Amines methylene activation

The nucleophilic attack on the nitrogen atom of a nitroso group is the limiting stage of condensation reactions of nitroso compounds with amines, methylene-active, and organomagnesium compounds, of Ehrlich-Sachs, Fischer-Hepp, Burton, and other reaction [161,162]. 

The rate of stripping or the stripabiUty on cataly2ed urethane and epoxy resin finishes can be increased by adding formic acid, acetic acid, and phenol. Sodium hydroxide, potassium hydroxide, and trisodium phosphate [10101-89-0] may be added to the formula to increase the stripabiUty on enamel and latex paints. Other activators include oleic acid [112-80-17, trichloroacetic acid [76-85-9], ammonia, triethanolamine [102-71-6], and monoethyl amine. Methylene chloride-type removers are unique in their abiUty to accept cosolvents and activators that allow the solution to be neutral, alkaline, or acidic. This abihty gready expands the number of coatings that can be removed with methylene chloride removers. 

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

The most characteristic reaction of butadiene catalyzed by palladium catalysts is the dimerization with incorporation of various nucleophiles [Eq. (11)]. The main product of this telomerization reaction is the 8-substituted 1,6-octadiene, 17. Also, 3-substituted 1,7-octadiene, 18, is formed as a minor product. So far, the following nucleophiles are known to react with butadiene to form corresponding telomers water, carboxylic acids, primary and secondary alcohols, phenols, ammonia, primary and secondary amines, enamines, active methylene compounds activated by two electron-attracting groups, and nitroalkanes. Some of these nucleophiles are known to react oxidatively with simple olefins in the presence of Pd2+ salts. Carbon monoxide and hydrosilanes also take part in the telomerization. The telomerization reactions are surveyed based on the classification by the nucleophiles. 

This chapter reports on the reactivity of organic carbonates as alkylating agents, with emphasis on the lightest term of the series, DMC. Under both CF and batch conditions, DMC can react with a number of nucleophilic substrates such as phenols, primary amines, sulfones, thiols, and methylene-active derivatives of aryl and aroxy-acetic acids. The mechanistic and synthetic aspects of these processes will be elucidated. 

The aldehyde moiety of 50 can be condensed with either amines or active methylene compounds. In the case of reactions with amines, the aldehyde 50 (presumably obtained by reduction of the cyano group with diisobutyl-aluminium hydride (DIBAL-H)) forms simple Schiff bases 51 (Equation 20) <1998J(P1)3557>. 

Other Applications. Hydroxylainine-O-sulfonic acid has many applications in the area of organic synthesis. The acid has found application in the preparation of hydrazines from amines, aliphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. 

For the quantitative deprotonation of nitroalkanes and methylene-active compounds, there is no need to employ the heavy artillery of lithium amides rather, it suffices to employ alkaline earth metal alkoxides or alkaline earth metal hydroxides. In addition, equilibrium reactions between these C,H acids and amines form enough enolate to initiate enolate reactions. 

The flash photolysis of hexaarylbiimidazole produces imidazolyl radicals " which have been shown to be more nearly planar than the parent dimers ort/io-substituents in the aryl rings decrease the radical stability. The radicals oxidize electron-rich substrates by rapid electron abstraction from tertiary amines, iodide, and metal ions, and by hydrogen abstraction from phenols, mercaptans, secondary amines, and active methylene com-pounds." " Studies have been made of the photooxidation of /euco-triphenyl-methane dyes by these radicals." " ... 

The Michael 1,4-addition of methylene activated compounds to various a,p-unsaturated carbonyl compounds in water was promoted by amines grafted on silica gel by a post-modification method. Since the reaction was carried out in a triphasic system, due to low solubility of organic substrates, internal heating by microwave irradiation (100 W) was exploited. In the model reaction between ethyl 2-oxocyclopentanecarboxylate (52) and 3-buten-2-one (53) (Scheme 3.16), the temperature was ramped for 2 min from room temperature to 80 °C. 

Primary amines anchored to silica have been utilized as catalysts for Knoevenagel condensation reactions. For example, silica gel functionalized with a propylamino moiety [SiO2-(CH2)3-NH2] was employed in the reaction of different methylene active compounds with aldehydes and ketones for the production of electron-poor olefins 73 (Scheme 3.21). ... 

An interesting comparison of the activity of primary and tertiary amino groups linked to MTS silicas in the reaction of benzaldehyde with ethyl cyanoacetate (Scheme 3.21, R = CN, R ElOCO, Ph, II) was reported. The results showed that catalysis induced by tertiary amine was relevant to classical base activation of the methylene group followed by nucleophilic attack to the carbonyl function, whereas primary amines could activate the carbonyl group by imine formation followed by Mannich-like nucleophilic attack by the activated ethyl cyanoacetate, as shown in Scheme 3.9. 

Aminofuran-, -pyrrole-, and -thiophene-3-carboxylates and -3-nitriles such as 58 are obtained in a simple, one-step reaction from a-oxo-alcohols, -amines, and -thiols (57) with methylene-active nitriles.53 Thus ethyl 2-amino-4,5,6,7-tetrahydrobenzo[h]thiophene-3-carboxylate (59) results from cyclohexanone, sulfur, and ethyl cyanoacetate26,53 (Scheme 11). The accessible... 

