Amines benzaldehydes with

An assay method for benzaldehyde involves condensing benzaldehyde with hydroxyl amine hydrochloride to form an oxime. The released hydrochloric acid is then titrated. 

One problem with reductive amination as a method of amine synthesis is that by-products are sometimes obtained. For example, reductive amination of benzaldehyde with methylamine leads to a mixture of iV-methylbenzylamine and i -methyldibenzylarnine. How do you suppose the tertiary amine byproduct is formed Propose a mechanism. 

Condensation of 2-cyanomethyl benzaldehydes with amines carried out in the presence of a catalytic amount of trifluoroacetic acid affords 3-aininoisoquinolines (e.g.,70) <95T(51)12439>. 

The first example of this type of transformation was reported in 1974 [76]. Three catalysts were investigated, namely [Co2(CO)8], [Co(CO)g/PBu ], and [Rh6(CO)i6]. The [Co OJg/PBu ] catalyst showed activity for reductive animation using ammonia and aromatic amines. The [Rh6(CO)16] catalyst could be used for reductive animation using the more basic aliphatic amines that were found to poison the cobalt catalyst. This early report pointed out that the successful reductive animation of iso-butanal (Me2CCHO) with piperidine involves selective enamine hydrogenation, that reductive animation of cyclohexanone with isopropylamine probably involves imine hydrogenation, and that reductive amination of benzaldehyde with piperidine would presumably involve the reduction of a carbinolamine. 

An important contribution was recently made by Inoue and co-workers (35) (eq. [4]). Using the chiral cyclic dipeptide cyclo(L-Phe-L-His) these authors obtained a better than 90% e.e. in the reaction of benzaldehyde with cyanide ion. The preparation of the enantiomeric unnatural dipeptide obviously poses far fewer problems than the synthesis of an enantiomeric enzyme. It appears that, at least in principle, optically pure cyanohydrins of the desired configuration are accessible via catalysis by chiral amines or amides. 

Chiral terf-diamines complexed with LAH gave very low optical yields in reductions of prochiral ketones. A/,/V,A/, /V -Tetramethyl-l,2-cyclohexanedi-amine complexed with LAH or LiAlD4 reduced phenyl alkyl, dialkyl ketones or benzaldehyde in <15% optical yields (109). 

For example, hydrogenation of benzaldehyde with 1 mol of ammonia gave 89.4% of primary and 7.1% of secondary amine while the reaction with 0.5 mol of ammonia afforded 11.8% of the primary and 80.8% of the secondary amine [956]. 

The domino sequence leading to the conversion of 30 to 31 was performed without isolation of the intermediates. The sequence is thought to proceed as shown in Scheme 7.6. Treatment of 30 with benzaldehyde with azeotropic removal of water led to the protection of the amine as the benzaldehyde imine 33, which was directly mesylated to give 34. The solution of 34 was treated with allylamine (4 equiv.) and autoclaved at 112°C for 15 h to provide 31 in 80% yield after acidic hydrolysis. It is assumed that the benzaldehyde imine of 33 is exchanged with allyl amine to form the aminomesylate 35, which undergoes fast ring closure to the aziridine 36. Then allylamine adds to the... 

The chiral dipolarophiles of Garners and Dogan, which were derived from Oppolzer s sultam, have been previously discussed in Section 3.2.1 and, in an extension to these results, the sultam moiety was used as the stereodirecting unit in enantiopure azomethine ylides (56). The ylides were generated either by thermo-lytic opening of N-substituted aziridines or by the condensation of the amine functionality with benzaldehyde followed by tautomerism. These precursors were derived from the known (+)-A-propenoylbornane-2,10-sultam. Subsequent trapping of the ylides with A-phenylmaleimide furnished the cycloaddition products shown in Schemes 3.60 and 3.61. 

Formation of aldehydes. Aldehydes can be prepared by the carbonylation of halides in the presence of various hydride sources. The carbonylation of aryl and alkenyl iodides and bromides with CO and H (1 1) in aprotic solvents in the presence of tertiary amines affords aldehydes[373,374]. Aryl chlorides, as tricarbonylchromium derivatives, are converted into aldehydes at 130 C[366], Sodium formate can be used as a hydride source to afford aldehydes. Chlorobenzene (514) was carbonylated at 150 °C to give benzaldehyde with CO and sodium formate by using dippp as a ligand[375,376]. 

One of the first so-called potassium sparing, nonthiazide diuretic agents contains a pterdine nucleus. This is reflected in the use of the pterdine staring material tetra-aminopyrimidine (38-2) in the synthesis. Thus, reaction of benzaldehyde with that polyamine and potassium cyanide leads to the formation of the cyanohydrinlike a-aminonitrile (63-2) from reaction of the most basic amino group. Treatment of the intermediate with a base leads to the addition of the amine to the nitrile to give the dihydropteridine (63-3). Simple exposure to air leads to dehydrogenation and the formation of triamterine (63-4) [65]. 

