Dioxan 4-phenyl

Phenyl-2-cyclopenten-l-one -Phenyl-A/,APdielhanolamine 2-Phenyl-1,3-dioxane 4-Phenyl-1,3-dioxane... 

A reaction carried out by Haruki et al. is the energic oxidation of 5-(l-hydroxyethyl)2-phenylthiazole (5) in dioxane by aqueous Kl-iodine to give 2-phenyl-5-thiazolecarboxylic acid (6) (Scheme 2) (28). 

For example, 2-phenyl-5-fonnylthiazole treated with AgjO in water and dioxane under basic conditions gives 2-phenyI-5-thia201ecarboxylic acid (29). 

Peroxides. These are formed by aerial oxidation or by autoxidation of a wide range of organic compounds, including diethyl ether, allyl ethyl ether, allyl phenyl ether, dibenzyl ether, benzyl butyl ether, n-butyl ether, iso-butyl ether, r-butyl ether, dioxane, tetrahydrofuran, olefins, and aromatic and saturated aliphatic hydrocarbons. They accumulate during distillation and can detonate violently on evaporation or distillation when their concentration becomes high. If peroxides are likely to be present materials should be tested for peroxides before distillation (for tests see entry under "Ethers", in Chapter 2). Also, distillation should be discontinued when at least one quarter of the residue is left in the distilling flask. 

The preferred conformations of both 1-methyl-l-phenylcyclohexane and 2-methyl-2-phenyl-l,3-dioxane have the phenyl group in the axial orientation even though the conformational flee energy of the phenyl group (2.9 kcal) is greater than that for a methyl group (1.8 kcal). Explain. 

Some authors use O] instead of cr as the substituent constant in such correlations.) An example is provided by the aminolysis of phenyl esters in dioxane the substrates RCOOPh were reacted with -butylamine, and the observed first-order rate constants were related to amine concentration by = k2 [amine] kj [amine]. The rate constants kz and k could be correlated by means of Eq. (7-54), the reaction constants being p = +2.14, b = + 1.03 (for A 2) and p = -1-3.03,8 = -1-1.08 (for ks). Thus, the two reactions are about equally sensitive to steric effects, whereas the amine-catalyzed reaction is more susceptible to electronic effects than is the uncatalyzed reaction. 

The enamines derived from cyclic ketones give the normal alkylated products, although there is some evidence that unstable cycloadducts are initially formed (55b). Thus the enamine (28) derived from cyclohexanone and pyrrolidine on reaction with acrylonitrile, acrylate esters, or phenyl vinyl sulfone gave the 2-alkylated cyclohexanones (63) on hydrolysis of the intermediates (31,32,55,56). These additions are sensitive to the polarity of the solvent. Thus (28) in benzene or dioxane gave an 80% yield of the... 

Pyridine-2-carbaldoxime, TEA, H2O, dioxane. The 2-(l-methyl-2-imida-zolyl)phenyl group is not removed under these conditions. ... 

Dicyano-2,4,8-triphenyl-7-phenylsulfonyl-6/f-pyrido[], 2-a]pyrimi-dine-6-thione was obtained in the reaction of 6-amino-1-benzoyl-5-cyano-4-phenyl-3-phenylsulfonylpyridin-2(]//)-one and benzylidenemalononitrile in the presence of piperidine in boiling dioxane for 4h in 59% yields (98M1049). 

An interesting method of forming 2-oxo-3-phenyltetrahydro-l,3 oxazine (19) and its derivatives was recently given by Gulbins et at. It consists of heating a 2-oxo-l,3-dioxane with phenyl isocyanate ... 

Reaction of anthanilic acid 112 with acid anhydrides afforded the corresponding imide derivatives 113. Subjecting 113 to intramolecular Wittig cyclization has been achieved by treatment with A-phenyl(triphe-nylphosphoranylidene)etheneimine in toluene or dioxane whereby the corresponding pyrroloquinolines 116 were obtained (94TL9229). The intermediate 115 resulting from the rearrangement of 114 could be isolated when the reaction was done at room temperature (Scheme 22). 

