Fragmentation of Alcohols

The mle of the largest alkyl loss may be quantifiable. Zahorszky [4], studying fragmentation of alcohols and amines, showed that the peak intensities of [M — Alk,]+ ions may be calculated, as the ratio of intensities of these peaks is inversely proportional to the ratio of the masses of the corresponding ions. The intensities of the peaks of secondary ions should be added to the intensity of the corresponding primary ion peak. This mle is not applicable to the loss of methyl radical. 

Examples of cation-radical deprotonation-fragmentation of alcohols also deserve a separate consideration. Hammerum and Audier (1988) described the following reactions ... 

This example is important because carbon bond fragmentations occur at the first stages of the cation radical evolutions in cases of tert-butylated analogues of NADH (Fukuzumi et al. 1993). Scheme 6-48 describes this double-way fragmentation of the 9-tert-butyl-iV-methylacridan cation radical. Examples of the cation radical deprotonation-fragmentation of alcohols also deserve consideration. Hammerum and Audier described the reactions in 1988 ... 

Fragmentation of alcohols, ethers or amines usually leads to the cleavage of the C-C bond next to the heteroatom to generate a resonance-stabilised carbocation. This is known as a-cleavage. 

Scheme 2. Fragmentation of Alcohols. DIB = (diacetoxyiodo)benzene Ch indicates the rest of a cholestane molecule.

Lead tetraacetate calcium carbonate Fragmentation of alcohols s. 19, 342... 

The intensity of the molecular ion peak in the mass spectrum of a primary or secondary alcohol is usually rather low, and the molecular ion peak is often entirely absent in the mass spectrum of a tertiary alcohol. Common fragmentations of alcohols are a-cleavage adjacent to the hydroxyl group and dehydration. 

Fragmentation in the mass spectrometer favors formation of more stable cations. Thus fragmentation of alcohols gives resonance-stabilized hydroxycarbocations. 

Obtain five small dry test-tubes (75 x 10 mm. ) and introduce 1 ml. of the following alcohols into each ethyl alcohol, n-butyl alcohol, jcc.-butyl alcohol, cycZohexanol and butyl alcohol. Add a minute fragment of sodium to each and observe the rate of reaction. Arrange the alcohols in the order of decreasing reactivity towards sodium. 

Methyl ethyl ketone. Use the apparatus of Fig. Ill, 61, 1 but with a 500 ml. round-bottomed flask. Place 40 g. (50 ml.) of see. butyl alcohol, 100 ml. of water and a few fragments of porous porcelain in the flask. Dissolve 100 g. of sodium dichromate dihydrate in 125 ml. of water in a beaker and add very slowly and with constant sturing 80 ml. of concentrated sulphuric acid allow to cool, and transfer the resulting solution to the dropping funnel. Heat the flask on a wire gauze or in an air bath until the alcohol mixture commences to boil. Remove the flame and run in the dichromate solution slowly and at such a rate that the temperature... 

Fit a 750 ml. round-bottomed flask with a fractionating column attached to a condenser set for downward distillation. Place 500 g. of diacetone alcohol (the crude product is quite satisfactory), 01 g. of iodine and a few fragments of porous porcelain in the flask. Distil slowly. with a small free flame (best in an air bath) and collect the following fractions (a) 56-80° (acetone and a little mesityl oxide) (6) 80-126° (two layers, water and mesityl oxide) and (c) 126-131° (mesityl oxide). Whilst fraction (c) is distilling, separate the water from fraction (6), dry with anhydrous potassium carbonate or anhydrous magnesium sulphate, and fractionate from a small flask collect the mesityl oxide at 126-131°. The yield is about 400 g. 

Place 18 g. (12 ml.) of fuming nitric acid, sp. gr. 1 5, and 30 g. (16-5 ml.) of concentrated sulphuric acid and a few fragments of broken glass in a 250 or 500 ml. round-bottomed flask. Add gradually, in small portions, 14 g. of p-nitrotoluene do not allow the temperature to rise above 50 and cool the flask, if necessary, by immersion in cold water. Place a small funnel in the mouth of the flask and heat on a water bath at 90-95° for 30 minutes. Allow to cool almost to the laboratory temperature and pour the reaction mixture slowly into about 500 ml. of ice water containing a few small pieces of ice. Filter the crude dinitrotoluene through a Buchner funnel at the pump, wash it thoroughly with cold water, and drain as completely as possible. RecrystalUse from the minimum volume of hot methyl alcohol (flask, reflux condenser, and water bath experimental details as in Section IV,12). The yield of pure 2 4-dinitrotoluene, m.p. 71°, is 12 -5 g. 

Mix 31 g. (29-5 ml.) of benzyl alcohol (Section IV, 123 and Section IV,200) and 45 g. (43 ml.) of glacial acetic acid in a 500 ml. round-bottomed flask introduce 1 ml. of concentrated sulphuric acid and a few fragments of porous pot. Attach a reflux condenser to the flask and boil the mixture gently for 9 hours. Pour the reaction mixture into about 200 ml. of water contained in a separatory funnel, add 10 ml. of carbon tetrachloride (to eliminate emulsion formation owing to the slight difference in density of the ester and water, compare Methyl Benzoate, Section IV,176) and shake. Separate the lower layer (solution of benzyl acetate in carbon tetrachloride) and discard the upper aqueous layer. Return the lower layer to the funnel, and wash it successively with water, concentrated sodium bicarbonate solution (until effervescence ceases) and water. Dry over 5 g. of anhydrous magnesium sulphate, and distil under normal pressure (Fig. II, 13, 2) with the aid of an air bath (Fig. II, 5, 3). Collect the benzyl acetate a (colourless liquid) at 213-215°. The yield is 16 g. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Kcatf/o .—I. Dissolve a small quantity of benzil in a little alcohol, add a fragment of caustic potash and boil. A violet solution is obtained. 

The mass spectra of alcohols often completely lack a peak corresponding to the parent ion. This is due to extremely rapid loss of neutral fragments following initial ionization. For example, the mass spectrum of 2-methyl-2-butanol lacks a parent peak and contains strong peaks at M-15 (loss of CH3O and M-18 (loss of H2O). 

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

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