Negative chemical ionization of alcohols.

Reactions of the oxygen radical anion at low pressure (ICR conditions) with aliphatic alcohols are seen to give a limited number of product anions which allows for unambiguous determination of the structure of the neutral. The reactions of OH- are also investigated and mechanisms of reactions are discussed. Analytical application of NCI is also considered. OH- negative chemical ionization mass spectra, negative metastable ion spectra, and negative collisional activation spectra (negative product from negative precursor ions) have been applied to stereochemical problems of cyclic diols. The spectra of the cis and trans isomers of 1,3- and 1,4-cyclohexanediols and 1,2- cyclopentanediols show substantial and characteristic differences. The (M-H)- alkoxide anions produced by OH- reagent ions are stabilized for the cis isomers by formation of an intramolecular hydrogen bridge involving both oxygen functions. However, trans geometry of the (M-H)- ions is indicated by abundant (M-H3)- and/or (M-H-H2O) fragment ions. The stereospecificity increases with ion internal energy (high temperature, collisional activation) or especially with ion life times (metastable ions). It is shown that in F- negative chemical ionization the relative intensities of the fluoride attachment ions MF- and of the proton abstraction ions (M-H)- reflect the stereochemistry of the cyclic diols. The results demonstrate the potential of negative ion mass spectrometry for stereochemical investigations.

Negative Chemical Ionization of Alcohols by R. Houriet,* D. Stahl,* and F. J. Winklert Reactions of the oxygen radical anion at low pressure (ICR conditions) with aliphatic alcohols are seen to give a limited number of product anions which allows for unambiguous determination of the structure of the neutral. The reactions of OHare also investigated and mechanisms of reactions are discussed. Analytical application of NCI is also considered.
OH-negative chemical ionization mass spectra, negative metastable ion spectra, and negative collisional activation spectra (negative product from negative precursor ions) have been applied to stereochemical problems of cyclic diols. The spectra of the cis and trans isomers of 1,3-and 1,4-cyclohexanediols and 1,2-cyclopentanediols show substantial and characteristic differences. The (M-H)alkoxide anions produced by OHreagent ions are stabilized for the cis isomers by formation of an intramolecular hydrogen bridge involving both oxygen functions. However, trans geometry of the (M-H)ions is indicated by abundant (M-H3)-and/or (M-H-H20) fragment ions. The stereospecificity increases with ion internal energy (high temperature, collisional activation) or especially with ion life times (metastable ions). It is shown that in F-negative chemical ionization the relative intensities of the fluoride attachment ions MF-and of the proton abstraction ions (M-H)reflect the stereochemistry of the cyclic diols. The results demonstrate the potential of negative ion mass spectrometry for stereochemical investigations.

ICR Study of the Negative Chemical Ionization of Alcohols
Negative chemical ionization (NCI) is a fast growing technique in the field of analytical mass spectrometry (1). In a recent publication by Smit and Field (2), the potential use of high pressure NCI in analytical chemistry has been demonstrated. In these studies, mixtures of N20 with various bath gases were used to generate the Oand OHreactant ions. The oxygen radical anion is easily formed by dissociative electron attachment to neutrals such as N20, 02, CO2, (1 The use of 0-(and consequently of OH-) as reactant ion is dictated by the relative ease of its formation from N2O and also because of its relatively high proton affinity [PA (0-) = 1594 kJ/ mole and PA (OH') = 1628 kJ/mole], thus resulting in efficient proton transfer reaction from most organic molecules. It was of interest to us that the 0and OHions react with alcohols to form a limited number of specific product anions (2). This is in contrast to the positive ion chemistry of alcohols in which most of the structural information related to the original molecule is lost in the course of either the unimolecular or the bimolecular reactions of ions derived from alcohols; typical examples will be briefly enumerated here.
In the positive ion mass spectra, the hydrocarbon ions predominate as the chain length increases, thus obscuring the typical alcohol fragmentation behavior (3). The intensity of the molecular ion is always low or not detectable in tertiary alcohols.
In positive ion CI conditions (4), the first reaction step is a proton transfer to the alcohol followed by rapid loss of a water molecule to form an alkyl ion. The decomposition reactions of the latter involves a substantial scrambling of the hydrogen and of the carbon atoms (5), in which the structural information on the original molecule is lost. Partial information on the structure of aliphatic alcohols may be obtained in more sophisticated CI experiments with protonated acetone and protonated acetaldehyde (6) or NO+ (7) as reagent ions.
In this work, we have used ion cyclotron resonance (ICR) to study the details of the reactions occurring between aliphatic alcohols and the ions present in the NCI conditions. ICR has been proven to be a powerful tool for simulating the high-pressure conditions (8,9); moreover, the use of double resonance techniques permits to identify the reaction sequences and product distribution resulting from the different reactant ions. A number of deuterated alcohols were also used.

