Oxidation Of Tertiary Amines Research Articles

Studies on tertiary amine oxides. LXIV. Reaction of 4-nitroquinoline 1-oxide and related compounds with potassium cyanide.

Treatment of 4-nitroquinoline 1-oxide (1) with potassium cyanate in hot ethanol afforded 4-ethoxyquinoline 1-oxide. On the other hand when potassium cyanide was applied instead of the cyanate, the reaction followed an alternate course giving 3-cyano-4-quinolinol (3). Compound 3 was produced also from reactions in 90% ethanol, DMF, DMSO and dioxane, the best yield being obtained from the reactions in DMF at 80-90°. It was further disclosed that besides 1, 2-chloro-(13), 2-bromo-4-nitroquinoline 1-oxides (14), 4-nitroquinoline (18) and 2-bromo-4-nitroquinoline (19) underwent the same type of reaction.

Liquid-liquid extraction of isothiocyanic acid by high-molecular-weight extractants

Data on the extraction of isothiocyanic acid, and the co-extraction of water, by several high-molecular-weight extractants, viz. three amines, a substituted quaternary ammonium salt, a tertiary amine oxide, a tertiary phosphine oxide and a phosphate ester are reported. The extraction constants decrease in the order Primene > Amberlite > Alamine ≫ TOPO > TBP. As for AlamO, evidence is presented that 2AlamO·HNCS is formed besides the normal adduct AlamO·HNCS. With all the extractants, except the phosphate ester, the isothiocyanate adducts have a nearly pure ion-pair structure.The majority of the extractants easily take up isothiocyanic acid in excess of the stoichiometric amount. The extraction constants decreas in the order Aliquat>Alamine>AlamO>Amberlite>TOPO>Primene>TBP.

Studies on tertiary amine oxides. LXII. A novel formation of quinolinium methylides by the reaction of quinoline 1-oxides with active methylene compounds in the presence of an acylating agent.

The reaction of quinoline 1-oxide with ethyl cyanoacetate and acetic anhydride in dimethylformamide (DMF) or dimethylsulfoxide (DMSO) at low temperatures was found to give quinolinium-ethoxycarbonylcyanomethylide as the main product besides the normal 2-substituted and 4-substituted products. This novel formation of N-ylide was examined under various conditions, and the following features were revealed. Acetic anhydride was most effective as acylating agent, and DMF and DMSO seemed most suitable media for the N-ylide formation. In addition to ethyl cyanoacetate, malonodinitrile, methyl cyanoacetate and benzoylacetonitrile also produced the corresponding N-ylides, but other active methylene compounds such as malonates, ethyl acetoacetate and cyanoacetamide gave no ylide, only 2-substituted or/and 4-substituted products being formed. As for aromatic N-oxide, pyridine and isoquinoline N-oxides were inert to the N-ylide formation. On the other hand, quinoline 1-oxides bearing an electrondonating group at the 4-position, i.e., lepidine, 4-methoxy-and 4-amino-quinoline 1-oxides, were highly reactive toward this type of N-ylide formation. A likely reaction mechanism was proposed.

Oxydation photochimique d'amines tertiaires et d'alcaloideS—IX : Oxydation photochimique d'alcaloides quinolizidiniques et indolizidiniques tetracycliques: sparteine et α-isosparteine, lupanine et α-isolupanine, camoensidine et tetrahydroleontidine

The influence of ring size and ring conformation on the site of photosensitized oxidation of tertiary amines was illustrated by the photooxidation of tetracyclic indolizidine and quinolizidine alkaloids. An amino radical intermediate has been supposed during photooxidation of lupanine sensitized by eosin under nitrogen atmosphere.

