Methylene-dialkyl

Aryl-dichlorphosphoryloxy-methylen)-dialkyl- E5, 45 (R-CO-NR2 +POCl2) Aryl-trimethyl- -iodid E16a, 1000 (N-Alkylier.)... 

In more recent work, Leandri and coworkers have solvolysed a series of methylene dialkyl and methylene spiro cyclopropyl bromides as a method for preparing a-allenic tertiary alcohols. An example is shown below in the reaction of 1. Robertson and... 

Otherwise, the main reactions at the methylene group are the dialkylation with alkyl haUdes (77), the acetylation with acetyl chloride which yields acetylma1 ononitrile [1187-11-7] (78), the Knoevenagel condensation, as well as the condensation with triethyl orthoformate, gives... 

The heavy metal salts, ia contrast to the alkah metal salts, have lower melting points and are more soluble ia organic solvents, eg, methylene chloride, chloroform, tetrahydrofiiran, and benzene. They are slightly soluble ia water, alcohol, ahphatic hydrocarbons, and ethyl ether (18). Their thermal decompositions have been extensively studied by dta and tga (thermal gravimetric analysis) methods. They decompose to the metal sulfides and gaseous products, which are primarily carbonyl sulfide and carbon disulfide ia varying ratios. In some cases, the dialkyl xanthate forms. Solvent extraction studies of a large number of elements as their xanthate salts have been reported (19). 

In the alternative approach.the 1,3-dipolar system can be constructed in several ways. Treatment of a-chloroacylhydrazones of diaryl ketones and certain aralkyl and dialkyl ketones (382) with NaH in anhydrous THF gives l-(disubstituted methylene)-3-oxo-l,2-diazetidinium inner salts (383). Reaction of (383) with DMAD in methylene chloride gave (384), a 2 1 adduct with loss of CO. Double bond migration in (384) occurred on heating to give (385). The intermediate in the cycloaddition was found to be (386), which on heating lost CO to form a new ylide system which in turn underwent reaction with more DMAD <81JA7743). 

A methylene base formed from quinaldine ethiodide, l-ethyl-2-methyl-ene-1,2-dihydroisoquinoline (129), exhibits a number of reactions characteristic of enamines (207,209). On treatment with benzoylchloride a dialkylated product (130) is produced by C and subsequent O benzoylation (210). 

In the alkylation of enolate anions, a mixture of mono- and polyalky lation produets is usually obtained, and when enolization of a di-a-methylene ketone is possible toward both sides, a mixture of di-a- and a,a -dialkylation products ean be expeeted. Thus the enamine alkylation sequenee beeomes partieularly attractive when eontrolled monoalkylation is imperative beeause of difficulties in separation of a mixture of alkylation produets. One of its first synthetie applications was in the reaetions of /8-tetralones with alkyl halides. Yields in exeess of 80% were usually found 238-243) in these reaetions, which make valuable intermediates for steroid and diterpene syntheses more aecessible. 

Trifluoroacetonitrile is activated toward reaction with active methylene groups. Cyclocondensation with dialkyl 3-oxopentanedioates and 1,3-diphenylacetone gave 2,4-dialkoxy-6-(trifluoromethyl)-3,5-pyridinedi-carboxylates (90JOC2964) and 2-(trifluoromethyl)-4(l//)-pyridinones (90JOC380), respectively. 

Olah and coworkers56 found that treatment of dialkyl, arylalkyl and diaryl sulphides with nitronium hexafluorophosphate (or tetrafluoroborate) 32 at —78° in methylene chloride resulted in the formation of sulphoxides in moderate to high yields (Table 3). In the oxidation of diphenyl sulphide which affords diphenyl sulphoxide in 95% yield, small amounts of the ring nitration products (o- and p-nitrophenyl phenyl sulphides) were formed. However, diphenyl sulphone and nitrophenyl phenyl sulphoxide were not detected among the reaction products. 

