Interesting Alcohols, Ethers, and Epoxides

A large number of alcohols, ethers, and epoxides have interesting and useful properties. 

For compounds of comparabie moiecuiar weight, the stronger the intermolecular forces, the higher the bp or mp. 

Increasing ability to hydrogen bond Increasing boiling point 

Alcohols, ethers, and epoxides having 5 C s are H2O soluble because they each have an oxygen atom capable of hydrogen bonding to H2O (Section 3.4C). 

Problem 9.8 Rank the following compounds in order of increasing boiling point. 

Problem 9.9 Explain why dimethyl ether (CEl3)20 and ethanol (CEI3CEI2OEI) are both water soluble, but the boiling point of ethanol (78 °C) Is much higher than the boiling point of dimethyl ether (-24 °C). 

Since green plants use sunlight to convert CO2 and H2O to carbohydrates during photosynthesis, next year s com crop removes CO2 from the atmosphere to make new molecules of starch as the com grows. While in this way ethanol is a renewable fuel source, the need for large-scale farm equipment and the heavy reliance on fertilizers and herbicides make ethanol expensive to produce. Moreover, many criticize the use of valuable farmland for an energy-producing CTOp rather than for food production. As a result, discussion continues on ethanol as an alternative to fossil fuels. 

Methanol (CH3OH) is also called wood alcohol, because It can be obtained by heating wood at high temperatures in the absence of air. Methanol is extremely toxic because of the oxidation products formed when it Is metabolized in the liver (Section 12.14). Ingestion of as little as 15 ml causes blindness, and 100 ml causes death. 

---

One of the most interesting papers on ascorbic acid-Cu reactions showed that ascorbic acid-Cu catalyzes the formation of ethylene from several precursors. The interest in ethylene was as an abscission agent in plants. All alcohols, aldehydes, acids, ethers, and epoxides formed ethylene when mixed with Cu and ascorbic acid in 5-mL closed bottles at 30 °C for 1 h. Methional was the most active, followed by propanal, propanol, propyl ether, ethyl ether, and ethanol. This reaction may be part of the oxygen scavenging system because Cu increases ascorbic acid s ability to scavenge oxygen. The authors claim this reaction cannot be attributed to copper in its lower valence state. 

The alkylations of arenes by alcohols, ethers and esters, as well as with epoxides and lactones, are of considerable interest, and constitute a significant part of the field of Friedel-Crafts alkylations. Some of the earliest examples are the alkylations of arenes with primary alcohols, esters and ethers. < Subsequent work over the years has revealed that these alkylations are often accompanied by various side... 

The interdigital secretion of the red hartebeest, A. b. caama, consists of fewer compound classes. It contains a few alkanes and short-chain, branched alcohols, fatty acids, including a few of the higher fatty acids up to octadecanoic acid, an epoxide and the cyclic ethers, rans-(2 ,5.R)-furanoid linalool oxide 23, as-(2JR,5S)-furanoid linalool oxide 24 and ds-(2S,5i )-furanoid linalool oxide 25 (Fig. 5) in a ratio of 2.5 1 1.5 respectively [138]. From the point of view that many of the constituents of the interdigital secretion of this animal are probably of microbial origin, it is interesting that cis- and trans- furanoid linalool oxides have also been found in castoreum [77]. 

Cyclization of allylic alcohols to form epoxides has been particularly problematical, and the reactions have been more of mechanistic than of synthetic interest. For reactions conducted under basic conditions, it is possible that epoxide formation involves initial halogen addition followed by nucleophilic displacement to form the epoxide. Early examples of direct formation of epoxides from allylic alcohols with sodium hypobromite," bromine and 1.5 M NaOH,12 and r-butyl hypochlorite13 have been reviewed previously.fr Recently it has been shown that allylic alcohols can be cyclized effectively with bis(jym-collidine)iodine(I) perchlorate (equation 3).14 An unusual example of epoxide formation competing with other cyclization types is shown in equation (4).15 In this case, an allylic benzyl ether competes effectively with a -/-hydroxyl group as the nucleophile. 

A very interesting reaction of an epoxide with WC16 provides the trans-dichloride <07TL8388>. The reaction proved compatible with a number of functional groups including esters, sulfones, and even silyl ethers (with the addition of 2,6-di-t-butyl pyridine). Olefins and alcohols were converted to the chlorides. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

An interesting alcoholysis of epoxides has been reported by Masaki and coworkers <96BCSJ195>, who examined the behavior of epoxides in the presence of a catalytic amount of the Tt-acid tetracyanoethylene (TCNE, 85) in alcoholic media. Ring-opening is very facile under these conditions, typically proceeding via normal C-2 attack, as exemplified by styrene oxide (86). Certain epoxy ethers (e.g., 89) undergo C-1 attack due to anchimeric assistance. Analysis of the reaction mixtures revealed the presence of captodative ethylenes (e.g., 85) formed in situ, whieh were shown to be aetive in eatalyzing the reaction. The proposed mode of catalysis is represented by the intermediate 87. The affinity of these captodative olefins for... 

Interestingly, MCPBA epoxidation of cis alcohol 16 affords a mixture of diastereomeric epoxides (55 45 mixture). Furthermore, protection of the allylic alcohol as TBS ether (17) and subsequent epoxidation results as well in hardly any stereochemical selectivity (53 47 mixture). With regard to these results it is suggested that the trans-allylic hydroxy group is effectively involved in directing the MCPBA epoxidation event. 

The epoxy alctrfiol (97), a key intermediate in the synthesis of maytansine, has been prepared through Ti-catalyzed epoxidadon of (95 equation S6). The alcohol (95) exists predominantly in confoimation (162), with the allylic hydrogen at C-4 and the ir-bond very nearly eclipsed. The oxygens of the alcohol and silyl ether which are located below the plane the ir bond complex with Ti this complex blocks the approach of the epoxidizing reagent fitom the a-fu and hence the P-epoxide is fmmed. It is of interest to note that the ir-facial selectivity resulting fiom this route is the opposite of the ir-facial selectivity observed in MCPBA epoxidadon (see equadon 33). 

---