Halogenation cyclic acetal

A similar Co-catalyzed reaction with arylmagnesium halides and alkenes 181, bearing a halogen in a suitable position, occurs via a radical intermediate, leading to cyclic acetals 182 (equation 109). ... 

In this Section, hydrolysis, acetolysis, and isomerization of acetals are considered. Selective deprotection of acetals may also be achieved through halogenation, hydrogenolysis, ozonolysis, and photolysis, but these topics, are covered in an accompanying article in this Series, on the reactivity of cyclic acetals of aldoses and aldosides,3 and will not be discussed here. 

The halogen in the acylglycosyl halide is reactive and may be readily displaced, for example, by an alkoxy group on reaction with an alcohol under anhydrous conditions in the presence of a silver or mercury(n) salt. In this case the products are glycosides which are the mixed cyclic acetals related to the cyclic hemiacetal forms of the monosaccharides. In the case of the D-glucose derivative shown below (and of other 1,2-cis acylglycosyl halides) the replace-... 

Such reactions have preparative value when the halo ether is easily accessible by halogenation of an ether. For example, 2,3-dichlorodioxan and ethanol yield the cyclic acetal of glyoxal 935 and cyclic acetals of 2-chloro-4-hydroxy-butyraldehyde are formed from 2,3-dichlorotetrahydrofuran and alcohols 936, 937... 

X = Cl. Br. T Treatment of polystyryl diphenylphosphine with CL, Br, or I, in CH,CL.24 Halohydrins from epoxides yields and selectivities compare well with those obtained with monomeric triphenyl phosphine-halogen complexes.2 11 Open and cyclic acetals and thioacetals by treatment of aldehydes and ketones with alcohols or thiols in the presence of polystyryl diphenylphosphine iodine complex.249... 

In pyridine and with a suitably blocked derivative, the same reagent can be used selectively to introduce sulfate acid ester groups thus, 1,2 5,6-di-O-isopropylidene-D-glucose can be sulfated, and, on removal of the cyclic acetal groups, D-glucose 3-sulfate can be obtained as a suitable salt. Sulfur trioxide or chlorosulfonic acid in liquid sulfur dioxide, and sulfur trioxide in halogenated hydrocarbon solvents, pyridine, or iV,A -dimethylforma-mide, can also be employed for sulfation. 

L-Ascorbic acid reacts as a Michael donor with acrolein or methyl vinyl ketone the products can be converted to cyclic acetals as shown in Scheme 5- The analogue (15) of ascorbic acid has been made as indicated in Scheme 6 the halogen at C-3... 

Halogenation of the 7 position also proves compatible with good antiinflammatory activity. Construction of this compound, aclomethasone dipropionate (80), starts by introduction of the required unsaturation at the 6,7 position by dehydrogenation with DDQ (76). The highly hindered nature of the hydroxyl at position 17 requires that a roundabout scheme be used for formation of the corresponding ester. Thus treatment of 76 with ethyl orthoformate affords first the cyclic orthoformate This then rearranges to the 17 ester on exposure to acetic acid. Acylation of the 21 alcohol is accomplished in straightforward fashion with... 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

Synthesis of Five-membered Cyclic Nitronates from a-Halogen-substituted AN. The key step of this approach is presented in Scheme 3.1, path (b). Until recently, this synthetic route to nitronates (24) has been of no preparative interest, because only two examples, such as elimination of trimethylsilyl nitrite (75) and 1,2-dinitrophenylethane (85) from the corresponding nitroso acetals were documented. 

Truce and Norrell noticed in 1963 that sulfenes readily undergo 2 - - 2 cycloaddition to ketene diethyl acetal with the formation of 3,3-diethoxythie-tane 1,1-dioxides. The same reaction was carried out by Paquette, using 1,1-dioxide ketals with cyclic a-halo sulfones in which the corresponding chloroketal derivatives 47 were formed. This approach may be illustrated by the addition of ketene diethyl acetal to halogenated sulfenes and to... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

Table 6 includes data on three halogenations of tetraalkylmetals. The iodode-metallation of tetramethyltin in solvent methanol no doubt proceeds by mechanism SE2(open)10, and the calculated value of Z ( 0.32) is compatible with such an assignment. However, the positive salt effect on the bromodemetallation of tetra-isopropyltin in solvent acetic acid (e20 = 6.15) is quite small, and leads to a value of only 0.28 for Z2d and a corresponding value of 0.22 for Z, assuming (see p. 148) that d is approximately 6 A. Here is a possible case, therefore, of a mechanism that is in the intermediate SE2(open)-SE2(cyclic) region. 

The carbinol precursor of propoxyphene is made by treating the Mannich base 21a with a benzyl Grignard reagent. The major (a) diastereoisomer 21b is separated, resolved with (+)-camphor-10-sulfonic acid, and finally acylated to yield the active drug. Pyrrolidino analogs of propoxyphene are more potent than the parent (acetate, 2 x, propionate,1 x pethidine in mice),(51) while the halogenated acetates 22 (X = F or Cl) have similar activities to morphine in mice.(58) Replacement of terminal phenyl of propoxyphene by 2-pyridyl achieves a potency rise, as occurs also in the cyclic analog 23/59 ... 

The reaction of carbonyl compounds with glycerin-a-monochlorohydrin, CHjOHCHOHCHjCl, leads to cyclic halo acetals. Treatment of a,/3-olefinic aldehydes with alcohols saturated with dry hydrogen chloride causes the addition of the halogen acid to the double bond as well as acetalization to give /3-halo acetals. ... 

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