Ortho-hydroxy aromatic

A few mg of the steroids in a reaction vial are treated with 20 fi of a hexane solution containing 2% DMDAS and 2% triethylamine for 2 h at 40 °C, and the products are analysed directly [37]. A similar procedure, on the micro scale, may be used for salicylic and anthranilic acids and other ortho-hydroxy aromatic adds (40). 

AUen, N. S., Photostabihzing action of ortho-hydroxy aromatic compounds a critical review, Polym. Photochem., 3,167,1983. 

The formylation of a phenol 1 with chloroform in alkaline solution is called the Reimer-Tiemann reaction. It leads preferentially to formation of an ortho-formylated phenol—e.g. salicylic aldehyde 2 —while with other formylation reactions, e.g. the Gattermann reaction, the corresponding /jara-formyl derivative is obtained as a major product. The Reimer-Tiemann reaction is mainly used for the synthesis of o-hydroxy aromatic aldehydes. 

Sections D through H of Scheme 3.2 involve oxygen nucleophiles. The hydrolysis reactions in Entries 12 and 13 both involve benzylic positions. The reaction site in Entry 13 is further activated by the ERG substituents on the ring. Entries 14 to 17 are examples of base-catalyzed ether formation. The selectivity of the reaction in Entry 17 for the meta-hydroxy group is an example of a fairly common observation in aromatic systems. The ortho-hydroxy group is more acidic and probably also stabilized by chelation, making it less reactive. 

Good non-colored negative charging CCAs have been obtained by making non-colored analogues of the 2 1 chromium complex azo dyes. This is achieved by making the metal complex of an aromatic ortho-hydroxy carboxylic acid. Typical examples are the chromium, aluminum, and zinc complexes of di-tert-butyl salicylic acid, e.g., BONTRON E-8136 41 (53) and BON-acid36,41,42 e.g., BONTRON E-82 (54). 

The oxidative cyclization of an ortho-hydroxy-methoxy-substituted aromatic system giving a methylenedioxy group is also known to involve a cytochrome P-450-dependent mono-oxygenase. This enzyme hydroxylates the methyl to yield a formaldehyde hemiacetal intermediate, which can cyclize to the methylenedioxy bridge (the acetal of formaldehyde) by an ionic mechanism (Figure 2.21). 

Lajunen, L.H.J. Portanova, R. Piispanen, J. Tolazzi, M. Critical evaluation of stability constants for alpha-hydroxycarboxylic acid complexes with protons and metal ions and the accompanying enthalpy changes. Part I. Aromatic ortho-hydroxy carboxylic acid. PureAppl. Chem. 1997, 69 (2), 329-381. 

Phosphorylated ketenes react with aromatic ortho -hydroxy aldehydes to form coumarins by the Wittig -Horner - type reaction. 

High anti-diastereoselectivity is observed for several aromatic imines for ortho-substituted aromatic imines the two newly formed stereocenters are created with almost absolute stereocontrol. Aliphatic imines can also be used as substrates and the reaction is readily performed on the gram scale with as little as 0.25 mol% catalyst loading. Furthermore, the Mannich adducts are readily transformed to protected a-hydroxy-/8-amino acids in high yield. The absolute stereochemistry of the Mannich adducts revealed that Et2Zn-linked complex 3 affords Mannich and aldol adducts with the same absolute configuration (2 R). However, the diastereoselectiv-ity of the amino alcohol derivatives is anti, which is opposite to the syn-l,2-diol aldol products. Hence, the electrophiles approach the re face of the zinc enolate in the Mannich reactions and the si face in the aldol reactions. The anti selectivity is... 

A new method for the ortho hydroxylation of aromatic aldehydes via orrho-lithiated arcnnatic aminoal-koxides has recently been reported by Einhom et al Fonnation of the aminoalkoxide serves two purposes. Firstly, the aldehyde group is protected and, secondly, the aminoalkoxide directs lithiation to the ortho position. Oxidation of the lithio species was effected by either MoOPH or molecular oxygen, albeit in poor yield. Alternatively, a two-step, one-pot condensation of the lithio intermediate with tributyl borate followed by oxidation with hydrogen peroxide gave the ortho-hydroxy aldehydes (24) in slightly better yields (Scheme 9). 

Sodium borohydride in methanol/dichloromethane (1 1) at-78 °C reduced ketones in the presence of conjugated enones with excellent selectivity. Competition experiments were complemented by reductions of diones to illustrate the synthetic value of the method. The Wieland-Miescher ketone was reduced to the 1-p-alcohol contaminated by less than 3% diol in quantitative yield. The same reagent in acetic acid was shown to be effective at reducing aromatic ketones with ortho hydroxy or ortho amino substituents rapidly.Other aromatic ketones were relatively inert under the same conditions. Presumably the success of this procedure relies on activation and intramolecular delivery of the acetoxyborohy-dride by the ortho substituent. 

Hydroxylations of aromatic rings are also achieved via transient esters that are easily hydrolyzed in situ to the corresponding phenols. In this way, anisole and diphenyl ether are oxidized by peroxytrifluoroacetic acid to predominantly ortho-hydroxy compounds in low yields (equation 147) [1118]. 

V. N. Komissarov, V A. Kharlanov, L. Yu. Ukhin, E. Yu. Bulgarevich, and VI. Minkin, Photo-and thermochromic Mannich bases. Derivatives of 2,6-di-fert-butylphenol and aromatic ortho-hydroxy aldehydes, Zh. Org. Khim. 28,513-517 (1992). 