Thermal elimination reactions of nitrones. Part 2. A mechanistic study based on substituent and solvent effects

The rates of thermal elimination of isobutene from a series of N-(diarylmethylene)-t-butylamine N-oxides have been measured by u.v. spectroscopy. Activation parameters derived for N-(fluoren-9-ylidene)-t-butylamine N-oxide in decalin and t-butyl alcohol solvents are consistent with an intramolecular concerted mechanism involving a highly ordered cyclic transition state. Kinetic results from the thermal elimination of para-substituted N-(diarylmethylene)-t-butylamine N-oxides in protic and aprotic solvents however suggest that the reaction proceeds via a non-synchronous concerted mechanism in contrast to the Cope elimination of tertiary amine oxides.

Reduction of tertiary amine N-oxide by purified cytochrome P-450

A reconstituted system containing cytochrome P-450 and NADPH-cytochrome c reductase, purified from phenobarbital-induced rabbit and rat liver microsomes, respectively, catalyzed anaerobic reduction of tiaramide N-oxide by NADPH at a rate comparable to that observed with intact rabbit liver microsomes. The reduction was inhibited by oxygen and carbon monoxide. When reduced methyl viologen was used as electron donor, the reduction proceeded at a much higher rate in the absence of NADPH-cytochrome c reductase. Preparations of various species of cytochrome P-450 purified from rabbit and rat liver microsomes and camphor-grown Pseudomonas putida exhibited nearly the same N-oxide reducing activity with reduced methyl viologen as donor despite their widely different specificities for hydroxylatable substrates.

Reduced nicotinamide adenine dinucleotide-dependent reduction of tertiary amine N-oxide by liver microsomal cytochrome P-450

NADH-supported reduction of tertiary amine N-oxides in rat liver microsomes was investigated with imipramine N-oxide, tiaramide N-oxide and N, N-dimethylaniline N-oxide as substrate in the presence of NADH. The reductase activity is sensitive to carbon monoxide. NADH-cytochrome b 5 reductase or cytochrome b 5, solubilized by trypsin or subtilisin, showed no N-oxide reductase activity. The NADH-dependent reduction of tertiary amine N-oxides was markedly inhibited by antibody to NADH-eytochrome b 5 reductase and antibody to cytochrome b 5. These results confirmed that NADH-dependent N-oxide reduction was catalyzed by cytochrome P-450 and the reducing equivalent for the N-oxide reduction was transferred from NADH to cytochrome P-450 mainly via NADH-cyto-chrome b 5 reductase and cytochrome b 5 in the microsomal membranes. NADH-dependent N-oxide reductase is also sensitive to oxygen and 4 μM oxygen gave 50 per cent inhibition with imipramine N-oxide. Kinetic study shows that K m values for the reduction of imipramine N-oxide, tiaramide N-oxide and N, N-dimethylaniline N-oxide were 0.05 mM, 0.14 mM and 0.16 mM, respectively. NADH-dependent N-oxides reductase activity is affected by azo and nitroso compounds and hydrazide, although the degree of inhibition was rather weak compared with those of NADPH-dependent activity. Furthermore, NADH-dependent reduction of tertiary amine N-oxide was only slightly affected by n-octylamine, 2,4-diehloro-6-phenylphenoxyethylamine and aniline. NADH-dependent N-oxide reductase activity in liver microsomes was less sensitive to phenobarbital or 3-methyleholanthrene pretreatment than NADPH-dependent activity. Some characteristics of NADH-dependent N-oxide reductase activity were discussed and compared with those of NADPH-dependent activity.

Reactions concerned in tertiary amine N-oxides. VIII. Oxidation of secondary alcohols (author's transl)

Reactions concerned in tertiary amine N-oxides. VIII. Oxidation of secondary alcohols (author's transl)

Studies on tertiary amine oxides. 59. A new total synthesis of dl-allomatridine.