Experimental
The ICR spectrometer used in this study was equipped with a four-section cell and marginal oscillator detection (5).
Formation of OH-. The hydroxylanion was formed from water by dissociative attachment of electrons accelerated at about 6.5 V (uncalibrated value), which in a first step produces H-that rapidly reacts with water (10), according to the reaction sequence (3): Formation of O -. The oxygen radical anion was formed from pure N2O under the conditions described above. It is known that under these conditions, 0is formed with an average 0.38 eV kinetic energy (11). In all experiments, the electrons were ejected from the reaction region of the ICR cell by applying a continuous radiofrequency of about 8MHz.

Results and Discussion
Reaction of OH-. The reaction of OHwith an aliphatic alcohol is known to consist of a proton transfer to the hydroxyl anion to form an alkoxide anion (12). When OHwas formed according to reaction (3) and made to react with alcohols (M), we found that in addition to the alkoxide anion product (M -1) -, a (M -3)-product was also formed. These results are reported in Table 1. From thermochemical data (13)(14)(15), it can be deduced that the loss of H2 from an alkoxide anion is a quite endothermic process (AHr = 35 -40 kJ/ mole). On the other hand, the proton affinities of alkoxide anions lie at 1560 + 5 kJ/mole. Therefore the formation of alkoxide anions by reaction of OH-with alcohols is exothermic by about 68 kJ/ mole. Part of this excess energy may be available to drive the endothermic loss of molecular hydrogen. The present results indicate that the (M -3) formation is quite a specific process involving the loss of one hydrogen atom from the a and one hydrogen atom from the fi position with respect to the hydroxyl group. Pressure and time dependence experiments now in progress indicate that the formation of (M -3)is a collisionally induced decomposition of the alkoxide anion according to reaction (4): Reaction of 0-. The reaction of 0with primary alcohols yields three types of ions (Table 2). Firstly OH-is formed in an abstraction reaction from the hydroxylic hydrogen atom: 0-+ C.H2.+20 --OH-+ C.H2+10 (5) The second reaction is a proton transfer reaction (6): 0-+ CnH2,+,OH -. C,^H2,+10-+ OH (6) The formation of the alkoxide anion involves the transfer of the hydroxylic proton to 0as indicated by the results of the labeling. Reaction Oreacts with secondary alcohols (Table 3)  The formation of the C^H2,_1Oproduct is not observed with the tertiary alcohols (Table 4) since no a hydrogen atom is available, but a large increase in the intenisity of lower homolog ions is observed.

Reaction Mechanism
The most striking difference in the reaction of 0with aliphatic alcohols as compared to the reaction of OH-, is the formation of fragment ions. Given the fact that the formation of the alkoxide anion is more exothermic by about 33 kJ/mole when OH-rather than Oreacts with the alcohol (13)(14)(15), these facts seem difficult to reconcile. An explanation is provided by the reaction mechanism proposed in the scheme shown as Eq. (7). The first step of the reaction consists of the addition of the reacting base to the hydroxylic group of the alcohol to form the addition complex I. Following an internal shift of a hydrogen atom which results in a significant gain in internal energy, the resulting intermediate II decomposes by losing a hydrogen atom (or an alkyl radical) and a water molecule to form the C.H2,_1O-(CkH?,O-) product (k < n). The overall reaction results in the elimination of the hydroxyl and the hydrogen atoms to form water and the loss of an a hydrogen atom (or an alkyl group), in accordance with our labeling experiments. On the other hand, when OHadds to alcohol to form the intermediate I' [Eq. (8) ] the latter can only lose a water molecule to form the alkoxide anion. Some limitations to this analytical approach can be foreseen, as for instance its inability to distinguish between, e.g., n-propyl and isopropyl groups. This work emphasizes the use of NCI as an analytical technqiue for a wide range of classes of organic compounds (1).