Early efforts to effect the photoinduced ring expansion of aryl azides to 3H-azepines in the presence of other nucleophiles met with only limited success. For example, irradiation of phenyl azide in hydrogen sulfide-diethyl ether, or in methanol, gave 17/-azepine-2(3//)-thione35 (5% mp 106—107 " O and 2-methoxy-3//-azepine (11 %),2 3 respectively. Later workers194 failed to reproduce this latter result, but found that in strongly basic media (3 M potassium hydroxide in methanol/dioxane) and in the presence of 18-crown-6, 17/-azepin-2(3//)-one was produced in 48% yield. In the absence of the crown ether the yield of azepinone falls to 35%. 

A 7-chloro-5-phenyl-l//-l,3,4-benzotriazepine-2(3//)-thione24 (2.5 mmol) in dioxane (l 5 mL) was treated with powdered Pb(OAc)2 (1.63 g. 5 mmol) and an amine was passed for 30 min into the suspension. The mixture was left for a specified time. H,S was passed through the mixture and the precipitated lead sulfide was filtered off. The filtrate was evaporated in a stream of air to leave the product, which was recrystallized (cyclohexane). 

A solution of 1-phenyl-1//-pyrazolo[3,4-rf]pyridazinc-7-carbonitrilc (150 mg. 0.68 mmol) and A,A-diethyl-prop-l-ynamine(151 mg, 1.36 mmol) in l,4-dioxane(2 mL) was refluxed for 5 h. After cooling, the reaction mixture was poured onto excess ice, and extracted with CHC13. The extract was washed with H20, dried (Na2S04) and concentrated under reduced pressure. Purification by chromatography (silica gel, benzene then bcnzene/EtOAc 20 1) gave, from the benzene eluate, 6-diethylamino-1 -phenyl-1 //-indazole-7-carbo-nitrile [yield 81 mg (39 %) mp 104-105 C (benzene/petroleum ether)] as slightly yellow prisms and, from the second eluate, the diazocine 5 as yellow needles yield 90 mg (40 %) mp 121-122 C (benzene/ petroleum ether). 

S,5S,5 S)-5-(2-Alkfiiylmninoy or (4S,5S,5 S)-5-(2-Alkynylamino)-2,2-dimethy 1-4-phenyl-1,3-dioxane 9 3.91 g (10.5 mmol) of CeCI, 7H,(> is dried in vacuo at 140T70.5 lorr for 2 h. The following operations arc performed under argon protection. After cooling to r.t. 50 mL of anhyd THF is added and the resulting colorless slurry is stirred for 2 h under assistance of ultrasound. Subsequently, the suspension is cooled to... 

To the solution of (4S,5S, 5 S,)-5-(2-alkenylarnino)- or (4S,5S ,5 S )-5-(2-alkynylamino)-2,2,-dimethyl-4-phenyl-1.3-dioxane 9 obtained above in 30 raL of Et20 are added dropwise 30 mL of3N HC1 at 0 CC. Then the mixture is allowed to warm to r.t. over 12 h. The resulting precipitate is rccrystallizcd from CH2C12/Et20 (1 1) and treated with 2.5 N NaOH to provide the amino diol 10 which is extracted with 300 mL of Et,0 yield 81 87%. 

In asymmetric Strecker synthesis ( + )-(45,55 )-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has been introduced as an alternative chiral auxiliary47. The compound is readily accessible from (lS,25)-2-amino-l-phcnyl-l,3-propancdioI, an intermediate in the industrial production of chloramphenicol, by acctalization with acetone. This chiral amine reacts smoothly with methyl ketones of the arylalkyl47 or alkyl series48 and sodium cyanide, after addition of acetic acid, to afford a-methyl-a-amino nitriles in high yield and in diastereomerically pure form. 