1, 1-Ethylenedioxy-9-(2-pyridyl) quinolizidine (1) was converted to N-ethoxycarbonylpyridinium salt (3) via monohydrobromide (2) by successive treatment with ammonium bromide and ethyl bromoacetate. The reaction of 3 with hydrochloric acid was markedly affected with the concentration of the acid. Thus, when 3 was heated with 15-20% hydrochloric acid, ring closure took place accompanied by hydrolysis of the ketal and ester groups and also decarboxylation to give 17-hydroxy compound (4). Heating with triethylamine gave dehydrated pyridinium salt (5) which was reduced with sodium borohydride and then catalytically to dl-allomatridine (6). On the other hand, heating 3 with 5-10% hydrochloric acid gave a carboxylic acid (9) which was also transformed into 6 through an ester (10) and a ring closure product (11) as shown in Chart 2. The action of 30% acid on 3 followed by the similar treatments afforded 1-hydroxy-9-(2-pyridyl) quinolizidine (7). Transformation of 1 to 17-hydroxyallomatridine (8) was further achieved successively by hydrolysis to 1-oxo compound (12), formation of its cyanohydrin (13) and hydrogenation over Raney nickel.

Studies on tertiary amine oxides. LXI. Some reactions of 2-phenylquinoline 1-oxide and its derivatives.

The orientation of nitration of 2-phenylquinoline 1-oxide (1) with potassium nitrate and sulfuric acid was found to be principally governed by the concentration of sulfuric acid independently of the reaction temperature. Thus, whereas the reaction in concentrated sulfuric acid gave 3'-nitro derivative (3) as the main product, the use of 70-75% sulfuric acid was favorable for the formation of 4-nitro derivative (2). Further nitration of 2 and 3 readily produced 3', 4-dinitro compound (4). The Reissert-Henze reaction of 2-(4-methoxyphenyl) quinoline 1-oxide (7) afforded 1-benzoyloxy-4-cyano-1, 4-dihydroquinoline (12) besides 4-cyano (9), 6-benzoyloxy- (10) and 8-benzoyloxy-quinolines (11). From the reaction of 2-(4-nitrophenyl) quinoline 1-oxide (8), the corresponding 1, 4-dihydroquinoline (15) was also isolated together with 6-and 3-benzoyloxyquinolines (13 and 14). The mechanism of the formation of benzoyloxy derivatives was discussed.

Ei reaction of sulphilimines and related compounds

Ei reaction of tertiary amine oxides, i.e. the Cope elimination and that of sulphoxides, are briefly reviewed. N-p-Tosylsulphilimines also undergo facile Ei reaction upon heating and the stereospecificity of the reaction is better than that of the corresponding sulphoxides and even somewhat better than that of the tertiary amine oxides. A general outlook on research on the Ei reactions of sulphilimines and the mechanism of the reaction are discussed in comparison with those of similar Ei reactions which proceed via 5-membered cyclic transition states.

Thermal elimination reactions of nitrones. Part 1. Applications, limitations, and stereochemistry

A series of N-(fluoren-9-ylidene)alkylamine N-oxides has been synthesised by direct oxidation of the parent imines with peroxy-acid. Most of these nitrones underwent a thermal elimination reaction (analogous to the Cope elimination of tertiary amine oxides) to produce olefin and oxime products. The elimination reaction was followed by g.l.c. and mass and n.m.r. spectroscopic techniques, and the results are rationalised in terms of several factors including statistical and steric effects and olefin stability. The applications and limitations of this nitrone elimination reaction and the relationship between the stereochemistry of reactants and that of products has been examined for various nitrones R1R2CN+(O–)R3(R1= aryl, R2= H; R1 and R2 both alkyl; R1= alkyl, R2= aryl; R1 and R2 both aryl).

Stimulatory effect of FMN and methyl viologen on cytochrome P-450 dependent reduction of tertiary amine N-oxide

FMN or methyl viologen stimulated anaerobic reduction of tertiary amine N-oxides by liver microsomes and this stimulatory effect was completely inhibited by carbon monoxide. Spectral study indicated that FMN or methyl viologen is reduced by NADPH-cytochrome c reductase and reduced FMN or methyl viologen is reoxidized by cytochrome P-450 in the presence of tertiary amine N-oxides. In the presence of FMN, xanthine oxidase-hypoxanthine system rapidly reduced tiaramide N-oxides through the reduction of cytochrome P-450: the maximum reduction rate of tiaramide N-oxide was about 100 nmoles/mg protein/min.

