Amines primary, dimethylation

Charge-transfer complexes with pyrimidine and purine bases as well as with solvents like hexa-methylphosphoramide and dimethyl sulfoxide are reported in Ref 66. The action of aromatic amines (primary, secondary, or tertiary) resulted in fume-offs or unidentifiable tars, in all cases purple or red colors developed prior to more violent reactions (Ref 66)... 

An even more convincing argument is provided by the studies (46), results of which are also shown in Fig. 14. Tri-n-butyl amine in dimethyl formamide induces only a slow polymerisation of L-proline NCA whereas the polymerisation of y-ethyl-L-glutamate NCA is very fast under these conditions even if the concentration of the base is reduced by a factor of ten (78, 46). This is a striking observation since proline NCA is an extremely reactive monomer and polymerises very fast on addition of a primary amine. However, addition of 3-methyl hydantoin,... 

The preparation of highly functionalized cyclopentadiene derivatives may by achieved by using oxalenes or their pyrylium salts (90 and 92, respectively), (see Scheme 14, where X = O). In this way, azalenes 26,51 29,8Z 88 32,51 or 3651 can be obtained by heating salts (90) with primary amines in dimethyl-formamide (Eq. 6). The reaction with sodium hydrogen sulfide gives thialenes... 

Scheme 6.7 Synthesis of carbamates from aliphatic primary amines and dimethyl carbonate (DMC) in the presence of C02. The catalytic role of C02.

Reductive amination with formaldehyde and sodium cyanoborohydride provides a convenient method for methylation of a secondary amine (or dimethylation of a primary amine). An alternative procedure uses formaldehyde together with formic acid (HCOOH) as the source of hydride in what is termed the Eschweiler-Clark reaction. Deprotonation of formic acid provides the formate anion, which delivers hydride to the iminium ion with concomitant formation of carbon dioxide. 

Methylalkylammonium salts, obtained by alkylation of primary amines with dimethyl H-phosphonate, are thermally unstable and easily yield the corresponding alkylammonium salts [292,295,296]. 

Methylation of 64 with ethereal diazomethane afforded the methyl ester 65, which was then reduced with amalgamated zinc and hydrochloric acid to give the amine 66. Methylation of the primary amine with dimethyl sulfate in the presence of potassium carbonate afforded a mixture of the monomethylamine 67 and the (hmethylamine 68, which were separated. Alkaline hydrolysis of 67 in methanol and subsequent column chromatognq>hy on Ambo lite IRA-120 completed the total synthesis of ( )-chanoclavine I acid (69). 

Ordonez et al. have developed a practical and efficient strategy to obtain N-substituted dimethyl 3-oxoisoindolin-l-yl phosphonates (241) in a one-pot reaction of 2-formylbenzoic acid, primary amines and dimethyl phosphite. This reaction proceeded in a short time either with conventional heating or microwave irradiation, under catalyst-free conditions, in good yield (69-82%) (Scheme 85). ... 

Dimethyl Sulphate Method for hydroxy compounds and for primary and secondary amines, acid amides, etc. The substance is dissolved or suspended in water, a small excess (above the theoretical) of sodium hydroxide added and then the theoretical quantity of dimethyl sulphate, the mixture being finally shaken without external warming. Methylation is usually rapid, the dimethyl sulphate being converted to methyl hydrogen sulphate... 

The Formaldehyde-Formic Acid Method, This method applies to primary and secondary amines, which when boiled with a formalin-formic acid mixture undergo complete methylation to the corresponding tertiary amine. This method has the advantage over the dimethyl sulphate method in that quaternary salts clearly cannot be formed. 

Fuactioaalizatioa is completed by aminating the chloromethylated copolymer with either primary or secoadary amines. Dimethyl amine [124 0-3] (6) is geaerally preferred, especially ia the syathesis of the macroporous anion exchangers. 

Lithium Acetylide. Lithium acetyhde—ethylenediamine complex [50475-76-8], LiCM7H -112X01120112X112, is obtained as colodess-to-light-tan, free-flowing crystals from the reaction of /V-lithoethylenediamine and acetylene in an appropriate solvent (131). The complex decomposes slowly above 40°O to lithium carbide and ethylenediamine. Lithium acetyhde—ethylenediamine is very soluble in primary amines, ethylenediamine, and dimethyl sulfoxide. It is slightly soluble in ether, THF, and secondary and tertiary amines, and is insoluble in hydrocarbons. 

