Diphenyl morpholine

Hydroxy-4-benzyl-5,6-diphenyl-2,3-dihydro-1,4-oxazin wird durch Lithiumalanat iiber das Enol-Salz zu 2-Hyclroxy-4-benzyl-2,3-diphenyl-morpholin reduziert6. Durch Ringoffnung und Schliefiung wird die Hydr-oxy-Gruppe verschoben. 

C) Preparation of Doxapram Hydrochloride [3,3-Diphenyl-1-Ethyl-4-(2-Morpholino-Ethylj-2-Pyrrolidinone Hydrochloride Monohydrate] A solution of 25 grams (0.076 mol) of 4-(2-chloroethyl)-3,3-diphenyl-1-ethyl-2-pyrrolidinone and 13.3 grams (0.153 mol) of morpholine in 500 ml of absolute ethanol was heated at 95°-120°C for 21 hours in a closed system and concentrated in vacuo. The residue was dissolved in 3(X) ml of two normal hydrochloric acid and extracted with 150 ml of ethyl acetate. A solid crystallized (13 g) during the extraction and was removed by filtration. MP 217°-219°C. The acid extracts were made basic with sodium hydroxide and extracted with ether, and the ether solution was concentrated in vacuo and the residue was suspended in six normal hydrochloric acid. Additional crystalline product formed and was recrystallized from two normal hydrochloric acid. Yield, 10 grams MP 217°-219°C. Total yield, 23 grams (70%). 

The thermolysis of 4-azidophenyl methyl ketone in morpholine at 170°C yields a mixture of the expected 5-acetyl-2-morpholino-3f/-azepine (33) and 6-acetyl-2-morpholino-3//-azepine (34), the product of a unique and totally unexpected thermal rearrangement of the 5-acetyl derivative.119 Similar results can be obtained in hot piperidine, whereas thermolysis of 4-azido-diphenyl ketone under similar conditions yields only the 6-benzoyl-2-(cycloalkylamino)-3//-azepines (7-18%) accompanied by much tar. 

Acyl nitroso compounds react with 1, 3-dienes as N-O heterodienophiles to produce cycloadducts, which have found use in the total synthesis of a number of nitrogen-containing natural products [21]. The cycloadducts of acyl nitroso compounds and 9,10-dimethylanthracene (4, Scheme 7.3) undergo thermal decomposition through retro-Diels-Alder reactions to produce acyl nitroso compounds under non-oxidative conditions and at relatively mild temperatures (40-100°C) [11-14]. Decomposition of these compounds provides a particularly clean method for the formation of acyl nitroso compounds. Photolysis or thermolysis of 3, 5-diphenyl-l, 2, 4-oxadiazole-4-oxide (5) generates the aromatic acyl nitroso compound (6) and ben-zonitrile (Scheme 7.3) [22, 23]. Other reactions that generate acyl nitroso compounds include the treatment of 5 with a nitrile oxide [24], the addition of N-methyl morpholine N-oxide to nitrile oxides and the decomposition of N, O-diacylated or alkylated N-hydroxyarylsulfonamides [25-29]. 

Fenclofenac Fenclofenac, o-[2,4-dichlorophenoxy)phenyl]acetic acid (3.2.45), is synthesized from 2,4-dichlorophenol and 2-chloroacetophenone, the reaction of which in the presence of sodinm hydroxide and powdered copper forms the corresponding 2-acetyl-2, 4 -dichloro-diphenyl ester (3.2.43). The resulting product is reacted with sulfur and morpholine according to Willgerodt method, giving thioamide (3.2.44), which is further hydrolyzed to the desired fenclofenac [109,110]. 

In a subsequent paper (87), the same authors investigated the palladium-catalyzed allylic aminations with pyrphos-functionlized PPI and PAMAM dendrimers as multidentate ligands. Zero to four generation PPI-(pyrphosPdCl2)x and PAMAM-(pyrphosPdCl2)x neutral dendrimers (97) showed a strong positive dendritic effect on the selectivity of the allylic amination of 1,3-diphenyl-1-acetoxypropene with morpholine (at 45°C in DMSO). 

Diphenyl tellurium bis[trifluoroacetate] reacted under the same conditions with tetrame-thylurea, sulfoxides, triphenylphosphane oxide and sulfide, triphenylarsane oxide, pyridine 1-oxides, tetramethylpiperidine, benzimidazole, morpholine, and 7V,Ar-diphenylthiourea to give 1 1 complexes as sharp-melting, colorless solids that are soluble in common organic solvents3. 

The adduct 32 of diphenylcyclopropenethione to the morpholine enamine of acetophenone reacts with dimethyl acetylenedicarboxylate to yield a mixture of 1,2-diphenyl cyclopropene and dimethyl 4-morpholino-3-phenylthiophene-1,2-dicarboxylate (equation 21)41. 

Preparation of ethyl 2-(2,2-diphenyl-ethylimino)-5-[4-(4-carboxy)-piperidine-l-sulfonyl]-phenyl -morpholin-4-yl-methanone... 

Although bradykinin receptor binding testing data were not supplied by the author, 2-(2,2-diphenyl-ethylamino)-5-[4-(4-isopropylpiperazine-l-carbonyl)-piperidine-l-sulfonyl]-phenyl -morpholin-4-yl-methanone, (la), and 2-(2,2-diphenyl-ethylamino)-5- [4-(4-methylpiperazine-1 -carbonyl)-piperidine-1 -sulfonyl] -phenyl -morph olin-4-yl-methanone, (lb), were especially preferred. 

Alternate Name t-butyl 6-oxo-2,3-diphenyl-4-morpholine-carboxylate. 

R,5R,6S)-4-tert-Butoxycarbonyl-5,6-diphenyl-3-(r-prop-2 -enyl)morpholin-2-one 4-Morpholinecarboxylic acid, 2-oxo-5,6-diphenyl-3-(2-propenyl)-, 1,1-dimethylethyl ester, 3R-... 

Dihydroxy-6.7-diphenyl- pteiidine Morpholine 2-Morpholinocaxbonyl-3-morpholinocarbonylamino-5,6-diphenyl and 2-amino-3-morpholinocarbonyl-5,6-diphenyl 451... 

Normal nucleophilic substitution occurred on treatment of 2-carbamoyl-3-chloropyrazine with alcoholic methylamine at 130° (423, 836) 2-chloro-3-(4 -morpholinocarbonyOpyrazine with morpholine at reflux in benzene (867) 2dimethyl sulfoxide at 65° (857) and cyclohexylamine in benzene at reflux (946) 3-chloro-2-methoxycarbonyl-5-phenylpyrazine with alcoholic methylamine at 140° (375) 2-carboxy-3-chloropyrazine with anhydrous ammonia at 100° for 5 hours (947) 2-carbamoyl-6-chloropyrazine with aqueous methylamine at reflux (940) 2-chloro-6-(4 -morpholinocarbonyl)pyrazine (and other amides) and 2-chloro-6-methoxycarbonylpyrazine with morpholine (and other amines) (870, 948, 949) and 2-chloro-6-methoxycarbonylpyrazine with liquid ammonia at 80° (870). 2-Chloro-3-methoxycarbonylpyrazine fused with guanidine carbonate gave 2-amino4-hydroxypteridine and its 7-methyl-, 7-phenyl, and 6,7-diphenyl analogues were prepared similarly (371,375). 

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