Ketaller ve asetaller

Abstract

Aldehit ve ketonların, alkollerle asit katalizörlüğünde oluş turdukları asetaller ve ketaller; çok uzun yıllardan beri bilinmekte dir. Buna rağmen, asetal/ketal sentezleri ndeki sorunlar çoktur ve çözümleri için araştırmalar zamanımızda da sürmektedir. Karbonilin ve alkolün cinsi, sübstifcüentleri, katalizörün cinsi, kullanılan yön temin özellikleri; amaçlanan asetalin oluşup oluşamamasına veya veri min azalıp/artmasına neden olmaktadır. Reaksiyonlarda optimum koşul lar seçilememişse çok sayıda istenmeyen ürün oluşur. Bunlar enol-e- terler, karbonil bileşiğinin kendisi ile reaksiyonundan oluşan olası aldol ve aldol eliminasyonu ürünleri, asit ortamda gerçekleşebilecek halka- kapanması ürünleri, karbonil bileşiğindeki olası karbon-karbon çoklu bağlarına alkol katılması ile oluşabilen ürünler ve benzeri reaksiyonlardır. Bu çalışmada, terpen kökenli/kökensiz çok sayıda aldehit/keton ve alkol, iki farklı yöntem kullanılarak asetalleşme reaksiyonuna so kulmuştur. i) p-toluen sülfonik asit katalizörlüğünde çeşitli çözücülerdeki aze- otropik su distilasyonu yöntemi (Dean-Stark). ii) Asidi k katyon değişimirreçinesi/CaS04 yöntemi. Çalışmada; C4, C5 ve C7 düz zincirli aldehitlerin kokulu ter pen alkolleriyle asetalleşme! eri başarısız olmuştur. Diğer taraftan terpenoid kökenli metil ketonlar (meti 1 heptenon, B-iyonon, heptadesil- metilketon), sıklık ketonlar (1-menton, (-)-karvon) ve açık zincirli terpen aldehiti olan sitralin 1,2-diol ve 1,2,3-triollerle olan reak siyonlarında başarılı sonuçlar alınabilmiştir. Zaman zaman farklı iki yöntemden farklı ürünler elde edilmiş veya farklı iki yöntemden elde edilen aynı ürünün verimi farklı olabilmiştir. Elde edilen ü- rünlerin bazıları orijinaldir ve hemen hepsi güzel kokusuyla dikkat çekmektedir. Bu nedenle; kosmetik, deterjan, sabun, gıda, ilaç en düstrilerinde kullanılabilirlik özelliği göstermektedirler.