Reductive amination of benzaldehyde with (R)-81 provided the corresponding benzyl amine, which was reductively alkylated with formaldehyde to give 82 (Scheme H) " Compound 82 was debenzylated by hydrogenation in the presence of Pearlman s catalyst to afford frovatriptan ((/J)-6). Alternatively, monomethylation of amine (/ )-81 was affected by treatment with carbon disulfide and dicyclohexylcarbodiimide in pyridine to provide isothiocyanate 83, which was reduced with sodium borohydride to give (l )-6. 

In an attempt to couple halobenzaldehydes with amines, A1203 was pre-absorbed with the substituted benzaldehydes and imidazole or piperidine as a base and irradiated with microwaves. However, the corresponding benzylic alcohols and benzoic acids were unexpectedly obtained by the Cannizzaro route (Scheme 4.20). The products of Cannizzaro reactions were also obtained as the main products, when microwave-assisted condensation reactions of benzaldehydes with vinyl acetate using barium hydroxide as the catalyst were attempted40. 

The phenethylamine homologue of TMA-6 is well known, but is virtually unexplored pharmacologically. The above benzaldehyde with nitromethane in glacial acetic acid containing ammonium acetate gave the appropriate beta-nitrostyrene as yellow crystals with a mp 177-177.5 °C. This, with LAH in ether, gave 2,4,6-trimethoxyphenethylamine (2,4,6-TMPEA, or 2C-TMA-6) as the picrate salt (mp 204-205 °C) or the hydrochloride salt (mp 234-235 °C). It has been shown not to be a substrate to the soluble amine oxidase from rabbit liver, a property it shares with mescaline, but whether it is or is not active in man is at present unknown. 

Several reports describe additives for example, tertiary amine bases, weak acids, and strong acids have been examined, with limited effect, except for the strong acids, which stop the reaction completely.101 C2-symmetric chiral diols substantially improve proline-catalysed ee, conversion efficiency, and yield in the reaction of acetone with benzaldehyde, with addition of (S )-BINOL giving further improvement.102... 

The amines 3 reported by Morao and Cossio also constitute neutral dendritic catalysts without metal sites they consist of a simple amine core functionalised with Frechet dendrons (Fig. 6.44) [74]. Such amines can catalyse the nitroaldol or Henry reaction [75] between aromatic aldehydes and nitroalkanes. Whereas neither the yield nor the stereoselectivity (syn/anti 1 1) of the reaction of p-nitro-benzaldehyde with nitroethane was found to change on use of different generations of dendritic catalysts, a distinctly negative dendritic effect was observed in the reaction of benzaldehyde with 3-nitro-l-propanol. Catalysts 3 a and 3 b gave... 

A wide variety of methods have been described for the synthesis of variously substituted phenethylamines. Some frequently used procedures are presented in Scheme 1. Most of these have been discussed in previous reviews (305, 306). Condensation of an appropriately substituted benzaldehyde with nitromethane followed by reduction of the nitrostyrene (Method A) has proved to be a versatile method which has been employed by numerous workers (cf. 306, 358). Another common method (Method B) affords the amines by reduction of substituted phenylacetonitriles obtained via benzylchlorides (cf.. 306) or benzylamines (307). Reduction of phenylacetamides with lithium aluminum hydride (Method C) has also been applied successfully (308, 309). The substituted phenylacetamides were obtained either via diazoketones by an Amdt-Eistert synthesis (308) or by transformation of the corresponding acetophenones (310). 

Compound (408), which was prepared by the condensation of the amine (407) with benzaldehyde in the presence of piperidine, upon treatment with phenylhydrazine afforded the orange pyrazolo[3,4-6]pyridin-2-one (410) (69%) (Scheme 45) <9iPS(63)ll9>. The structure (410) was confirmed by an alternative synthesis involving a reversal of the reactants. In this case compound (407) was initially reacted with phenylhydrazine to give compound (409) and subsequent condensation with benzaldehyde gave the product (410). 

Imines are formed when any primary amine reacts with an aldehyde or a ketone under appropriate conditions for example, cvclohexylamine and benzaldehyde. 

Emerson and Waters alkylated primary aromatic amines with C2-C7 aliphatic aldehydes and benzaldehyde over Raney Ni in the presence of sodium acetate as a condensing agent and obtained /V-alkylanilincs in 47-65% yields.33 With C2-C5 aldehydes, up to 10% of the tertiary amines were produced, but no tertiary amines were found in the case of heptanal and benzaldehyde. With acetaldehyde in the absence of sodium acetate, aniline was recovered unchanged over platinum oxide and a mixture of amines resulted over Raney Ni, compared to 41 and 58% yields of N-ethylaniline over platinum oxide and Raney Ni (eq. 6.12), respectively, in the presence of sodium acetate. 

CsX is useful for the simple Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate even a simple NaY is sufficiently basic to form carbamates starting from primary aromatic amines and dialkyl carbonates (35, 36). At contrast CsjO-MCM-41 can also be used for the addition of C02 to epoxides, or for Michael addition of one or two molecules of diethyl malonate on neopentylglycol diacrylate (37, 38) ... 

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