Methyl Hemiacetal Research Articles

The chemistry of small ring compounds. Part 29: Synthesis and stereochemistry of some arylcyclopropanone methyl hemiacetals and their acetates

AbstractSome mono‐aryl substituted 1‐methoxycyclopropanols (cyclopropanone hemiacetals) with the following aryl groups, C6H5‐, p‐CH3C6H4‐ and p‐ClC6H4‐, have been prepared in 80‐85 % yield by passing ketene at −70°C into a solution of aryldiazomethane in CFCl3 or CCl4, containing an excess of methanol, which adds to the intermediate arylcyclopropanone. It appears that the addition of methanol to the carbonyl group in the arylcyclopropanone takes place preferentially at the least hindered side of the cyclopropyl ring as is shown by structure elucidation (NMR) of the more stable acetates derived from the hemiacetals.

The chemistry of small ring compounds. Part 30. Reactions of arylcyclopropanone hemiacetals with bases and acids

AbstractThe arylcyclopropanone methyl hemiacetals (aryl = C6H5, p‐ClC6H4 and p‐CH3C6H4) are quantitatively isomerised by sodium methoxide or tert‐amines to propionic esters. The ring fission is rapid and occurs exclusively at the C1‐C2 position, leading to products derived from the most stable incipient carbanion.The hemiacetals react with acids via a Woodward‐Hoffmann cleavage of the C1‐C3 cyclopropyl bond, affording a mixture of 1‐ and 3‐substituted arylacetones, the ratio of which depends on the nature of the acid. This acid‐catalysed C2‐C3 ring‐fission only occurs when an aryl group is present. The unsubstituted cyclopropanone hemiacetal isomerises in (weak) acid to the propionic ester (C1‐C2 rupture).The transformation of arylcyclopropanone methyl hemiacetals in acidified methanol to α‐aryl‐α‐methoxy‐acetones, is first order in the hemiacetal. From the rate constants a Hammett ρ value of −0.7 is obtained, thus showing a small interaction of the aryl group with the remote reaction centre. This is considered to support a mechanism in which arylcyclopropanone is an essential intermediate. Subsequent protonation of this ketone with simultaneous C2‐C3 bond rupture gives the substituted 2‐hydroxyallylic cation. For this step an approximate ρ value of −2.9 is calculated, thus indicating that this step is much more sensitive to the presence of a (para) substituent in the aromatic ring. Further evidence for the occurrence of an intermediate arylcyclopropanone is the alkoxy exchange in the starting material when CD3OD or n‐propanol is used as solvent. The proposed mechanism is also consistent with the observed stability of the corresponding arylcyclopropanone acetals under similar acidic conditions.

The Crystal and Molecular Structure of Vitamin B6 Derivatives. I. Pyridoxal Phosphate Hydrate and Pyridoxal Phosphate Methyl Hemiacetal

Abstract Pyridoxal phosphate hydrate (PLPHYD) was crystallized from an aqueous solution in the form of monoclinic needles; space group P21⁄c with a=10.503, b=13.608, c=7.488 Å, β=93.71° and four molecules in the unit cell. Prism-shaped crystal of pyridoxal phosphate methyl hemiacetal (PLPMHA) was obtained by dissolving the pyridoxal phosphate hydrate crystals into 90% methanol; space group P\barl, with cell dimensions, a=9.42, b=10.61, c=6.20 Å, α=105.6°, β=95.7°, and γ=99.7°, and two molecules per cell. Intensity data were collected on an automated diffractometer for PLPHYD and photographically for PLPMHA. Crystal structures have been determined by the symbolic addition method. Refinements were done by the block-diagonal least-squares procedures, the final R value being 0.093 for PLPHYD and 0.112 for PLPMHA. The free aldehyde group of pyridoxal phosphate interacts with water molecule to form gem-diol in the crystalline state of PLPHYD and the gem-diol group of PLPHYD with methanol to form methyl hemiacetal. One of the two hydrogen atoms on a phosphate group is liberated and protonated to the pyridine ring nitrogen atom, resulting in the zwitterionic structure for both PLPHYD and PLPMHA molecules. All hydrogen bonds in PLPHYD are intermolecular ones, but in PLPMHA there is one OH–O intramolecular hydrogen bond.

The chemistry of small ring compounds—XX : Cidnp effects in the oxidation of 2,2-dimethylcyclo- propanone methyl hemiacetal

Mild oxidation of 2,2-dimethylcyclopropanone methyl hemiacetal ( 1) with oxygen, t-butyl- hydroperoxide or di t-butylperoxalate leads to hydrogen abstraction from the OH group of 1. The cyclopropyl ring probably breaks simultaneously to give ring-opened tertiary radical 3a and primary radical 3b. In CDCl 3, CIDNP effects are observed in the saturated disproportionation product of 3a and also in products resulting from disproportionation and combination of 3a with solvent derived CCl3 3 and CDCl 2 radicals. The large difference in g-values between individual radical components in each of these latter pairs explains the observed emissions. In benzene, solvent does not interfere and CIDNP effects mainly arise from radical pairs, consisting of identical components, e.g. two radicals 3a or at least of components with practically equal g-values. Thus disproportionation leads to absorption-emission (multiplets effects) for the unsaturated esters 5 and 6 and the isovalerate 8.

Displacement reactions of acyclic carbohydrate derivatives. II. A 1,4-methoxyl group migration following acetal participation: 4-O-methyl-l-lyxose.

The benzoate displacement reaction on 2,3,5-tri-O-benzyl-4-O-toluene-p-sulphonyl-D-ribose dimethyl acetal gave not the expected 4-O-benzoyl-2,3,5-tri-O-benzyl-L-lyxose dimethyl acetal but the isomeric 1-O-benzoyl-2,3,5-tri-O-benzyl-4-O-methyl-L-lyxose methyl hemiacetal as a consequence of methoxyl group participation and migration. The structure of the product was determined by conversion into the known 4-O-methyl-L-lyxitol (2-O-methyl-L-arabinitol) and into 4-O-methyl-L-lyxose. 4-O-Methyl-D-lyxose has been synthesised.

Phenylhydrazono-phenylazo tautomerism : Part I. xylo-4,5,6-trihydroxy 2-oxo-1,3-bis(phenylhydrazono)cyclohexane and 4-oxo-1-phenyl-5-phenylazo-3-pyridazine derivatives

The positions of the phenylhydrazono groups in xylo-4,5,6-trihydroxy-2-oxo-1,3-bis(phenylhydrazono)cyclohexane were established by degradation of the compound with sodium metaperiodate and identification of the reaction product. The dialdehyde initially formed by periodate oxidation (but not isolated) cyclized to 4-oxo-1-phenyl-5-phenylazo-3-pyridazinecarboxaldehyde, which gave a crystalline methyl hemiacetal, an oxime, a semicarbazone, and, by oxidation, the corresponding monocarboxylic acid and sodium salt. Upon treatment with phenylhydrazine at 50°, the carboxaldehyde gave a red, crystalline phenylhydrazone which, with phenylhydrazine at 130°, gave a product that appears to be 4-oxo-1-phenyl-5-phenylhydrazo-3-pyridazinecarboxaldehyde phenylhydrazone. The reactions provide a route to a series of pyridazine derivatives which may prove valuable for the synthesis of unusual compounds for biological and medical research. xylo-4,5,6-Trihydroxy-2-oxo-1,3-bis(phenylhydrazono)cyclohexane exists in a yellow keto form and in a red enolic form. On warming in toluene, the yellow form gives the red form, which has an enolic phenylhydrazono-phenylazo structure.