Reaction of carboxylic acids with vinyl ethers under solvent-free conditions using molecular iodine as a catalyst.

The reaction of vinyl ethers with carboxylic acids using iodine as a catalyst under solvent-free conditions was investigated. The reaction of saturated carboxylic acids with vinyl ethers gave the corresponding esters. Mechanistic studies revealed the production of the adduct of the vinyl ether with the carboxylic acid, which then rearranged to form the ester. At low temperatures, the reaction of 2-(1-hydroxycyclohexyl)acetic acid (1) and butyl vinyl ether yielded a butyl ester. However, at a reaction temperature of 80°C, both the esterification and the elimination of a water molecule occurred, yielding the unsaturated butyl ester butyl 2-cyclohexenylacetate. The reaction of 2-((1S,2S,4R)-2-hydroxy-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetic acid (12) with butyl vinyl ether at low temperatures resulted in a mixture of four compounds. However, similar to the high-temperature (>60°C) reaction of 1, the esterification was accompanied by the elimination of a water molecule to give the unsaturated butyl ester (E)-butyl 2-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)acetate. While a γ-hydrogen was abstracted to form the endo-type double bond in the reaction of 1, an α-hydrogen was abstracted to form the exo-type double bond in the reaction of 12.

Reaction of olefins with nitriles under solvent-free conditions using molecular iodine as a catalyst in the presence of water.

The reaction of olefins with nitriles using iodine as a catalyst under solvent-free conditions was investigated. The reaction of cycloolefins, such as cyclopentene and cyclohexene, with benzonitrile using iodine as a catalyst produced both amide and heterocyclic compounds. The reaction of chiral (+)-camphene with benzonitrile produced racemic (±)-N-isobornylbenzamide (N-((1S,2S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)benzamide). This indicated that skeletal rearrangement of camphene as well as amidation occurred. The optimized conditions were determined to be as follows: temperature, 90°C; molar ratio of nitrile:alcohol:iodine:water, 1:5:0.2:1.0; and reaction time, 18 h. The yield was 87% under these conditions. The reaction of (+)-camphene also proceeded with the other aromatic and aliphatic nitriles to produce racemic isobornylamides. However, except for styrene, complex reactions occurred in the reactions of benzonitrile with other terpenic olefins.

Synthesis of carboxylic acids, esters, alcohols and ethers containing a tetrahydropyran ring derived from 6-methyl-5-hepten-2-one.

3-hydroxy acids, 3-hydroxy-3,7-dimethyloct-6-enoic acid (1) and 3-hydroxy-2,2,3,7-tetramethyloct-6-enoic acid (2), were prepared from 6-methyl-5-hepten-2-one, and they were subsequently used to prepare (2,6,6-trimethyltetrahydropyran-2-yl)acetic acid (3) and 2-methyl-2-(2,6,6-trimethyltetrahydropyran-2-yl)propanoic acid (4), respectively, via cyclization with an acidic catalyst such as boron trifluoride diethyl etherate or iodine. The reaction of carboxylic acids 3 and 4 with alcohols, including methanol, ethanol, and 1-propanol, produced the corresponding methyl, ethyl, and propyl esters, which all contained a tetrahydropyran ring. Reduction of carboxylic acids 3 and 4 afforded the corresponding alcohols. Subsequent reactions of these alcohols with several acyl chlorides produced novel esters. The alcohols also reacted with methyl iodide and sodium hydride to provide novel ethers. A one-pot cyclization-esterification of 1 to produce esters containing a tetrahydropyran ring, using iodine as a catalyst, was also investigated.

Amide synthesis from esters with nitriles under solvent-free conditions using molecular iodine as a catalyst.

The reaction of esters with nitriles, using iodine as a catalyst under solvent-free conditions, was investigated. For example, 1-phenylethyl acetate reacted with benzonitrile in the presence of iodine to afford the amide, N-(1-phenylethyl)benzamide. Addition of water was effective in promoting amidation. The most suitable conditions were investigated, and determined as follows: temperature = 80°C, molar ratio of nitrile:alcohol:iodine:water = 1:3:0.2:1.0, and reaction time = 18 h. The amidation reactivity depended on the stability of the cationic intermediate formed from the ester. Only the reaction of 2-phenylpropan-2-yl acetate with benzonitrile gave no amide compound; rather, the cyclic compound, 1,1,3-trimethyl-3-phenyl-2,3-dihydro-1H-indene was obtained in 90% yield. The reaction of (-)-bornyl acetate with benzonitrile produced the racemic amide compound, (±)-exo-N-isobornylbenzamide, in 82% yield.