Hydroxyalkylation

Trimethylsilylation with trimethylchlorosilane affords the corresponding allene derivative, hydroxyalkylation with aldehydes and ketones gives mixtures of comparable amounts of acetylenic and allenic carbinols. 

Apparatus 4-1 flask (see Fig. 2) for the reaction with lithium amide 3-1 silvered Dewar flask, provided with a rubber stopper and a gas outlet for the hydroxyalkylation (no stirring was applied). 

The last group of reactions uses ring opening of carbonyl or 1-hydroxyalkyl substituted cyclopropanes, which operate as a -synthons. d -Synthons, e.g. hydroxide or halides, yield 1,4-disubstituted products (E. Wenkert, 1970 A). (1-Hydroxyalkyl)- and (1-haloalkyl)-cyclopropanes are rearranged to homoallylic halides, e.g. in Julia s method of terpene synthesis (M. Julia, 1961, 1974 S.F. Brady, I968 J.P. McCormick, 1975). 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

In a similar way, dl-2-(q-hydroxyalkyl)- and 2-(a-alkoxycarbonyl)-4-methyl-5-(/3-hydroxyethyl)thiazoles were synthetized from the corresponding thioamides and 4-hydroxy-3-bromo-2-pentanone (615). 

Hydroxyalkylthiazoles are also obtained by cyclization or from alkoxyalkyl-thiazoles by hydrolysis (36, 44, 45, 52, 55-57) and by lithium aluminium hydride reduction of the esters of thiazolecarboxylic acids (58-60) or of the thiazoleacetic adds. The Cannizzaro reaction of 4-thiazolealdehyde gives 4-(hydroxymethyl)-thiazole (53). The main reactions of hydroxyalkyl thiazoles are the synthesis of halogenated derivatives by the action of hydrobroraic acid (55, 61-63), thionyl chloride (44, 45, 63-66), phosphoryl chloride (52, 62, 67), phosphorus penta-chloride (58), tribromide (38, 68), esterification (58, 68-71), and elimination that leads to the alkenylthiazoles (49, 72). 

The hydroxyl groups can be alkylated in the usual manner. Hydroxyalkyl ethers may be prepared with alkylene oxides and chloromethyl ethers by reaction with formaldehyde and hydrogen chloride (86). The terminal chlorides can be easily converted to additional ether groups. 

Esters. Most acryhc acid is used in the form of its methyl, ethyl, and butyl esters. Specialty monomeric esters with a hydroxyl, amino, or other functional group are used to provide adhesion, latent cross-linking capabihty, or different solubihty characteristics. The principal routes to esters are direct esterification with alcohols in the presence of a strong acid catalyst such as sulfuric acid, a soluble sulfonic acid, or sulfonic acid resins addition to alkylene oxides to give hydroxyalkyl acryhc esters and addition to the double bond of olefins in the presence of strong acid catalyst (19,20) to give ethyl or secondary alkyl acrylates. 

Acrolein, acrylamide, hydroxyalkyl acrylates, and other functional derivatives can be more hazardous from a health standpoint than acryhc acid and its simple alkyl esters. Furthermore, some derivatives, such as the alkyl 2-chloroacrylates, are powerful vesicants and can cause serious eye injuries. Thus, although the hazards of acryhc acid and the normal alkyl acrylates are moderate and they can be handled safely with ordinary care to industrial hygiene, this should not be assumed to be the case for compounds with chemically different functional groups (see Industrial hygiene Plant safety Toxicology). 

Chiral glyoxylates have been used to effect of/z o-hydroxyalkylation of phenols via coordinative complexes. In this way, optically active 2-hydroxymandehc esters have been obtained with up to 94% diastereoselectivity (36). 

There is a wide variety of dyes unique to the field of hair coloring. Successive N-alkylation of the nitrophenylenediamines has an additive bathochromic effect on the visible absorption to the extent that violet-blue dyes can be formed. Since the simple A/-alkyl derivatives do not have good dyeing properties, patent activity has concentrated on the superior A/-hydroxyalkyl derivatives of nitrophenylenediamines (29,30), some of which have commercial use (31). Other substituents have been used (32). A series of patents also have been issued on substituted water-soluble azo and anthraquinone dyes bearing quaternary ammonium groups (33). 

HydroxyethyUiydrazine (11) is a plant growth regulator. It is also used to make a coccidiostat, furazoHdone, and has been proposed, as has (14), as a stabilizer in the polymerization of acrylonitrile (72,73). With excess epoxide, polysubstitution occurs and polyol chains can form to give poly(hydroxyaLkyl) hydrazines which have been patented for the preparation of cellular polyurethanes (74) and as corrosion inhibitors for hydrauHc fluids (qv) (75). DialkyUiydrazines, R2NNH2, and alkylene oxides form the very reactive amineimines (15) which react further with esters to yield aminimides (16) ... 

Ethyleneimine reacts with epoxides to form hydroxyaLkylated products, eg, A/-(P-hydroxyethyla2iridine) [1072-52-2]. The epoxide component is frequentiy used in substoichiometric amount in order to prevent multiple aLkoxylation (180—190). Ethyleneimine and episulftdes react to give complex product mixtures, since the l-(2-mercaptoethyl)a2iridine produced initially can easily react further with both reactants (191,192). 

