (i) 180°C, 10 min (ii) 40 equiv. diethyl bromomalonate, 40 equiv. DBU.

The first example of a tether remote functionalization was the synthesis of the tris-64 (Scheme 10.14) [75,78]. For this purpose the computer-aided chemically designed addend 63 was allowed to undergo a successive nucleophilic cyclopropanation/ [4-1-2] cycloaddition sequence yielding the tris-adduct 64 in 60% yield with complete regio selectivity. Subsequent cyclopropanation of the remaining octahedral sites with a large excess of diethyl bromomalonate and DBU afforded the hexakisadduct 65... 

Scheme 10.14 Tether-mediated synthesis of trisadduct 64 and subsequent transformation into the [1 2 3]-hexakisadduct 65. (i) DBU, toluene, room temp. 12 h, reflux 16 h (ii) 10 equiv. diethyl bromomalonate, 10 equiv. DBU.

The manner in which a carbene was generated was found to be critical to the product distribution in a synthesis of 4(5//)-thiooxazolones (Scheme 6.9). Treatment of diethyl bromomalonate with excess triethylamine in the presence of benzoyl isothiocyanate afforded a mixture of the 4(5//)-thiooxazolone 25 (44%) and the 1,3-oxathiole 26 (minor). However, if the carbene was generated via copper-catalyzed decomposition of diethyl diazomalonate, then 26 was isolated as the major product, albeit in low yield (22%). 

One of the first examples of addition of a zinc enolate to an alkyne was a report dealing with the zinc or cadmium stearate-catalyzed addition of substituted malonates to acetylene under pressure250. Later, Schultze described the intermolecular nucleophilic addition of the zinc enolate derived from diethyl bromomalonate to phenylacetylene in refluxing xylene leading to the alkylidene malonate 392 (equation 171)251. 

The synthesis of the 4,5,6,7-tetrahydrotetrazolo[l,5-a]pyrimidine ring started by reacting 5-aminotetrazole with diethyl bromomalonate to afford diethyl(tetrazol-5-ylamino)malonate (633), whose chloroacetylation led to the formation of 634 rather than 636. Treatment with triethylamine induced ring closure of the chloroacetyl derivative to afford the tetrazolo[l,5-ajpyrimidine 635 rather than the isomer 637 (93ACH683) (Scheme 128). 

Reaction of N-substituted bromomethanesulfonamides with 2 equiv of potassium carbonate and an cr-haloketone, ester, or nitrile leads directly to the /3-sultams 187 substituted at the C-3 position by an EWG. This base-promoted condensation can be used with a-halo ketones, esters, and nitriles where a second Sn2 intramolecular displacement can operate in tandem fashion (Scheme 60). This domino alkylation sequence exhibits a reactivity order where ketone > nitrile > ester (Table 14). The process is particularly efficient when diethyl bromomalonate or 3-chloro-2-butanone are involved <2004CJC113>. 

During the synthesis of the isocoumarin moiety of heliquinomycin, diethyl bromomalonate and phthalaldehydic acid 1137 condense to form the dihydroisocoumarin 1138 in excellent yield (Equation 442) <2000TL29>. 

Scheme 1.21 Schematic representation of the cyclopropanation of SWCNTs and the introduction of chemical markers for AFM visualization and 19F NMR spectroscopy and XPS (i) diethyl bromomalonate, DBU, room...

A 1.10-mg amount of purified SWCNT materia] was annealed under vacuum (10-3 mbar) at 1000 °C for 3 h prior to use. To a suspension of this material in dry ODCB, 1.8 mmol of diethyl bromomalonate and 3.3 mmol of DBU were added. The mixture was allowed to react for 2 h under stirring. The modified SWCNTs were isolated from the reaction mixture by filtration and washed thoroughly with ODCB followed by ethanol [160]. 

Photolysis of diethyl bromomalonate in benzene in the presence of compounds with a benzylic hydrogen as possible H-atom source leads to reduction of the ester and bromina-tion of the benzylic compound263. The malonyl radical and not the Br atom turns out to be the H-atom abstracting agent. 

A third amino acid synthesis begins with diethyl a-bromomalonate. First the Br is replaced by a protected amino group using the Gabriel synthesis (see Section 10.6). Then the side chain of the amino acid is added by an alkylation reaction that resembles the malonic ester synthesis (see Section 20.4). Hydrolysis of the ester and amide bonds followed by decarboxylation of the diacid produces the amino acid. An example that shows the use of this method to prepare aspartic acid is shown in the following sequence ... 

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