Aminobenzaldehyde

Merck s reagent grade of sodium sulfide nonahydrate was used. Since sodium sulfide decomposes on contact with air, a freshly opened bottle should be employed. Sodium Sulfhy-drate (Hooker Electrochemical Company hydrated sodium hydrosulfide) is also satisfactory the amount should be based upon the formula NaHS 2H20, and an equivalent amount of sodium hydroxide in excess of the 27 g. is required. 

The /i-nitrotoluene used was Eastman Kodak Company practical grade. 

The steam distillation should be carried out as rapidly as possible. The distillate contains ethanol, / -toluidine, and some unchanged / -nitrotoluene. 

It is sometimes necessary to suspend the precipitate in about 200 ml. of ice water, stir it vigorously, and filter again to remove all traces of alkali. 

The chief impurities are the polymeric condensation products of / -aminobenzaldehyde with itself. No satisfactory method for recrystallization has been found. If the melting point is high and a pure product is desired, it is best to extract with boiling water until the filtrate is clear, and extract the monomer from the water with ether. This procedure gives recoveries of 25-30%. 

Checked by Cliee S. Hamilton, C. W. Winter, and Harry M. Walker. 

three-necked flask is employed as a reaction vessel from which the product can be steam-distilled immediately after completion of the reaction (Note 1). It is convenient to arrange the apparatus for the reaction and that for the steam distillation on the same steam bath, with provision for the rapid connection of the flask to the distillation assembly at the desired time. For use as a reaction vessel the flask is mounted on a steam bath and fitted with a mechanical stirrer and a reflux condenser the third neck is closed by a cork. - 

In the steam-distillation assembly (Note 1) one of the small necks of the flask is fitted with a steam-inlet tube, connected through a water trap to a steam line the other small neck is closed by a cork. The central neck is fitted to a Kjeldahl trap leading to a 50-cm. Allihn condenser set downward and connected in series to a 50-cm. Liebig condenser. The second condenser leads to a SOO-ml. three-necked flask used as the receiver. The receiving flask is immersed in an ice bath and fitted with an Allihn reflux condenser. 

When all the apparatus has been set up and tested the flask is connected to the reaction assembly, and 175 ml. of water, 105 g. (0.38 mole) of ferrous sulfate heptahydrate, 0.5 ml. of concentrated hydrochloric acid, and 6 g. (0.04 mole) of o-nitrobenzalde-hyde are introduced in the order given. The stirrer is then started, and the flask is heated by means of the steam bath. When the temperature of the mixture reaches 90°, 25 ml. of con- 

Immediately after the addition of the last portion of ammonium hydroxide, the reflux condenser and stirrer are removed and the flask is connected to the steam-distillation assembly. The mixture is steam-distilled as rapidly as possible, and two 2S0-ml. fractions of distillate are collected during a period of 10-13 minutes (Note 2). The first fraction is saturated with sodium chloride, and the solution is stirred at 5° until precipitation appears complete. The solid is collected on a Buchner fimnel and dried in the air. The product weighs 2.72-3.11 g. (57-65%) and melts at 38-39°. The second fraction of the distillate is saturated with sodium chloride and combined with the filtrate remaining from the first fraction. The combined solution is extracted with two 45-ml. portions of ether. The combined ether extract is filtered, dried over anhydrous sodium sulfate, and concentrated by distillation, finally under reduced pressure. The residue solidifies on cooling and weighs 0.6-1.0 g. it can be purified by steam distillation from 40-50 ml. of saturated sodium chloride solution until 100 ml. of distillate is collected, saturation of the distillate with sodium chloride, cooling, and filtration. The pure product so obtained weighs 0.42-0.87 g. The total yield (Note 3) is 3.3-3.6 g. (69-75%). 