Stereochemical Effects on Anion Mass Spectra of Cyclic Diols
From the above section it is seen that gaseous alkoxide anions can provide conclusive mass spectrometric molecular weight and structural informations in the alcohol series.
In contrast to the importance of stereo-chemis-try in positive ion mass spectrometry (16)(17)(18), there are no detailed and systematic investigations on the stereochemistry of gas phase anions (19). This also applies to the class of cyclic alcohols, especially diols, which are model compounds of natural products. The observations of dimeric (M2-H)-alkoxide ions (20)(21)(22) indicated to us that stereochemical studies, based on intramolecular hydrogen bridge effects in diol mass spectra (23-28), might be extended from the cationic species MH+ and M+ to the anionic species (M-H) -. Gas phase anion techniques have been used to screen for stereochemical effects in the series of cyclohexane diols and related compounds.

Experimental
The spectra were recorded on a ZAB-2F double focusing, reverse geometry instrument equipped with a combination EI/CI source. A N20/CH4 mixture was used to generate OHreagent ions (2). The reagent gas pressure was 0.5 Torr. At -3% N2O in CH4, the optimum yield of OHwas was was was was obtained (70% OH-, 30% O). The diol spectra seemed to be insensitive to the Oreactant ions constantly present under our conditions. Negative collisional activation (NCA) spectra, corrected for negative metastable ion (NMI) contributions, were obtained at a helium pressure which reduced the precursor ion intensity to one third of its original value.
OH-Negative Chemical Ionization. The spectra of configurational isomers of cyclic diols show substantial and characteristic differences ( Table 5)    Environmental Health Perspectives  (25). In NCI, high ion source temperatures around 220°C are obviously more favorable for assignment of the diol configuration than lower temperatures, contrary to positive CI. Thus NCI seems to be promising for stereochemical analysis of natural products which show excessive fragmentation in positive CI spectra.
Negative Collisional Activation (NCA). The difference for the configurational isomers (Table  6) is increased strongly regarding the ratio for the (M-H3) -product peaks, even compared to the high temperature NCI spectra. Additional peaks with structural information also become more significant.
Negative Metastable Ion (NMI) Spectra. Metastable (M-H) -parent ions with little excess energy are highly sensitive to stereospecific reactions having low activation energy requirements. The intramolecular hydrogen bridge stabilization effect in the spectra of the cis isomers becomes maximized (Table 6).
F-Negative Chemical Ionization (NCI). Fluoride Freactant ions were produced by using CHF3 reagent gas. The reaction scheme for ROH substrates is: ROH + F-= ROH -* F-= RO-+ HF The gas phase proton affinities of F-(1548 kJ/ mole) and secondary alcoholate anions (e.g., Me2HCO-, 1565 kJ/mole) are nearly the same. Thus for the trans isomers of cyclic diols (Table  7), the base peak is formed by fluoride attachment ions, MF-. However, cis isomers with higher acidity due to intramolecular anion solvation, give (M-H) -proton abstraction ions as base peak. In this approach proton transfer equilibria are used to probe alcohol acidities related to the diol geometry. (In any of the dimeric M2Fions, independent of stereochemistry, intermolecular anion solvation supports proton transfer). These examples demonstrate the potential of negative ion mass spectrometry for the identification of stereoisomers. A larger variety of compounds has to be investigated to obtain more information about the analytical utility of stereochemical effects on anion mass spectra.