Reactions of nitrogen compounds with ruthenium tetroxide. 2. Oxidation of tertiary amines as a convenient alternative to von Braun degradation

Reactions of nitrogen compounds with ruthenium tetroxide. 2. Oxidation of tertiary amines as a convenient alternative to von Braun degradation

An improved catalytic OsO 4 oxidation of olefins to [formula omitted]-1,2-glycols using tertiary amine oxides as the oxidant

An improved catalytic OsO 4 oxidation of olefins to [formula omitted]-1,2-glycols using tertiary amine oxides as the oxidant

Reactions concerned in tertiary amine n-oxides. VII. Reactions of Shiff's bases with amine N-oxides (author's transl)

With the Schiff base as a model compound, compounds possessing an azoxymethine group were reacted with pyridine 1-oxide (IIa) and triethylamine N-oxide (IIb), in the presence of a platinated palladium-carbon catalyst. Reaction of N-benzylideneaniline (I) with IIa gave benzanilide (III) and that of I with IIb gave 2-phenylquinoline (V) and not III. Reaction of I with fumaric acid and paraldehyde, in the presence of platinated palladium-carbon catalyst gave V in 23.3% yield. Reaction of 2-benzylideneaminophenol (VII) with IIa gave a small amount of 2-phenylbenzoxazole (VIII), while that with IIb for 7 days at room temperature gave VIII in 6% yield. It is considered that oxidation becomes too strong in the reaction of VII with an N-oxide. Reaction of VII by bubbling air through its xylene solution, using the platinated palladium-carbon catalyst, results in approximately quantitative yield of VIII. These reactions were also examined with the derivatives of VII.

Reactions concerned in tertiary amine n-oxides. VI. Reactions of 2'-hydroxychalcone derivatives with amine N-oxides (author's transl)

Reactions concerned in tertiary amine n-oxides. VI. Reactions of 2'-hydroxychalcone derivatives with amine N-oxides (author's transl)

Aryl migration in the Meisenheimer rearrangement

Migration of the benzene ring from nitrogen to oxygen in tertiary amine oxides is reported, and the mechanism is proposed as a concerted intramolecular cyclic process.

Studies on tertiary amine oxides. 58. Reactions of substituted dehydroquinolizidines with pyridine N-oxide. (2).

In order to introduce 2-pyridyl group into the 9 position of 1, 1-disubstituted quinolizidine, N-benzoyloxypyridinium chloride (1) was treated with 9-dehydro-1-oxoquinolizidine (3), dehydro-1-ethoxycarbonyl-1-hydroxyquinolizidine (13) and 9-dehydro-1, 1-ethylenedioxyquinolizidine (16) in dichloromethane, followed by reduction of the reactants with sodium borohydride in anhyd. ethanol. Although reactions with 3 and 13 gave no satisfactory result, that with 16 afforded the expected 1, 1-ethylenedioxy-9-(2-pyridyl)-quinolizidine (18) in 17% yield together with dehydro-1, 1-ethylenedioxy-x-(2-pyridyl)-quinolizidine (19). Other observations encountered in reactions of 1 with 3 or 13 as well as in transformation of 2 into 13 and 16 were also described in some detail.

Studies on tertiary amine oxides. LX. Reactions of 3,2'-diquinolyl 1-oxide with some nucleophiles in the presence of acylating agents (author's transl)

In order to explore the anticipated nitrone-like property of the N-oxide group of 3, 2'-diquinolyl 1-oxide (2), some usual nucleophilic reactions of 2 were examined and it was found that all attempted reactions proceeded normally. Thus, treatment with sulfuryl chloride, benzoyl chloride-potassium hydroxide solution, and benzoyl chloride-potassium cyanide gave 2- and 4-chloro (3 and 4), 2-hydroxy (6), and 2-cyano (7) derivatives, respectively. Reactions in the presence of acylating agents with ethanol-triethylamine, ethyl cyanoacetate, and 1-morpholinocyclohexene also afforded the respective 2-substituted products (10, 12, and 13) in the usual way.