Aminobenzyl Alcohol

Reaction of 2-aminobenzyl alcohol with butenesulfonyl chloride gave 700 which upon treatment with BuLi followed by COCI2 gave the benzoxazine 701. Thermolysis of 701 in 1,2,4-trifluorobenzene gave the thiazoloquinoline 702 (96JCS(P1)1809) via an intramolecular Diels-Alder reaction (Scheme 121). 

Furthermore, the N-alkylation of 2-aminobenzyl alcohol 114 with ketones 115 in the presence of [IrCl(cod)]2 and KOH gave quinoline derivatives 116 (Equation 10.28) [52]. The reaction may be initiated by the formation of ketimine from 114 and 115, and the ketimine thus formed is oxidized by Ir catalyst and the 114 which serves as a hydrogen acceptor giving the corresponding aldehyde, which is eventually converted into quinoline 116 through intramolecular aldol-type condensation. 

The reaction of 2-aminobenzyl alcohol 376 with 2-chloro-4,5-dihydroimidazole afforded [2-(4,5-dihydro-177-imidazol-2-ylideneamino)phenyl]methanol hydrochloride 377, which upon treatment with carbon disulfide gave l-(477-3,l-benzoxazin-2-yl)imidazolidine-2-thione 378 (Scheme 71). The assumed reaction mechanism involved the initial formation of the dithiocarbamate 379, which underwent intramolecular nucleophilic addition to furnish the unstable thiazetidine 380. By nucleophilic attack of the hydroxy group on the carbon atom of the thiazetidine ring, thiocarbamate derivative 381 was formed, which gave the final 3,1-benzoxazine 378 by an intramolecular cyclocondensation with the evolution of H2S <2006H(68)687>. 

Quinolines can be prepared from the oxidative coupling and cyclation of the 2-aminobenzyl alcohol and ketones (Scheme 4) catalyzed by the system [RhCl(PPh3)3]/KOH [58]. The reactions were carried out in dioxane at 80 °C with 85% yield in 24 h (alcohol/Rh = 100/1). However, better yields are obtained with the related ruthenium system [RuCl2(=CHPh)(PCy3)2 [59]. 

In this case, the 2-aminobenzyl alcohol is oxidized to 2-aminobenz-aldehyde, which undergoes an aldol condensation with the ketone to give an 0, /3-unsaturated ketone. This is followed by cyclodehydratisation to form quinoline. An excess of ketone is necessary to act as a sacrificial hydrogen acceptor. 

Reaction of N-(2-aminobenzoyl)-2-aminobenzyl alcohol (711JC647) or anthraniloyl anthranilic acids (597) (76JIC382) with carbon disulfide gave the 3-(2-carboxyphenyl)-2-mercaptoquinazolin-4-ones (598), which underwent cyclodehydration to the title compounds 599 (76JIC382). 

Aminobenzyl alcohols (298) give 4,4-dialkyl-4//-3,1 -benzoxazine derivatives (299) on treatment with acetic anhydride (1883CB2576). 

Such compounds are unstable unless the double bond is held in conjugation with other systems as, for example, when it is part of an aryl ring. Indeed, dihydro-3,1-benzoxazines are readily accessible from 2-aminobenzyl alcohols by condensation with aldehydes or ketones (Scheme 84) (75AP622). Oxacephems (199) also contain the 3,6-dihydro-2//-l,3-oxazine unit and they are formed for instance, on cyclization of chlorolactams (198) by the action of stannic chloride (B-80MI22701). 

A one-pot quinoline synthesis starting with 2-aminobenzyl alcohol and a,/3-unsaturated ketones using ruthenium-grafted hydrotalcites as a heterogeneous catalyst has been reported (Scheme 64) <2004TL6029>. Molecular oxygen was used for the oxidation of ruthenium and the styryl quinoline 42 was produced in good yield. The use of other donors, for example, octanal and phenylacetonitrile, yielded 3-amylquinoline and 2-amino-3-phenylquinoline, respectively. 

