AMINO-1-CYMENE

Aminobenzyl alcohol, 21,10 a-AMINOBENZYL CYANIDE, 22, 23, 25 2-Amino- -cymene, 22, 9 < -AMINODIETHYLACETIC ACID, 22, 13 a-AMINO-a-ETHYLBUTYRIC ACID, 22, 13 2-Aminoheptane, 23, 70 (Z/-0-AMINOHYDROCINNAMIC ACID, 22, 26 a-AMINOISOVALERIC ACID, 20, 106... 

Catalytic hydrogenation is performed in alcohol solution over Raney nickel at 25° to 100° and 30 atm. or over platinum oxide at room temperature and 1 to 2 atm. The reaction is highly expthermic therefore, precautions should be taken against excessive reaction temperatures. Typical illustrations are found in the preparations of 2-amino- -cymene (90%) and 3,4-diethylaniline (90%). Heterocyclic nitro compounds in the quinoline and dibenzothiophene series also respond favorably to catalytic hydrogenation. 

P-Cynniduie Carvaaylamne, 2-amino- cymene, 2 amiTio-1 -mei l-i-iaopropylbemene, 2 meBtyl taopropylamline)... 

After the electrolytic action. has continued for a suitable period, the contents of the vessel are allowed to cool, following which the unchanged nitro-cymene is separated for re-use, and the l-methyl-2-amino-4-iso-propyl-5-hydroxy benzol is filtered off from the remaining acid solution, whidh latter is strengthened for re-use. The l-methyl-2-amino-4-isopropyl-5-hydroxy benzol is then diazotised, and further reduced in an alkaline solution of stannous chloride, in the usual and well-known manner, with the resulting- production of thymol (l-methyl-4-isopropyl-5-hydroxy benzol). 

Cyclic imines 8 and 9 are intermediates or models of biologically active compounds and can be reduced with ee-values of 88 to 96% using Ti-ebthi, Ir-bcpm or Ir-binap in the presence of additives (entries 5.7, 5.9), as well as with the transfer hydrogenation catalyst Ru-dpenTs (entries 5.8, 5.10-5.12). As pointed out earlier, Ru-diphosphine-diamine complexes are also effective for imines, and the best results for 7 and 8a were 88% and 79% ee, respectively [36]. Azirines 10 are unusual substrates which could be transfer-hydrogenated with a catalyst prepared in situ from [RuCl2(p-cymene)]2 and amino alcohol L12, with ee-values of 44 to 78% and respectable TOFs of up to 3000 (entry 5.13). 

Sinou and coworkers evaluated a range of enantiopure amino alcohols derived from tartaric acid for the ATH reduction of prochiral ketones. Various (2R,iR)-i-amino- and (alkylamino)-l,4-bis(benzyloxy)butan-2-ol were obtained from readily available (-I-)-diethyl tartrate. These enantiopure amino alcohols have been used with Ru(p-cymene)Cl2 or Ir(l) precursors as ligands in the hydrogen transfer reduction of various aryl alkyl ketones ee-values of up to 80% have been obtained using the ruthenium complex [93]. Using (2R,3R)-3-amino-l,4-bis(benzyloxy)butan-2-ol and (2R,3R)-3-(benzylamino)-l,4-bis(benzyloxy)butan-2-ol with [lr(cod)Cl]2 as precursor, the ATH of acetophenone resulted in a maximum yield of 72%, 30% ee, 3h, 25 °C in PrOH/KOH with the former, and 88% yield, 28% ee, 120 h with the latter. 

Bisquaternary, as well as monoquaternary compounds and various amino derivatives, react with tetraphenylborate and similar compounds to form stable ion-pair complexes. TPSB was found to be very suitable as an ion-pairing agent for bisquaternary drugs with which it forms very insoluble compounds. The TPSB complexes were prepared in situ, by soaking the TPSB (potassium salt)/PVC membranes in the appropriate bisquaternary solution. Of the plasticizers tested, 2-nitrophenyloctyl ether (NPOE), dioctylphthalate, di-iso-butylphthalate, nitrobenzene, 2-nitro- -cymene, NPOE showed the best behavior in terms of response time and reproducibility. The membrane compositions were 3.2% (w/w) TPSB, 64.5% (w/w) NPOE and 32.3% (w/w) PVC. 

Nitro-p cymene, col ndls (from dil alc),mp 5(15°, bp 133.5° at 20mm pressure, Qvapzn 1290 kcal/ mol was obtd in addn to other products by nitrat-ing p-cymol, or by diazo-tizing either 3-nitro-2-amino-I-methyl 4-isopropylbenzene or the 5-nitro deriv in coned H2S04 or in glac AcOH coned H2S04 and boiling the diazonium salt soln with ale (Ref 4)... 

Another potential approach towards 1 was reported by Seido et al. utilizing an asymmetric reduction of the ketone (57 Scheme 15) as the key step. Acylation of the lithium enolate of methyl phenylacetate with the imidazolide, obtained by treatment of the acid 56 with A, V -carbonyldiimidazole, gave the ketoester 57 in 66.4% yield. Asymmetric reduction of 57 with [RuI(/7-cymene)(5)-binap]I, tin chloride, and cam-phor-lO-sulfonic acid in methanol at 80 °C afforded the alcohol 58 as a mixture of syn and anti forms in 87.4% yield. The ratio of syn to anti isomers was 76.3 23.7 and the enantiomeric purity of each form was 95.6% ee and 97.8% ee, respectively. Tosylation of 58 with p-toluenesulfonyl chloride and pyridine in the presence of catalytic amounts of DMAP yielded a diastereomeric mixture of tosylate 59 in 61.8% yield. Deprotection of the /V-Cbz group in 59 by hydrogenation over 5% Pd-C followed by cyclization of the resulting amino tosylate 60 with potassium carbonate in methanol furnished methylphenidate as a mixture of erythro and threo isomers in a 7 3 ratio and 77.5% yield. 

KOH, z-PrOH, chiral ferrocenyl amino alcohol cat [RuCl(p-cymene)]2... 

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