Trans-1,4-Cyclohexanediol

Cyclohexanone 98.2 Cyclohexane, cyclohexanol Urine 0.5mgl cyclohexanediol, trans , 4-cyclohexanediol (alcohol metabolites excreted mainly as glucuronides in adults) See entry for cyclohexanol above... 

Stoddart and his coworkers have reported syntheses of the trans-syn-trans and the trans-anti-trans isomers of dicyclohexano-18-crown-6 The synthesis of these two compounds from trans-l,2-cyclohexanediol was accomplished in two stages. First, the diols were temporarily linked on one side by formation of the formal, and this was treated with diethylene glycol ditosylate and sodium hydride to form the hemi-crown formal. Removal of the formal protecting group, followed by a second cychzation completed the synthesis. The synthesis of the trans-anti-trans compound is illustrated below m Eq (3 12) and the structures of the five possible stereoisomers are shown as structures 1—5. 

MeC(OTMS)=CH2, coned. HCl or TMSCl, 10-30 min, 80-85% yield. " This method is effective for the formation of cis- or tran -acetonides of 1,2-cyclohexanediol. 

In a 250-ml three-necked flask fitted with a magnetic stirrer, a pressure-equalizing dropping funnel, and a thermometer is placed a solution of l,4-cyclohexanediol(l 1.4g, 0.10 mole), 35 ml of chloroform, and 27 ml of dry pyridine. The solution is cooled in an ice bath to 0-5 and is maintained below 5 throughout the addition. A solution of benzoyl chloride (14 g, 0.10 mole) in 30 ml of dry chloroform is added with stirring at a rate so as to keep the temperature below 5° (approx. 40 minutes). After completion of the addition, the mixture is allowed to come to room temperature and stand overnight. The chloroform solution is washed four times with 50-mI portions of water, once with 50 ml of 5 % sulfuric acid solution, and finally with saturated sodium chloride solution. The chloroform solution is then dried (sodium sulfate), and the solvent is removed. Fractionation of the residue gives a cis and trans mixture of 4-benzoyloxycyclohexanol, bp 175-17870.2 mm, as a very viscous oil, yield about 55%. 

As noted at the end of Section 7.8, the prefixes cis- and trans- would be ambiguous when naming the diols derived from 1-methylcyclohexene because the ring has three substituents. Instead, a reference substituent r is chosen and other substituents are either cis (c) or trans (f) to that reference. For the two l-methyl-l,2-cyc ohexanediol isomers, the -OH group at Cl is the reference (r-1), and the -OH at C2 is either cis (c-2) or trans (t-2) to that reference. Thus, the diol isomer derived by cis hydroxylation is named l-methyl-r-l,c-2-cyc ohexanediol, and the isomer derived by trans hydroxylation is named l-methyl-r-l,t-2-cyclohexanediol. 

Pimelic Acid (Heptanedioic Acid or 1,5-Pentane-dicarboxytlc Acid). HOOC.(CH2)s.COOH mw 160.17 white prisms mp 106° bp 272° at 100mm (subl), and 212° at 10mm d 1.329 g/cc at 15°. Sol in w, ethanol, eth and hot benz. Prepn is by oxidn of cycloheptanone, capric acid or oleic acid treatment of salicylic acid with Na in amyl ale, or by decarboxylating 1,1,5,5-pentanetetracarboxylic acid with heat Pimelic acid has been combined with cis and trans-, 4-cyclohexanediol to give polyesters, and with m-xylene-ce,ol -diamine or poly-methylenediamines to form polyamides. With diperoxides, the acid forms resins. It is also used as the parent compd to form the expls presented below... 

A. trans-l,2-Cyclohexanediol. In a 100-ml., round-bottomed flask equipped with a reflux condenser protected with a drying tube are placed a magnetic stirring bar, 17.56 g. (0.0667 mole) of thallium (I) acetate (Note 1), and 40 ml. of dried acetic acid (Note 2). The mixture is stirred and heated at reflux for 1 hour. To the cooled mixture are added 2.84 g. (3.5 ml., 0.0346 mole) of cyclohexene (Note 3) and 8.46 g. (0.0333 mole) of iodine (Note 4). The resulting suspension is stirred and heated at reflux for 9 hours (Note 5), and then cooled to room temperature. The yellow precipitate of thallium(I) iodide is filtered and washed thoroughly with ethyl ether. The filtrates are comhined, the solvents are removed under reduced pressure with a rotary evaporator (Note 6), and the residual liquid is dissolved in dry ethyl ether. The turbid solution is dried with anhydrous potassium carbonate, and the solvent is again removed by rotary evaporation (Note 6), affording 5.4-6.3 g. of trans-1,2-cyclohexanediol diacetate as a mobile, brown liquid (Note 7). 