Sulfur dissolved in DMF thionates in the presence of sec-amines methylene groups activated by a captor group. The halogen is then replaced by the amine, the overall sequence leading to thioamides. This is shown below for bromotrifluoro-acetone (Scheme 29, refs. 23, 24). 

Diazo group transfer. The title reagent, prepared by adding imidazole to NaNs and SO2CI2 in MeCN, is shelf-stable. It is useful in transfer a diazo group to amine and active methylene compounds. 

Methylthio-4,6-diphenyl-1,3-thiazinium perchlorate (101) reacts with primary amines and active methylene compounds at C-2 to give the 2-imino (102) and the methylene derivatives (103), respectively. However, hydrazine and hydroxylamine give 3,5-phenylpyrazole (104) and 3,5-diphenyl-isoxazole (105), respectively, and it is possible that here the reactions proceed through initial nucleophilic attack at C-4 as indicated in Scheme 14 <87NKK780>. 

As stated above, Knoevenagel condensations can occur on catalysts combining acidic and basic sites. A well-known system is the combination of an amine and its carboxylic acid salt. Such catalysts seem to activate the carbonyl substrates, usually by imine or enamine formation, and the activated substrate is subsequently activated by protonation. The base assists the deprotonation of a methylene-active compound, forming a carbanion, followed by nucleophilic attack on the proto-nated imine (Scheme 3A). 

Dimethylcarbonate (DMC) is an environmentally friendly substitute for dimethylsulfate (DMS) and methyl halides in methylation reactions. It is also a very selective reagent. The reactions of DMC with methylene-active compounds produce monomethylated derivatives with a selectivity not previously observed. The batchwise monomethylation of arylacetonitriles, arylacetoesters, aroxyacetonitriles, methyl aroxyacetates, ben larylsulfones and alkylarylsulfones with DMC achieve >99% selectivity at 180-220°C in the presence of K2CO3. Mono- -methylation of primary aromatic amines at 120-150 °C in the presence of Y- and X-type zeolites, achieved selectivities up to 97%. At high temperature (200°C) and in the presence of potassium carbonate as the catalyst, DMC splits benzylic and aliphatic ketones into two methyl esters in contrast, DMC converts ketone oximes bearing a methylene group to 3-methyl-4,5-disubstituted-4-oxazolin-2-ones. Dibenzylcarbonate... 

Also of interest in the preparation of diazoalkanes are the di-azotization of primary amines with activating substituents in the a-position, reaction of hydrazine or hydrazides with dichlorocarbene, diazo-group transfer reactions, the oxidation of hydrazones, and condensation reactions of active methylene compounds. 

The Mannich Reaction involves the condensation of formaldehyde with ammonia or a primary or secondary amine and with a third compound containing a reactive methylene group these compounds are most frequently those in which the methylene group is activated by a neighbouring keto group. Thus when acetophenone is boiled in ethanolic solution with paraformaldehyde and dimethylamine hydrochloride, condensation occurs readily with the formation of... 

Knoevenagel reaction. The condensation of an aldehyde with an active methylene compound (usually malonic acid or its derivatives) in the presence of a base is generally called the Knoevenagel reaction. Knoevenagel found that condensations between aldehydes and malonic acid are effectively catalysed by ammonia and by primary and secondary amines in alcoholic solution of the organic amines piperidine was regarded as the best catalyst. 

Typical nucleophiles known to react with coordinated alkenes are water, alcohols, carboxylic acids, ammonia, amines, enamines, and active methylene compounds 11.12]. The intramolecular version is particularly useful for syntheses of various heterocyclic compounds[l 3,14]. CO and aromatics also react with alkenes. The oxidation reactions of alkenes can be classified further based on these attacking species. Under certain conditions, especially in the presence of bases, the rr-alkene complex 4 is converted into the 7r-allylic complex 5. Various stoichiometric reactions of alkenes via 7r-allylic complex 5 are treated in Section 4. 

Michael condensations are catalyzed by alkaU alkoxides, tertiary amines, and quaternary bases and salts. Active methylene compounds and aUphatic nitro compounds add to form P-substituted propionates. These addition reactions are frequendy reversible at high temperatures. Exceptions are the tertiary nitro adducts which are converted to olefins at elevated temperatures (24). 

Shown ate glycidyl methacrylate to introduce epoxide fiinctionahty, acetoacetoxyethyl methacrylate to introduce active methylene groups, dimethylaminoethyl methacrylate to introduce amine fiinctionahty, phosphoethyl methacrylate for strong acid fiinctionahty, and isocyanatoethyl methacrylate to introduce isocyanate fiinctionahty, which may then react with a wide variety of nucleophiles. 

Apparently the alkoxy radical, R O , abstracts a hydrogen from the substrate, H, and the resulting radical, R" , is oxidized by Cu " (one-electron transfer) to form a carbonium ion that reacts with the carboxylate ion, RCO - The overall process is a chain reaction in which copper ion cycles between + 1 and +2 oxidation states. Suitable substrates include olefins, alcohols, mercaptans, ethers, dienes, sulfides, amines, amides, and various active methylene compounds (44). This reaction can also be used with tert-huty peroxycarbamates to introduce carbamoyloxy groups to these substrates (243). 

MSC undergoes reactions with alcohols, amines, active methylene compounds (in the presence of bases), and aromatic hydrocarbons (in the presence of Friedel-Crafts catalysts) to replace, generally, a hydrogen atom by a methanesulfonyl group (382—401). 

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