Hydroxyalkyl acrylates and polyols are acetoacetylated with diketene to give comonomers used in adhesives, polymers, and coatings, especially the new low solvent coatings, and for emulsion polymeri2ation. The most widely used compound is 2-acetoacetoxyethyl methacrylate (A ARM A) (152). 

Substitution reactions on dialkyl peroxides without concurrent peroxide cleavage have been reported, eg, the nitration of dicumyl peroxide (44), and the chlorination of di-/ fZ-butyl peroxide (77). Bromination by nucleophilic displacement on a-chloro- or a-hydroxyalkyl peroxides with hydrogen bromide produces a-bromoalkyl peroxides (78). 

Hydroxyall l Hydroperoxides. These compounds, represented by (1, X = OH, R = H), may be isolated as discreet compounds only with certain stmctural restrictions, eg, that one or both of R and R are hydrogen, ie, they are derived from aldehydes, or that R or R contain electron-withdrawing substituents, ie, they are derived from ketones bearing a-halogen substituents. Other hydroxyalkyl hydroperoxides may exist in equihbrium mixtures of ketone and hydrogen peroxide. 

Hydroxyalkyl hydroperoxides from cycHc ketones (1), where X = OH, R =, H and R, R = alkylene, apparentiy exist in solution as equihbrium mixtures of the cycHc ketone, hydrogen peroxide, and other peroxides, eg, the dihydroperoxide (1) in which X = OOH, and dialkyl peroxides (2) where X = OH and Y = OH or OOH. Due to the existence of this equihbrium, the latter two dialkyl peroxides react as mixtures of monomeric hydroperoxides in solution. 

Hydroxyalkyl hydroperoxides having at least one a-hydrogen ie, (7, X = OH, R = alkyll, R = R = H), ie, those derived from aldehydes, lose hydrogen peroxide and form dialkyl peroxides (2, X = Y = OH), especially in the presence of water ... 

Acidic hydrolysis of these hydroxyaLkyl hydroperoxides yields carboxyUc acids, whereas basic hydrolysis regenerates the parent aldehyde, hydrogen peroxide, and often other products. When derived from either aldehydes or cycHc ketones, peroxides (1, X = OH, = H, R, = alkylene or... 

As with other hydroperoxides, hydroxyaLkyl hydroperoxides are decomposed by transition-metal ions in an electron-transfer process. This is tme even for those hydroxyaLkyl hydroperoxides that only exist in equiUbrium. For example, those hydroperoxides from cycHc ketones (R, R = alkylene) form an oxygen-centered radical initially which then undergoes ring-opening -scission forming an intermediate carboxyalkyl radical (124) ... 

Secondary alcohols, such as isopropyl alcohol, j -butyl alcohol, 2-pentanol, 3-pentanol, cyclopentanol, and cyclohexanol, have been autoxidized to hydroxyaLkyl hydroperoxides (1, X = OH R = H) (10,44). These autoxidations usually are carried out at ca 20°C with uv radiation in the presence of a photosensitizer, eg, benzophenone. a-Oxygen-substituted dialkyl peroxides (2, X = Y = OH and X = Y = OOH), also are formed and sometimes they are the exclusive products (10). 

Hydroxyalkyl Alkyl Peroxides and Hydroxyalkyl Peroxyesters. The same stmctural restrictions discussed for the hydroxyhydroperoxides apply for the hydroxyalkyl alkyl peroxides, and those that exist are derived from aldehydes and certain ketones having electron-withdrawing groups, eg, polyfluorinated a,P-unsaturated ketones (136). 

Table 6. Boiling Points of Some Hydroxyalkyl Alkyl Peroxides ...

Hydroxyalkyl peroxyesters also have been isolated from the autoxidation products of aldehydes and by esterification of hydroxyhydroperoxides (44). 

Mesityl oxide and hydrogen peroxide react initially to form the cycHc hydroxyalkyl alkyl peroxide, a 1,2-dioxolane. Prolonged equiUbration results in formation of the cycHc di(alkylperoxyalkyl) peroxide, 3,3 -dioxybis(3,5,5-trimethyl-l,2-dioxolane) [4507-98-6] (122,138) ... 

In the presence of strong acid catalysts such as sulfuric acid, aUphatic (R CHO) aldehydes react with alkyl hydroperoxides, eg, tert-55ky hydroperoxides, to form hydroxyalkyl alkyl peroxides (1), where X = OH R, = hydrogen, alkyl and = tert — alkyl. 

Geminal Dihydroperoxides. These dihydroperoxides (1, X = OOH, R = H) can be made from many different carbonyl compounds. The stmctural restrictions discussed for hydroxyalkyl hydroperoxides generally do not apply. These peroxides can also be synthesi2ed by perhydrolysis of ketals (143). 

Di(hydroxyall l) Peroxides. The lowest molecular weight member of this group (2, X = Y = OH), di(hydroxymethyl) peroxide (R = R = OH) is a dangerously explosive soHd. With increasing molecular weight, di(hydroxyalkyl) peroxides become Hquids and eventually soHds of... 

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