Benzylamine, preparation

Hexamethylenetetramine. Hexa, a complex molecule with an adamantane-type stmcture, is prepared from formaldehyde and ammonia, and can be considered a latent source of formaldehyde. When used either as a catalyst or a curative, hexa contributes formaldehyde-residue-type units as well as benzylamines. Hexa [100-97-0] is an infusible powder that decomposes and sublimes above 275°C. It is highly soluble in water, up to ca 45 wt % with a small negative temperature solubiUty coefficient. The aqueous solutions are mildly alkaline at pH 8—8.5 and reasonably stable to reverse hydrolysis. 

Modification of the Erlenmeyer reaction has been developed using imines of the carbonyl compounds, obtained with aniline," benzylamine or n-butylamine. Ivanova has also shown that an A-methylketimine is an effective reagent in the Erlenmeyer azlactone synthesis. Quantitative yield of 19 is generated by treatment of 3 equivalents of 2-phenyl-5(4ff)-oxazolone (2) (freshly prepared in benzene) with 1 equivalent of iV-methyl-diphenylmethanimine (18) in benzene. Products resulting from aminolysis (20), alkali-catalyzed hydrolysis (21), and alcoholysis (22) were also described. 

The Schlittler-Muller variation of the Pomeranz-Fritsch reaction involves reaction of diethoxyethanal 17 with benzylamine 16 to prepare the desired imine 18. Intermediate 18 is subsequently cyclised to substituted isoquinoline 19. The advantage here lies in the fact that the initial condensation can still take place between an aldehyde and an amine. 

I, 4- and 3,4-Dihydroquinazolines are tautomeric but any attempts to prepare the former w ithout a 1-substituent have led to the latter. The greater stability to proto tropic change of 1,2-dihydronaphthalene over 1,4-dihydronaphthalene is also found in 3,4-dihydroquinazoline. Earlier claims to the preparation of l,4-dihydroquinazolines ° were erroneous and based on incomplete experimental data. The first 1,4-dihydroquinazoline was prepared as recently as 1961. 1-Methyl and l-benzyl-l,4-dihydroquinazolines were obtained from o-methylamino-and o-benzylamino-benzylamines (42) by formylation and ring closure. Attempts to remove the benzyl group gave 3,4-dihydroquinazoline. These 1,4-dihydro compounds are susceptible to oxidation, and attempts made to prepare 1,2-dimethyl-1,4-dihydroquinazoline from o-... 

Dihydroquinazolines are stable and a large number have been prepared. They have been synthesized by reductive cyclization of acyl derivatives of o-nitrobenzylamines, and by acylation of o-amino-benzylamines followed by ring closure. The ring closure can be effected by heating with anhydrous zinc chloride ° or by distillation. ... 

Amino-3-alkyl derivatives of474 have been prepared and found to undergo facile nucleophilic 5-substitution with methanolic hydrazine (65°, 4 hr, 75% yield), hydroxide ion (20°, 3 hr, 75% yield), or pro-panolic benzylamine (100°, 5 hr, 80% yield). The first two reactions may proceed by a ring-opening and reclosure sequence. ... 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

The procedure described is a modification of the general procedure of Angyal2 for the preparation of aldehydes from benzylamines by the Sommelet reaction. Isophthalaldehyde has been prepared from w-xylene by preparation of the tetrachloro derivative and hydrolysis,3 from isophthaloyl chloride by the Rosenmund reaction,4 from a,a -dibromo-m-xylene by the Sommelet reaction,5 and from isophthaloyl chloride by reduction with lithium tri-Cbutoxyaluminumhydride.6... 

The ureas, e.g. 28 (R = NMe2), derived from the corresponding 2-(l-arylviny )benzylamines by reaction with (dimethylamino)carbamoyl chloride (Me2NCOCl) in the presence of triethyl-amine, undergo cyclization in refluxing phosphoryl chloride to the 5-aryl-3-(dimethylamino)-l//-2-benzazepin-3-amines. e.g. 29a.84 Prepared similarly are the 3-(4-methylpiperazin-l-yl) compound 29b and the 3-methyl derivative 29c from the corresponding urea and amide, respectively. 

