Alcohol structure determination

An example of how information from fragmentation patterns can be used to solve structural problems is given in Worked Example 12.1. This example is a simple one, but the principles used are broadly applicable for organic structure determination by mass spectrometry. We ll see in the next section and in later chapters that specific functional groups, such as alcohols, ketones, aldehydes, and amines, show specific kinds of mass spectral fragmentations that can be interpreted to provide structural information. 

Glycine receptor function is modulated by alcohols and anesthetics [4]. Amino acid residue al(S267) is critical for alcohol potentiation, as mutation to small residues (Gly, Ala) enhance, and mutation to large residues (His, Cys, Tyr) diminish the ethanol effect. Glycine recqrtor modulation by Zn2+ involves structural determinants located within the large N-terminal domain. Additional glycinergic modulators include neuroactive steroids and the anthelmintic, ivermectin, which activates glycine receptors by a novel, strychnine-insensitive mechanism. 

The late stages of the synthesis (Scheme 1.17) proceeded with Wittig methylenation of ketone 144 with Ph3P=CH2 at 70 °C to furnish exocyclic alkene 145 in 77 % yield. Finally, the alcohol was installed via a Se02-mediated allylic hydroxylation [57] of the exocyclic alkene 145 to afford ( )-nominine (1) in 66 % and 7 1 dr. The structure of nominine (1) was verified via an X-ray crystal structure determination, thereby completing the racemic total synthesis of ( )-nominine (1). 

The reaction of 3,4-bis(benzenesulfonyl)furoxan with alcohols and thiols in basic media affords a variety of alkoxy-and alkylthio-substituted (benzenesulfonyl)furoxans. For these derivatives a paramount problem is to determine the position (3- or 4-) of the substitution in the furoxan ring. The structures of these derivatives were assigned on the basis of both chemical and NMR evidence. In particular, 13C NMR substituent constants were obtained by NMR study of suitable furoxan models. By assuming a complete additivity of the substituent effects at the furoxan ring, these values were used for structural determination <1997FES405>. 

Obviously, the first intermediates in the syntheses with terminal alkynols are the vinylidene complexes [Ru(bdmpza)Cl(=C= CH(CH2) +iOH)(PPhg)] (n = 1, 2), which then react further via an intramolecular addition of the alcohol functionality to the a-carbon (Scheme 22), although in none of our experiments we were able to observe or isolate any intermediate vinylidene complexes. The subsequent intramolecular ring closure provides the cyclic carbene complexes with a five-membered ring in case of the reaction with but-3-yn-l-ol and with a six-membered ring in case of pent-4-yn-l-ol. For both products type A and type B isomers 35a-I/35a-II and 35b-I/ 35b-II are observed (Scheme 22, Fig. 22). The molecular structure shows a type A isomer 35b-I with the carbene ligand and the triphenylphosphine ligand in the two trans positions to the pyrazoles and was obtained from an X-ray structure determination (Fig. 25). 

The zero slope found for transesterification (series 45) can be explained in accordance with the general view on acid-catalyzed reactions of organic acids and esters. The first step is the protonation of the acid or ester, which is followed by interaction with the alcohol (or water in ester hydrolysis). The absence of any observable influence of the alcohol structure on rate indicates that the rate-determining step must be the protonation of the ester. This is in contrast to the homogeneous reaction, in which this step is usually very rapid. The parallel dehydration of the alcohols exhibited a large structure effect on rate (Case 7 from Table II), confirming the independence of the two reaction routes. 

Heavy-atom derivation of an object as large as a ribosomal particle requires the use of extremely dense and ultraheavy compounds. Examples of such compounds are a) tetrakis(acetoxy-mercuri)methane (TAMM) which was the key heavy atom derivative in the structure determination of nucleosomes and the membrane reaction center and b) an undecagold cluster in which the gold core has a diameter of 8.2 A (Fig. 14 and in and ). Several variations of this cluster, modified with different ligands, have been prepared The cluster compounds, in which all the moieties R (Fig. 14) are amine or alcohol, are soluble in the crystallization solution of SOS subunits from H. marismortui. Thus, they could be used for soaking. Crystallographic data (to 18 A resolution) show isomorphous unit cell constants with observable differences in the intensity (Fig. 15). 

Alcohols. These yield suitable derivatives by ester or carbamate formation. (—)-(l ,4/ )-Cam-phanoyl chloride is an especially useful reagent15 7, as demonstrated by the following examples. The absolute configuration of the isoprene iron tricarbonyl complex 6 was determined from the X-ray structure determination of (1R,45)-camphanoate 4, the precursor of 6158. 

Terpenes are characterized as being made up of units of isoprene in a head-to-tail orientation. This isoprene concept, invented to aid in the structure determination of terpenes found in natural products, was especially useful for elucidation of structures of more complex sesquiterpenes, diterpenes, and polyterpenes. The hydrocarbon, myrcene, and the terpene alcohol, OC-terpineol, can be considered as being made up of two isoprene units in such a head-to-tail orientation (1). 

As mentioned above, a variety of complexes of type (10) can easily be prepared by alcohol exchange and, in this way, compounds with R = Pr", Bun, Pen , Oct" have been isolated and characterized.221 However, when secondary alcohols have been used for exchange with (10), mixed alkoxy species were obtained. NMR showed that the bridging ethoxide ligands had not been replaced, a result that was confirmed by the crystal structure determination of the mixed ethoxide-isopropoxide and ethoxide-sec-pentoxide derivatives. 

In molecular crystals held together by ionic forces (for instance, salts of organic acids) or polar forces such as hydrogen bonds (for instance, alcohols and amides), the two influences, shape and distribution of forces, may not co-operate, and it is difficult to form any definite conclusions on the structure from crystal shape and cleavage, though it is well to keep these properties in mind during structure determination, for any suggested structure should account for them. 

Carbohydrates undergo chemical reactions characteristic of aldehydes and ketones, alcohols, diols, and other classes of compounds, depending on their structure. A review of the reactions described in this chapter is presented in Table 25.2. Although some of the reactions have synthetic value, many of them are used in analysis and structure determination. 

Exercise 15-15 How can D-glucose, D-fructose, and D-ribose be considered products of the addition of an alcohol to the carbonyl group of an aldehyde or ketone Name each of the carbonyl compounds by the IUPAC system. For the ribose carbonyl structure, determine the configuration at each chiral center, using the D,L system. 

A number of derivatives of the tartaric acid structure have been examined as substitutes for the tartrate ester in the asymmetric epoxidation catalyst. These derivatives have included a variety of tartramides, some of which are effective in catalyzing asymmetric epoxidation (although none display the broad consistency of results typical of the esters). One notable example is the dibenzyltartramide, which in a 1 1 ratio (in reality, a 2 2 complex as shown by an X-ray crystallographic structure determination [138]) with Ti(0-i-Pr)4 catalyzes the epoxidation of allylic alcohols with the same enantiofacial selectivity as does the Ti-tartrate ester complex [18], It is remarkable that, when the ratio of dibenzyltartramide to Ti is changed to 1 2, epoxidation is catalyzed with reversed enantiofacial selectivity. These results are illustrated for the epoxidation of a-phenylcinnamyl alcohol (Eq. 6A.12a). 

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