Ac eta Is are important in synthetic carbohydrate and steroid chemistry. In the pharmaceutical, phytoparmaceutical, fragrance and lacquer industries, acetals are used both as intermediates and as end products. Protection of the carbonyl group of aldehydes or ke tones can be accomplished by acetalization. The use of ah acetal (methylal) in the protection of the alcohol function is well known. Carboxylic acids can be prepared from protected aldehydes. Recently, asymmetric reductions of prochtral aromatic ketones in the presence of a hydroxymonosaccharide acetal have been described. Aîthough acetalization reactions occur in non-acidic medium, generally acetals from alcohols and aldehydes or ketones can be pre pared in acidic medium. The reaction is generally believed to proce ed through the formation of the corresponding hemiacetal. The equi librium of the acid-catalyzed reaction is controlled by the nucleop- hilic addition of the alcohol to the carbonyl group and not by the conversion of the hemiacetal to the acetal. R1 Rl OR3 ^0=0 + 2 R3-QH7 > NC + H20 R2/ R2/ \r3 R^ alkyl, aryl R2= H, alkyl, aryl Acetals derived from aldehyde are more easily formed than acetals derived from the corresponding ketone and cyclic acetals are generally more easily formed than open-chain acetals. Conjugation deactives the carbonyl function towards acetal © Obviously, sterically hindered alcohols react more slowly. Electron-with drawing groups enhance and electron-donating substi- tuents hinder acetal formation. The six-membered ring carbonyl function is more reactive in nucleoptvilic addition reactions than the five-membered. Acetal formation is also favoured by an increase vii in pressure. The main problem in the acetal formation in acidic medium is to shift the equilibrium to the right by reducing the water concent ration. In some cases it sufficies to keep the concentration of water low by the addition of a large excess of alcohol. However, in most cases it is necessary to remove the water formed by physical or chemical methods. In physical methods, there are two different ways to remove the water formed. i) Remove! of the water by (continuous) azeotropic distillation with an inert solvent or by usual distillation, eventually under redus ced pressure or aided by an inert gas stream. ii) Removel of the water by dehydrating agent such as calcium sulfate, aluminium oxide, copper sulfate, and molecular sieves. In chemical methods, the water formed in the reaction reacts immediately with the ortoester or dialkyl sulfite. The choice of the acid catalyst depends on its solubility, on the natut?e of the carbonyl compound and the alcohol, and on the reaction conditions. Acetalization of aldehydes can be performed in the presence of a weak acid such as ammonium chloride, ammonium nit rate, calcium chloride, zinc chloride, iron (III) chloride, tin (IV) chloride, or rare earth metal chlorides. Ketones generally need stronger acids such as sulfuric, hydro chloric, or p-toluene sulfonic acids. A ketone also requires a larger amount of catalyst than the aldehyde. Conjugated ketones require a larger amount of catalyst than the non-conjugated ones. Changes in the catalyst concentration influence the acetaliza tion rate but do not affect the equilibrium.Mild reaction conditions are required when side reaction may be expected by acids. In the preparation of a, e-unsaturated aeetals, migration of the double bond can be prevented by use of a catalyst with a pKa value not lower than 3. However, to ensure an acceptable reaction rate, the pKa value may not exceed 4. As summarized above, there are many unsolved problems in aceta lization reactions to obtain the desired products or to increase the yield of aeetals. If the optimum conditions can not be chosen several by-products such as enol ethers, aldols, aldol-eliminations, cyclizati- on products and addition products of alcohol used to the unsaturated carbon-carbon bonds present in the carbonyl compound may form. Vlll In this study, the reactions of terpenic/noh-terpenic aldehy- des/ketones with terpenic/non-terpenic alcohols were investigated using two different methods. i) Azeotropic distillation in acidic medium having p-toluenesulfonic acid using Dean-Stark apparatus (Tablo :'. 3). ii) Reaction in the presence of strong acidic ion-exchanger/anhydrous CaS04 (Table 4). To compare the reaction rates of the side- reactions the two methods above were also applied on the starting compounds invidually. (Table 1 and 2 ). Table 1 Reaction of The Starting Compounds with PTSA (Dean-Stark) (method i)* *mol ratio of PTSA/Starting compound: 0.003, solvent=petroleum-benzine Table 2 Reaction of Methyl heptenone and e-Ionone with Strong Acid Ion Exchanger/CaS04 (method ii) 1 Y Table 3 Acetalization Reactions=Removal of Water by Azeotropic Distillation (Method i) Table 3 (continued) R-CH-CH? o. OH OH o. (-)-Carvone R=CH3 R XI b OH R-CH-CHo choCh) i I <-.ufcHO) ' I V-O-CH _CH_R H{ } OH OH 1 2 CitraKcis+trans) R=CH3 U.. XIIb Ia=R=Ha [2~\ Va=R=CH3a IX =R=CH3 IIa=R=CH3a [3] VIb=R=Hb Xb=R=Hb IIIa=R=CH20H [3] VIIb=R=CH3b [5] XIb=R=CH3b IVa=R=Ha [4] VIIIb=R=Hb [ö] XIIb=R=CH3b a=Petroleum benzene (40-60°); b=Benzene Table 4 Acetalization Reactions=Removal of Water by Dehyrating Agent/Ion Exchanger (Method ii) Carbonyl Compound Alcohol Reaction Product CH3> \=CH-CH2-CH2-C-CH3 - f^ ch3 CH/ "7-0^" 4- X_CH_CH _CH _C -CH HC I 2 2 2 3 Methyl heptenone - 3 0H XIIIA xmB g-Ionone XIV XI Table 4 (continued) *"* OH OH L-Menthone ^o H-C=0 LHp~oHp VIb ol I I No reaction3 T och3 OH OH Vanillin a=Petroleum benzene (40-60°); b=Benzene Some of the products obtained are new compounds. The whole products having excellent sweet, fruity aromas, showed the properties of flavoring materials for cosmetic, detergent, polymers, soap and food industries. They also are useful as insect sex attractants and in the production of physiological active compounds such as steroids, prostaglandina and pharmaceutical skin penetration enhancers.