The beads prepared above (11.58 g.) are suspended in 175 ml. of boiling absolute ethanol, and 0.94 g. (0.0159 mole) of aqueous 85% hydrazine monohydrate is added with stirring. The resulting mixture is refluxed for 10 hours, after which the polymer is collected by filtration and washed with 150-ml. portions of ethanol, aqueous 0.2A sodium hydroxide, distilled water, and anhydrous methanol. After vacuum drying at 60° for four hours, the yield of polymeric benzylamine is 10.38 g. 

B. Polymeric Urea [Benzene, diethenyl-, polymer with ethenylbenzene, [[[[(1 methylethyl)amino]carbonyt]amino]methyl] deriv.] A 10.0-g. portion of benzylamine polymer beads prepared as in Part A and 125 ml. of tetrahydrofuran (Note 6) are combined in a 300-ml., three-necked, round-bottomed flask equipped with a magnetic stirrer, a dropping funnel, and a condenser fitted with a gas-inlet tube A nitrogen atmosphere is established in the system, and the slurry is stirred while 1.35 g. (0.0159 mole) of isopropyl isocyanate [Propane, 2-isocyanato-] is added. This causes an exothermic reaction, which subsides after about 20 minutes. The mixture is then stirred at room temperature for 22 hours and at reflux for an additional 4 hours. The beads are collected by filtration, washed with 150-ml. portions of tetrahydrofuran (Note 6) and methanol, and dried under reduced pressure over calcium chloride to yield 9.09 g, of the isopropyl urea polymer. 

The Strecker reaction has been performed on the aldehyde 182 prepared from L-cysteine [86] (Scheme 28). The imine was formed in situ by treatment with benzylamine, then TMS cyanide was added to afford prevalently in almost quantitative yield the syn-diamine 183, which is the precursor of (-l-)-biotin 184. The syn selectivity was largely affected by the solvent, toluene being the solvent of choice. Since the aldehyde 182 is chemically and configurationally unstable, a preferred protocol for the synthesis of 183 involved the prehminary formation of the water-soluble bisulfite adduct 185 and the subsequent treatment with sodium cyanide. Although in this case the syn selectivity was lower, both diastereomers could be transformed to (-l-)-biotin. 

Rather than preforming the a-amino ketimines to be reduced, it is often advantageous to form in situ the more reactive iminium ions from a-aminoketones and primary amines or ammonium salts in the presence of the reducing agent, e.g., sodium cyanoborohydride. Use of this procedure (reductive amination) with the enantiopure a-aminoketone 214 and benzylamine allowed the preparation of the syn diamines 215 with high yields and (almost) complete diastereoselectivities [100] (Scheme 32). Then, the primary diamines 216 were obtained by routine N-debenzylation. Similarly, the diamine 217 was prepared using ammonium acetate. In... 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

Aqueous aza-Diels-Alder reactions of chiral aldehydes, prepared from carbohydrates and with benzylamine hydrochloride and cyclopentadiene, were promoted by lanthanide triflates (Eq. 12.65).137 The nitrogen-containing heterocyclic products were further transformed into aza sugars, which are potential inhibitors against glycoprocessing enzymes. 

Other SC- and BSC-PEG derivatives were prepared using the same general protocol. The active carbonate contents of the products were determined according to Kalir et al. (77) by reacting aliquots of the polymers with an excess of benzylamine and back titration of the latter with perchloric acid in dioxane using thymol blue as an indicator. The results of these determinations are summarized in Table I. 

Imidazo[2,l- ][l,7]naphthyridines can be prepared by reaction of the ketonaphthyridinium salt 300 with ammonium acetate and iron(m) chloride at high temperature (Equation 102) <2001AJC105>. Reaction of the />m-fused [2,7]naphthyridine 301 with benzylamine or 2-phenylethylamine in the presence of silica gel gives a pentacyclic imidazonaphthyridine 302 (Equation 103) <2001H(54)721>. 

Lithium aluminum hydride reduction of 31 in the presence of benzylamine affords a 70% yield of l-benzylamino-2-oxaadamantane.154 This approach is patented as a general method for the preparation of N-substituted 2-oxa-adamantyl-l-amines.155 Transannular cyclization of 31 or 35 in the presence... 

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

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