Linear alpha-olefins are the source of the largest volume of ahphatic amine oxides. The olefin reacts with hydrogen bromide in the presence of peroxide catalyst, to yield primary alkyl bromide, which then reacts with dimethylamine to yield the corresponding alkyl dimethyl amine. Fatty alcohols and fatty acids are also used to produce amine oxides (Fig. 1). 

AHphatic amine oxides such as alkyl dimethyl amine oxides and aLkylbis(2-hydroxylethyl)amiae oxides range from practically nontoxic to slightly toxic (79). Reported LD qS range from 1.77 g/kg to 6.50 g/kg. The commercial concentrated products are primary skin and eye irritants. At concentrations of 2%, these products may be considered as nonirritating to the skin or eye. 

Alkyl dimethyl and dialkylmethyl tertiary amines are commercially available. These amines are prepared by reductive methylation of primary and secondary amines using formaldehyde and nickel catalysts (1,3,47,48). The asymmetrical tertiary amines are used as reactive intermediates for preparing many commercial products. 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Substituted methyl- or dimethyl amines are prepared by treating the appropriate primary or secondary amine with formaldehyde in the presence of hydrogenation catalysts (22,23). 

For primary aromatic amines dimethyl carbonate, Y-Zeolite, 130-150°, 72-93% yields. ... 

Heating a primary amine with dibenzylformamide-dimethyl acetal in CH3CN gives the formamidine in 49-99% yield. It is cleaved by hydrogenolysis (Pd(OH)2, MeOH, H2O, H2, 52-99% yield). ... 

Some substituents such as the acylamino group are readily decomposed by many nucleophiles to give a poorer leaving group (e.g., amino). Others, such as nitroamino and sulfonylamino, are less reactive when they are anionized by the nucleophile. 3-Nitroamino-pyridazine (117) and its 6-methyl derivative are readily aminated with benzylamine (130°, short time ). 4,6-Dimethyl- and 6-methyl-2-nitroaminopyrimidine undergo 2-substitution on warming a few minutes with hydroxylamine, hydrazine, primary or secondary alkylamines, or anilines. 

The deoxygeneration of nitroarenes by trivalent phosphorus compounds in the presence of amines is a useful route to 3/f-azepin-2-amines (cf. compounds 32, Section 3.1.1.4.2.2.). Subsequently, it has been shown, by carrying out the reaction in strongly basic solution, that the process can be extended to the synthesis of 1H-. 3H- and 5//-2-benzazepines from nitronaph-thalenes 43 For example, 1-nitronaphthalenes 3 with dimethyl phosphite in the presence of sodium methoxide and a primary or secondary aliphatic amine, yield the dimethyl 5//-2-ben-zazepin-3-yl phosphonates 4 accompanied, in some cases, by the isomeric 3//-2-bcnzazepin-3-yl phosphonates 5. 

Bis(bromomethyl)-5//-dibenz[/), / ]azepines, e.g. 12, prepared by free-radical bromination of the 10,11-dimethyl compound with yV-bromosuccinimide, on treatment with a primary alkyl-amine followed by alkaline hydrolysis, yield l,2,3,8-tetrahydrodibenzo[. /]pyrrolo[3,4-<7]-azepines, e.g. 13, which possess useful pharmacological properties.91,163... 

AG° was calculated for eleven amines, ranging from 2,4-dinitroaniline (AG° = + 50 kJ mol-1) to aniline ( — 41), 4-morpholinoaniline ( — 99), and 4-dimethyl-aminoaniline ( — 108). The results demonstrate clearly that a primary electron transfer is very likely, at least for those aniline derivatives with a strong electron donor in the 4-position. 

All classes of primary amine (including primary, secondary, and tertiary alkyl as well as aryl) are oxidized to nitro compounds in high yields with dimethyl dioxirane." Other reagents that oxidize various types of primary amines to nitro compounds are dry ozone, various peroxyacids," MeRe03/H202,"" Oxone ," ° tcrt-butyl hydroperoxide in the presence of certain molybdenum and vanadium compounds, and sodium perborate." ... 

Addihon of primary and secondary amines to 1,3-butadiene and isoprene at 0 to 180°C over solid bases such as MgO, CaO, SrO, LajOj, Th02, and ZrOj has also been studied. CaO exhibits the highest achvity, while ZrOj is inachve. MejNH is the most reactive amine, giving primarily the 1,4-addihon product which undergoes iso-merizahon to the enamine N,N-dimethyl-l-butenylamine. It has been proposed that addihon of amines to 1,3-dienes on basic catalysts proceeds via aminoallyl carban-ion intermediates which result from addihon of amide ions to the dienes [169, 170]. 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

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