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The alkaloid vasicine was first isolated from Adhatoda vasica in 1925 but the structure (996) was elucidated only after a great amount of work, culminating in two independent syntheses in 1935 (B-53MI21301). It was made subsequently by a simple route from 2-aminobenzaldehyde and 4-amino-2-hydroxybutyraldehyde (994) followed by dehydration of the tricyclic intermediate (995) (60TL(25)44>. Vasicine has bronchodilatory activity of a low order. Two related unnamed alkaloids (997) and (998) were obtained in 1965 from members of the Araliaceae family, viz. Mackinlaya subulata and M. macrosciadia both had been synthesized earlier (66AJC151). 

Aminobenzaldehyde phenylhydrazone (Nitrin) [63363-93-9] M 211.3, rn 227-229 . Crystd from acetone. [Kndpfer Monatsh Chem 31 97 1910.]... 

Friedlander reported the condensation of 2-aminobenzaldehyde (4) with acetaldehyde (5) to provide quinoline (6) in 1882. ... 

Depending upon the structure of the substrates 49, 52, and 56 hexahydropyrido[l,2-n]-[3,l]benzoxazines 50, 54, 2-aminobenzaldehyde 53, 1-substituted piperidones 51, 55, 57, 3,4,5,6-tetrahydropyridinium salt 58, or their mixture was obtained during the oxidation of 1-(2-hydroxymethyl-, 2-formyl- and 2-acetylphenyl)piperazines (49, 52, 56) with Hg(II)-EDTA complex (Schemes 6-8) (79AP219, 98ZN(B)37, 98ZN(B)1369). 

Aminoquinazolines can be prepared by the reaction of guanidine with 2-aminobenzaldehydes, although yields are only moderate, as shown by the synthesis of 2-amino-5-bromoquinazoline 841 which occurred in only an 18% yield <2003JA2084>. 

Aminobenzaldehyde [529-23-7] M 121.1, m 39-40°. Distd in steam and crystd from water or EtOH/ether. 

The sulfinamide anhydrides (473) underwent regiospecific cyclization with isoquinolines (474) yielding 475 [76JA6186 79JAP(K)79135799]. 2-Aminobenzaldehydes also condensed with 3,4-dihydroisoquinoline pic-... 

The published work on the synthesis of this system involved the reaction of anthranilic acid with a reactive pyrimidine derivative. Thus, 4-chloropyrimidines (520) condense with 2-aminobenzaldehyde (47JCS726) or an anthranilic acid derivative [66T(S)227 68ZC103 89MI2] to give the pyrimido-[6,1 -b]quinazolines (521). 

Polyaza rings suffer complete hydrolytic ring cleavage. Monocyclic 1,2,3-triazines are hydrolyzed by acid to yield 1,3-dicarbonyl compounds (Scheme 15). 1,2,3-Benzotriazines are easily converted into derivatives of 2-aminobenzaldehyde. 1,2,4,5-Tetrazines (180) are hydrolyzed with a base to give aldehyde hydrazones, RCH = NNHCOR. 

Diamine oxidase (DAO) activity could be determined by first reacting cadaverine with an enzyme to produce A1-piperidine, which then was reacted with 2-aminobenzaldehyde and finally chromium(VI) oxide to form 6,7,8,9-tetrahydro-ll//-pyrido[2,l-b]quinazolin-ll-one (7). The latter was determined on an HPLC apparatus (Scheme 5) (84MI4). 

The course of the Friedlander condensation between 2-aminobenzaldehyde and the pyrrolidin-3-one (121) depends upon the conditions. In base the pyrrolo[3,2-6]quinoline... 

Benzotriazine, and especially its conjugate acid, reacts very easily with nucleophiles such as water or acetic acid to give derivatives of 2-aminobenzaldehyde (75JCS(P1)31,71CC828). 4-Alkyl- or 4-aryl-substituted 1,2,3-benzotriazines are more stable towards attack of water or acids. 2-Aminobenzophenone (100%) is obtained when 4-phenyl-1,2,3-benzotriazine is heated under reflux for 10 min in 10% aqueous ethanol containing concentrated sulfuric acid (75JCS(Pl)3l>. 