Reaction of 2-aminobenzyl alcohol 483 with 2-chloronicotinoyl chloride 484 in the presence of Et3N yielded the 2-hydroxymethylphenylamide-2 -chloronicotinic acid 485 (32%). Such an intermediate underwent a base promoted to give the pyridobenzo[3/][l,5]oxazocin-6-one 486 in 36% yield (Scheme 97) <1997FA751>. 

A successful ruthenium-catalyzed oxidative coupling and subsequent cyclization between 2-aminobenzyl alcohol and secondary alcohols in the presence of KOH and 1-dodecene leading to quinolines has been reported <03T7997>. After optimization of conditions, yields were fair to good. The reaction is widely applicable to a large series of 2-substituted quinolines. 

Cyanamino-4//-3,l-benzoxazine (239) can be derived from its tautomer l,4-dihydro-3,l-benzoxazine-2-cyanimine (238) by treatment with ammonia, or primary or secondary alkylamines. The starting material is synthesized by treating 2-aminobenzyl alcohol with diphenyl cyano-carbonimidate (Scheme 66) <89T829>. 

The condensation of trialkyl borates and boronic acids with 2-thio- and 2-aminobenzyl alcohols... 

Aminobenzyl alcohol and aqueous cyanic acid gave 2-ureidobenzyl alcohol, which, when briefly heated with dilute acid, gave 3,4-dihydroquin-azolin-2-one. Similarly, 2-aminobenzyl alcohol and ally isothiocyanate produced, in two steps, 3-allyl-3,4-dihydroquinazoline-2-thione (no yields given).75 2-Aminobenzhydrol (80) and aqueous thiocyanic acid, when briefly heated on a water bath, gave 4-phenyl-3,4-dihydroquinazoline-2-... 

Aminobenzoic acid has been reduced to 2-aminobenzyl alcohol by BASF, salicylic acid to salicylaldehyde in India, and oxalic acid to glyoxyllic acid in Japan and the U.K. 

Ru-grafted hydrotalcite is an excellent multifunctional catalyst for a one-pot s3mthesis of quinolines from 2-aminobenzyl alcohol 169 and various carbonyl compounds through aerobic oxidation by Ru, followed by an aldol reaction on basic sites of the hydrotalcite (Table 3) (04TL6029). 

Recently, Phan et al. (2013) prepared an open metal site MOF Cu(BDC) and successfully applied it to the modified Friedlander reaction. In the presence of 3-5 mol% Cu(BDC), several 2-aryl quinolines were efficiently synthesized from 2-aminobenzyl alcohol and methyl ketones (Scheme 4.42). Different from the previous reports, the reaction of p-methoxyacetophenone or p-nitroacetophenone did not occur in this catalytic system. 

C.S. Cho, B.T. Kim, H.-J. Choi, T.-J. Kim, S.C. Shim, Ruthenium-catalyzed oxidative coupling and cydizationbetween 2-aminobenzyl alcohol and secondary alcohols leading to quinolines. Tetrahedron 59 (2003) 7997-8002. 

Aminobenzyl alcohol could be oxidatively cyclized with ketones catalyzed by a CUCI2 catalyst with a KOH base in dioxane at 100 C under O2 atmosphere to afford quinolines in good yields. When aldehydes were used as the substrates, the desired quinolines also could be obtained in two steps under the similar conditions. Intramolecular aldol-type condensation and cyclodehydration to form quinolone are involved for this transformation [153] (Scheme 8.83). 

Scheme 8.83 Synthesis of quinolines from 2-aminobenzyl alcohol with ketones.

The chiral auxiliary sugar can be isolated by pentane extraction of the crude hydrolysis reaction mixture. The amino acids can then be purified by ion exchange chromatography. The shortcoming of this methodology is that simple amino acids such as phenylalanine are difficult to separate from the hydrolyzed by-product 2-aminobenzyl alcohol (155). According to Linderman and coworkers, the size of the... 

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