S)-2-Cyano-l-(3,4-diraethoxyphenyl)-l-raethylethylamino -2,2-dimethyl-4-phenyl-l,3-dioxane Typical Procedure47 ... 

A solution of 20.7 g (0.1 mmol) of (46 ,56 )-5-amino-2.2-dimethyl-4-phenyl-l,3-dioxane and 19.4 g (0.1 mol) of 3,4-dimethoxyphenyl-2-propanone in 70 mL of CH3OH is warmed to 60 "C and 9 mL of acetic acid is added. After 15 min the mixture is cooled with an ice bath. The precipitated product is filtered off, stirred with 1 L of water for 1 h to dissolve inorganic salts, and again collected by filtration. Drying over NaOH and recrystallization from CH3OH gives the product yield 33.6 g (82%) mp 127 128°C [a] 2 + 85.7 (c = 1, CHC1,). 

The (/ (-enantiomer of 5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has also been successfully used for asymmetric Strecker syntheses4In addition, the acetal protecting moiety of the auxiliary has been modified. No significant change in the Strecker syntheses of a-mcthylamino nitriles has been reported for these alternative auxiliaries50. 

Table 1. Stereoselective Synthesis of a-Hydrogcnamino Acids Using 5-Amino-2,2-dimethyl-4-phenyl-1,3-dioxane as the Auxiliary51 53...

As with the 5-amino-4-phenyl-l,3-dioxane auxiliary47 53, the rert-leucine ester group has to be removed by oxidative degradation, in this case by a regioselective decarboxylation using fe/7-butyl hypochlorite. The expense of this auxiliary, coupled with its destruction, limits the practical value of this interesting procedure. 

The number of reactions that fit into this second class are manifold. Some typical examples are the amine-catalyzed reactions of 2,4-dinitrochlorobenzene with n-butylamine in chloroform (k"/k = 2.59 l.mole-1)23, with allylamine in chloroform (k"jk — 4.60 l.mole-1)24 and with allylamine in ethanol (k"fk =0.36 l.mole-1)25 and the amine-catalyzed reaction of p-nitrofluorobenzene with piperidine in polar solvents (k"/k < 3.2 l.mole-1)26. A typical example of a strongly catalyzed system is the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in 60 % dioxan-40 % water27. 

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

Oxidation of phenyl hexyl sulphide with sodium metaperiodate gave also only a trace amount of the corresponding sulphoxide72. On the other hand, Hall and coworkers73 prepared benzylpenicillin and phenoxymethyl penicillin sulphoxides from the corresponding benzyl esters by oxidation with sodium metaperiodate in dioxane solution with a phosphate buffer. A general procedure for the synthesis of penicillin sulphoxides was reported later by Essery and coworkers74 which consists in the direct oxidation of penicillins or their salts with sodium metaperiodate in aqueous solution at pH 6.5-7.0. 1-Butadienyl phenyl sulphoxide 4475 and a-phosphoryl sulphoxides 4576 were also prepared by the same procedure. 

Endprodukt der Reduktion von Hydroxy- und 1,3-Dihydroxy-accton in Ammo-niak/Ammoniumchlorid (pH 9,3) an Quecksilbcr (—1,7 V) ist Aceton5. In waGrigcm 1,4-Dioxan (Leitsalz Natriumacetat) erhalt man bei 75-80° aus 4,4 -Dimethoxy-benzoin 70°/(1 d.Th. /-Oxo-1,2-bis- 4-methoxy-phenyl]-athan6. 

Aspects of Stereochemistry, Part IV. Configuration and Some Reactions of 1 3-0-Benzylideneglyc-erols (5-Hydroxy-2-phenyl-1 3-dioxans), N. Baggett, J. S. Brimacombe, A. B. Foster, M. Stacey, and D. H. Whiffen,7. Chem. Soc., (I960) 2574-2581. 

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