Formamides reduction

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

When quinoxaline or its derivatives are treated with formic acid in formamide, reductive formylation proceeds and l,2,3,4-tetrahydroquinoxaline-l,4-dicarbaldehydes are formed." ... 

The tetrahedral intermediate 7 formed by quenching the aryllithium 6 with dimethylformamide was directly analogous to the one formed by treating the aldehyde 8 with diethyl amine to form 12 (Scheme 8). This led us to consider the option of trapping the aryllithium 6 with di /A[y/formamide. Reduction would then provide the desired benzylic amine 13 without proceeding through... 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

Eig. 7. CycHc voltammograms for the reduction of 1.0 mAf [2,2 -ethylene-bis(nitrilomethyHdyne)diphenolato]nickel(II) in dimethyl formamide at a glassy carbon electrode, in A, the absence, and B and C the presence of 2.0 and 5.0 mAf 6-iodo-l-phenyl-l-hexyne, respectively (14). 

Greater stereoselectivity for the formation of equatorial amines has been found in the reduction of enamines with formic acid or formamides (553-559). The selective formation of 3-a-amino-5- -steroids by this method and of 3- 3-amino-5- 3-steroids by catalytic reduction (5<50) of the corresponding enamines is of interest. 

The Batcho-Leimgruber indole synthesis involves the condensation of o-nitrotoluene derivatives 1 with formamide acetals 2, followed by reduction of the trans-p-dimethylamino-2-nitrostyrene 3 which results to furnish indole derivatives represented by... 

Good yields of pyrido[2,3-d]pyrimidiries (37) were also oblaiiied by the action of formamide on o-amino nitriles (36). Reduction of 2-amino-4,6-dimethylnicotinitrilc yields the 3-aminomcthyl compound (38). Acylation to the 3-aoylaminomethyl derivative (39), followed by cyolization, by means of heat or phosphoryl chloride, yielded the dihydropyrido[2,3-d]pyrimidines (40). ... 

In a departure from the prototype molecule, the benzylpiperi-done is first converted to the corresponding aminonitrile (a derivative closely akin to a cyanohydrin) by treatment with aniline hydrochloride and potassium cyanide (126). Acid hydrolysis of the nitrile affords the corresponding amide (127). Treatment with formamide followed by reduction affords the spiro oxazinone... 

Table 7 reveals that the grafting of TAC onto PE decreases the equilibrium contact angles of water and formamide from 92° to 65° and from 75° to 53°, respectively. This decrease is a function of the monomer level and the irradiation dose. At a fixed irradiation dose of 15 Mrad, variation of the TAC level from 0.5 to 3 parts causes a reduction in the contact angles of water by 13° (from 88° to 75°) and of formamide by 11° (from 72° to 61°). This is due to the fact that the concentration of... 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Nitration of 3,4-dimethoxypropiophenone (91) affords the nitro derivative 92, and catalytic reduction leads to the aminoketone (93). This is then converted to the corresponding formamide by means of formic-acetic anhydride. Treatment with ammonia Completes Construction of the quinazoline ring. 

This type of charge reduction by charge transfer to the solvent molecule occurs in general when SI are polar solvent molecules of aprotic character such as dimethyl-sulfoxide, dimethyl formamide, and acetonitrile. Protic solvents such as water lead to charge reduction which involves an intracluster proton transfer reaction ... 

Ye et al. reported that the reduction of 2,4-dichlorophenyl-2-chloroethanone 1 with potassium borohydride in dimethylformamide to give 90% a-chloromethyl-2,4-dichlorobenzyl alcohol 2. Alkylation of imidazole with compound 2 in dimethyl formamide in the presence of sodium hydroxide and triethylbenzyl ammonium chloride, gave l-(2,4-dichlorophenyl-2-imidazolyl)ethanol 3 and etherification of 3 with 2,4-dichlorobenzyl chloride under the same condition, 62% yield of miconazole [9]. 

Multiple products are possible from C02 hydrogenation, but all of the products are entropically disfavored compared to C02 and H2 (Scheme 17.1). As a result, the reactions must be driven by enthalpy, which explains why formic acid is usually prepared in the presence of a base or another reagent with which formic acid has an exothermic reaction. Of the many reduction products that are theoretically possible, including formic acid, formates, formamides, oxalic acid, methanol, CO, and methane, only formic acid and its derivatives are readily prepared by homogeneous catalysis. 

Three alternative mechanisms have been mentioned in the literature. Reduction of C02 to CO followed by carbonylation of dimethylamine was ruled out by Haynes et al. [3] for RhCl(PPh3)3 because no carbonyl complexes were detected. Aminolysis of formate complexes (Eq. (14)) was proposed by Kudo et al. [69], but strong evidence has not been obtained. Finally, C02 is known to react with the amine to produce a carbamate salt (Eq. (15)), and it is possible that the pathway to the formamide is by hydrogenation of the carbamate rather than of the C02. 

The reductive cyclopropanation with in situ generated titanacyclopropanes can also be applied to alkyldiformylamines 58, which are easily prepared from inexpensive formamide (57). Both formyl groups are converted to cyclopropyl groups, and the alkyldicyclopropyl-... 

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