The self-condensation of 2-aminobenzaldehyde in the presence of suitable metal ions to form the cyclic tetramer (1), and sometimes the trimer (2), is the best-known example of this reaction type (Scheme 2). The cyclization of the / -amino ketone complex (5) provides an aliphatic example... 

Complexes of nickel(II), copper(II), cobalt(III), zinc(II), iron(II), palladium(II), platj-num(II) and vanadyl can be obtained. Although the reaction sequence is fairly general for metal ions, it is not easily extendable to substituted 2-aminobenzaldehydes. However, 2-amino-5-me-thylbenzaldehyde has recently been used successfully in the macrocyclization reaction.147... 

Aminobenzaldehyde structural fragments have been incorporated into diatninodialdehydes, which can act as precursors for macrocyclic complexes. The initial work in this area involved template reactions between dialdehydes and diamines in the presence of hydrated metal(II) acetates in methanol (equation 26).153-155 Benzene-1,2-diamines could also be used in these syntheses. 

The ligands NiV -bis-(2-aminoacetophenone)ettiylenediamine, NN -bis-(2-amino-benzophenone)ethylenediamine, and AiV -bis-(2-aminobenzaldehyde)ethylene-diamine (LH2) form mononuclear (CoLX) complexes and the more unusual bi- and tri-metallic derivatives (56) and (57).342... 

Regarding the main products corresponding to the opening of the pyridine moiety of quinoline, 2-aminobenzaldehyde and, to a lesser extent, its A -formyl derivative were formed by photocatalysis, whereas only traces of this latter product were detected when the photo-Fenton process was employed. Also, (2-formyl)phenyliminoethanol was detected only in the case of the degradation over Ti02. 

Authentic N-analogs of spirobenzopyrans, the 1,2-dihydrospiro-2//-quinolines (79) (or their open forms), have never been isolated, despite many attempts during the past 35 years. In reactions with Fischer s base, 5-nitro-2-aminosalicylaldehyde gave no reaction, whereas 2-aminobenzaldehyde gave only a polymer.7 The open form of the desired compound could be considered a quinone monoimine and therefore be expected to have poor stability. 

As early as 1986, both Wall and coworkers [46] and a Chinese group [47] recognized the potentiality of a Friedlander synthesis approach from 2-aminobenzaldehyde with the synthon 14 and developed an approach to racemic 14, based on the extremely efficient condensation of ethyl acetoacetate with cyanacetamide by Henecka [48], which provides in one step a pyridone intermediate IS with three different sub-... 

The anhydrotrimer of 2-aminobenzaldehyde, formed from the monomer on standing, or more quickly by the action of dilute acid,15 has proved to have structure 5a.13,16 The anhydro tetramer (5b)13,16 is obtained when the monomer is dissolved in 5 N hydrochloric acid and the precipitated red anhydro tetramer dihydrochloride,15 for which structure 6 has been proposed,13 is made basic with aqueous pyridine. At low concentrations (e.g., 10-5 M), equilibrium favors depolymerization to the monomer, but at higher concentrations (e.g., 10-2 M), 5a and 6 are formed in proportions depending on the strength of acid. The reaction mechanism for the formation of these oligomers has been discussed.13 The trimer (5a) and the tetramer (5b) consist of three tightly bound tetrahydroquinazoline rings and 6 has a macrocyclic structure. It is... 

When 2-aminobenzaldehyde was heated in absolute ethanol in the presence of nickel nitrate, the tridentate and tetradentate macrocyclic complexes (7 and 8, respectively) were isolated.17 The presence of copper(II) nitrate produced only the latter (8).17 Although the monomer has two functional groups and the oligomers have reactive azomethine groups, the formation of macrocyclic ligands stabilized by a metal halts further polymerization. 

From 2-Aminophenyl Ketones or 2-Aminobenzaldehydes and Urea, Carbamates, or Guanidine... 

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