The diacetate is dissolved in 25 ml. of 95% ethanol, a solution of 2.9 g. (0.073 mole) of sodium hydroxide in 11ml. of water is added, and the resulting mixture is heated under reflux for 3 hours. The solution is concentrated by rotary evaporation under reduced pressure, and the remaining syrup is extracted with six 50-ml. portions of chloroform. The combined extracts are dried over anhydrous magnesium sulfate and evaporated, providing 3.1-3.3 g. of a pale brown crystalline solid that melts at 97-103°. Recrystallization from carbon tetrachloride gives 2.5-2.7 g. (65-70% based on iodine) of trans-1,2-cyclohexanediol, m.p. 103-104° (Note 8). 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

Cyclohexanediol diacetate, trans- (8,9) (1759-71-3) Thallixim(I) ethoxide Ethyl alcohol, thallium (1+) salt (8) Ethanol, thallium (1 + ) salt (9) (20398-06-5)... 

STEREOSELECTIVE HYDROXYLATION WITH THALLIUM(I) ACETATE AND IODINE trans- AND cis-l,2-CYCLOHEXANEDIOLS... 

Reaction of trans-1,2-cyclohexanediol with para-formaldehyde in the presence of Indion 130 as catalyst to yield the corresponding cyclic formal has been successfully carried out (Matkar and Sharma, 1995). A conversion of 52% was realized with 70% selectivity towards cyclohexanediol formal the other side products are rrans-hexahydrobenzo-l,3,5-trioxypin, di(tra i -2-hydroxycyclo-hexyloxy) methane. 

A third type of configurational interdependence exists if two elements are so interrelated that a change in the configuration of one automatically alters that of the other. This characterization applies to the two centers of 1,4-cyclohexanediol of the type Cg+g hi (5,51). Consequently only two isomers exist and a single pair of descriptors suffices for their distinction. We can remove the mutual dependence of the two elements by waiving the requirement that a line of stereoisomerism be occupied by bonds. The H and OH ligands have different distributions in the isomers about the line between C(l) and C(4), and the usual terms cis and trans express this relationship. Undoubtedly this is the most convenient description and the only one now available, but should we go further and say that the proper element of stereoisomerism in this case is this achiral line of torsion, and that its further factorization into two graphochiral centers is unwarranted ... 

The geometry of the cis-alkylcyclohexanol is favorable for trans elimination since the hydroxyl and the neighboring trans hydrogen are coplanar, but this is not true for the l,i-trans isomer hence the molecular conformation has to flip over, to set the hydroxyl group in the axial position for the trans elimination to occur. This would require a few kilocalories of energy and for frans-lert-butylcyclohexanol it would be more difficult to achieve than for IroMs-methylcyclohexanol. It is, therefore, possible that the trans elimination from a boat conformation, or possibly even an epimerization from the trans to the cis isomer which then undergoes a trans elimination reaction. Such an epimerization was found to occur under conditions of dehydration of certain alcohols over alumina, as will be seen under 1,4-cyclohexanediol. The more facile elimination of the cis-i-tert-butylcyclohexanol system as compared with the trans system in solution was also reported in the literature 63). 

The cis- and fmns-1,4-cyclohexanediols were dehydrated at about 250° over aluminas containing 0-2yo by weight of sodium ions, The trans isomer formed 1,4-epoxycyclohexane as the main product and... 

The rate of dehydration of the cis diol was about fifty times slower than that of the trans diol and the product of the reaction consisted mainly of cyclohexenol. The 1,4-epoxycyclohexane formed in the reaction was formed after a prior epimerization of the cis to the trans diol this was demonstrated by means of tritium tracer technique. When irons-1,4-cyclohexanediol was dissolved in ieri-butyl alcohol-T having the hydroxyl hydrogen marked with tritium (C4H,OT) the 1,4-epoxycyclohexane produced in this reaction had a very low tritium content. A similar reaction carried out with cis-1,4-cyclohexanediol produced a highly tritiated 1,4-epoxycyclohexane. The insertion of tritium in the 1,4-epoxycyclohexane produced from the cis diol can be explained as follows ... 

The type of anchimeric assistance encountered in the trans-1,4-cyclohexanediol dehydration had also been shown in solvolytic reactions of noncyclic diols (6, 70) and of 1,4-cyclohexanediol system 71). 

In order to explain the formation of nortricyclene from 2-ea o-norbornanol, it is necessary to assume a back side attack at the hydrogen attached to carbon 6. The general mechanism here is similar to the trans elimination reaction as discussed under menthol, 1,4-cyclohexanediol, and bornanols. 

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

For cyclic 1,2-diol-Cr(V) complexes, the multiplicity of the room-temperature CW-EPR signal depends upon the cyclic strain in the ligand.50 For these systems, the observed EPR hyperfrne pattern of the Cr(V)-diolate2 formed by reduction of Cr(VI) with GSH in the presence of c/.v-1.2-cyclohexanediol (6) or trans-1,2-cv c I oh e x an ed i ol... 

Because of the fact that, in [CrO(c/s-01,02-cyclohexanediolate)2] (situation as in Fig. 5, left), only one of the two carbinolic protons of each diol is in the Cr(V)-ligand plane, a triplet is observed in the room-temperature CW-EPR spectrum (two equivalent protons, Fig. 4B). On the other hand, the CrO(trans-01,02-cyclohexanediolate)21 species has both protons pointing above the Cr(V)-ligand plane (situation as in Fig. 5, right), and hence the CW-EPR spectrum shows no resolved hyperfine splitting (Fig. 4A). 

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