The Mannich condensation has traditionally been carried out in the presence of water as a three-component condensation involving a carbonyl compound (or related carbon nucleophile), formaldehyde, and a primary or secondary amine. The initial step is a condensation between the latter two reactants to form a mono- or dialkyl(methylene)ammonium ion which subsequently serves as the electrophilic partner in the reaction. With unsymmetrical ketones aminomethylation generally occurs at both positions to give mixtures of isomeric 3-amino ketones. The ratio of the isomers depends strongly on the structure of the ketone, and the more highly branched (3-amino ketone usually predominates. 

In recent years a number of methods have been developed for the preparation of dialkyl(methylene)ammonium salts (Mannich reagents)and their use in Mannich-type condensation reactions under anhydrous conditions has improved the scope and efficiency of this important synthetic process. However, the orientation of the Mannich reaction may nevertheless be difficult to control. Apart from the work of the submitters, the preparation of isomer-ically pure Mannich bases has only been achieved by indircci... 

Similarly with other reactive methylene groups like P diketones we get mono and dialkylated... 

The reactions of ethyl cyanoformate and dialkyl malonates in the presence of zinc chloride and triethylamine, or in the presence of TiCl4 or SnCl4 in methylene chloride at reflux temperature for 3 hr, or at room temperature overnight, gave amino(alkoxycarbonyl)methylenemalonates (314, R1 = Et) in good yields [79TL2525 81JAP(K)71050],... 

Dialkyl malonates were reacted with trichloroacetonitrile in methylene chloride in the presence of Ni(acac)2 catalyst under nitrogen at room temperature for 3 hr to give dialkyl (2,2,2-trichloro-l-aminoethylidene) malonates in 65% and 80% yields (86M15) (Scheme 29). 

When reacted with trialkyl phosphite in benzene for 1 hr, dialkyl magnates (364, X = F) gave a mixture of amino(trifluoromethyl)methylene-malonates (365) (20% yields), dialkyl trifluoromethyl(substituted amino)-methylenemalonates (366) (40-45% yields), and dialkyl chlorophosphate (-20%) (86ZOB805). The reactions of dialkyl malonates (364, X = F, Cl) and triphenylphosphine in the presence of triethylamine in diethyl ether for 1 hr gave trihalomethyl(substituted amino)methylenemalonates (367) in 87-95% yields. The treatment of a solution of dialkyl trifluoromethyl-(substituted amino)methylenemalonates (366, R1 = Et) in benzene with aqueous hydrochloric acid gave amino(trifluoromethyl)methylene-malonates (368) in 82-84% yields (86ZOB805) (Scheme 32). 

Alkylidene phenylaminomethylenemalonates (444) were reacted with sodium hydride or lithium hydride in acetonitrile at 40°C for 2 hr. The reaction mixtures were then cooled to 0-20°C, and they were treated with a solution of dialkyl peroxydicarbonate in methylene chloride for 24 hr to give 5-alkoxycarbonyloxy-5-phenyliminomethyl-1,3-dioxane-4,6-diones (1616) in 54-75% yields (80CB2630). 

Dialkyl and isopropylidene malonates were reacted with 2-chloro-l,3-thiazinium chlorides (1686) in methylene chloride in the presence of triethylamine to give (1,3-thiazin-2-ylidene)malonates (1687) in 5-13% yields (89AP593, 89GEP3803783). 

Whereas alkylation of activated methylene systems by classical methods produces a mixture of mono- and dialkylated products, with the latter frequently predominating, phase-transfer catalytic procedures permit better control and it is possible to obtain only the monoalkylated derivatives. Extended reaction times or more vigorous conditions with an excess of the alkylating agent lead to dialkylated products or, with dihaloalkanes, carbocyclic compounds as the technique mimics dilute concentration conditions, e.g. the resonance stabilized cyclopentadienyl anion, generated under solidiliquid two-phase conditions, or under liquiddiquid conditions, reacts with 1,2-dihaloethanes to form spiro[2,4]hepta-4,6-diene (70-85%) [1-3]. Reaction with dichloromethane produces bis(cyclopenta-2,4-dien-l-yl)methane (60%) [4],... 

The low acidity of methylene groups, which are activated by only one electron-withdrawing mesomeric substituent, generally results in a lower reactivity under phase-transfer catalytic conditions. Monoalkylation normally occurs, sometimes to the complete exclusion of dialkylation, and further alkylation is generally only... 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

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