In the case of ortho-hydroxy Mannich bases, no such possibility exists. Hence, in the ortho-hydroxy Mannich and Schiff bases (Scheme 1) the energetics and TT-electron delocalization may differ significantly as well as geometry of the quasi-ring built of the H-bonded OCCCN chain. The changes in geometry may also be observed in the aromatic ring. 

It means that the increase of stabilization of chelate chain is associated with a decrease of aromaticity, i.e., Tr-electron delocalization in the ring. A similar situation was observed for the first X-ray determined ionic H-bonding in the crystal state for ortho-hydroxy Schiff base—5-nitro-A-salicylideneethylamine... 

Compared to the chemical synthesis of ortho-substituted catechols (ortho-hydroxy-lation and aromatization procedures) 28 31 such an enzymatic approach is superior with respect to the number of steps involved as well as simplicity, selectivity, and yield. The resulting ortho-substituted catechols are valuable building blocks[32i. 

Graphite combined with methanesulfonic acid represents an effective catalyst for the acylation of phenols and naphthols, wifh carboxylic acids giving a good yield of ortho-hydroxy aryl ketones (Table 5.4). The reactions seem to be faster with activated aromatic carboxylic acids. It must be emphasized that, in the absence of graphite, in the model reaction between mefa-cresol and BAC, the product is isolated in lower yield (20% versus 81%). 

Acetophenone is converted in this way into the diethylene ketal in 74% yield. Under the same conditions benzophenone is unreactive. The reagent appears particularly useful for preparation of acetals of aromatic ortho-hydroxy aldehydes. Ketalization of A -3-keto steroids is accompanied by migration of the double bond [(1) (2)]. The tetrathio orthocarbonate (3) can be used in the... 

The simplest synthesis of coumarins is a special case of the Perkin condensation i.e. the condensation of an aromatic aldehyde with an anhydride. ortho-Hydroxy-trans-cinnamic acids cannot be intermediates since they do not isomerise under the conditions of the reaction nor can O-acetylsalicylaldehyde be the immediate precursor of the coumarin, since it is not cyclised by sodium acetate on its own. ... 

Some special derivatization methods that lead to the formation of cyclic products were recommended for alcohols with more than two hydroxyl groups in the molecule (polyols including carbohydrates), amino alcohols, and polyfunctional aromatic hydroxy compounds. An appropriate arrangement of two functional groups [(OH)2, (OH) + (NH2) or (OH) + (CO2H)] in 1,2 (vie) 1,3 or ortho (in aromatic series) positions is necessary for their realization (Table 8). 

The nuclear magnetic resonance spectra of SchifF bases formed from primary amines and ortAo-hydroxy aldehydes and ketones show that the Schiff bases derived from l-hydroxy-2-acetonaphthone and from 2-hydroxy-1-naphthaldehyde exist as keto amines (7a) although their formation involves loss of most of the resonance energy of one of the aromatic rings When R is a phenyl group, the phenol-imine tautomer (7b) predominates Schiff bases derived from ortho-hydroxy aldehydes and ketones have the phenol-imine structure (8) . Evidently, in such compounds the keto-amine tautomer... 

The reactive group involved on the hydroxy-aromatic compound is not the hydroxy group itself but the carbon atoms on the ortho (2,6) and para (4) positions relative to the hydroxy group (attached to carbon atom 1). Unsubstituted phenol can therefore react with formaldehyde from three different positions independently, so should be regarded as a three-functional monomer. If the phenol derivatives have substituents on the ortho and/or para positions, their functionality is decreased accordingly. For example (see Scheme 16.1), cresol (methylphenol) is two-functional when the methyl group is in the 2 or 4 position relative to OH (o-cresol and p-cresol, respectively) but three-fimctional when in the 3 position (m-cresol). Further, commonly used two-functional substituted phenol derivatives are p-tert-butylphenol and p-tert-nonylphenol. The aliphatic groups on these monomers decrease the solubility of the resins in water but increase the solubility (compatibility) of these resins with more hydrophobic solvents (hydrocarbons) and resins. 

C-alkylation of secondary and tertiary aromatic amines by hexafluoroacetone or methyl trifluoropyruvate is performed under mild conditions [172] (equation 147) The reaction of phenylhydrazme with hexafluoroacetone leads selectively to the product of the C-hydroxyalkylation at the ortho position of the aromatic ring The change from the para orientation characteristic for anilines is apparently a consequence of a cyclic transition state arising from the initial N hydroxy alky lation at the primary amino group [173] (equation 148)... 

The Dakin reaction proceeds by a mechanism analogous to that of the Baeyer-Villiger reaction. An aromatic aldehyde or ketone that is activated by a hydroxy group in the ortho or para position, e.g. salicylic aldehyde 12 (2-hydroxybenzaldehyde), reacts with hydroperoxides or alkaline hydrogen peroxide. Upon hydrolysis of the rearrangement product 13 a dihydroxybenzene, e.g. catechol 14, is obtained ... 

Treatment of a mixture of ortho anisidine and bis(2-hydroxy-ethyl) amine with hydrogen chloride affords the aryl-substituted piperazine, 171. (The first step in this reaction probably consists in conversion of at least one hydroxyl group to the chloride this then serves to alkylate the aromatic amine.) Alkyla-... 

Compounds which correspond to 1,2-quinone diazides can also be obtained by diazotization of aromatic and nonaromatic heterocyclic amines with a hydroxy group in the ortho position. Examples include 3,4-quinolinequinone-3-diazide (2.35, Sus et al., 1953 Sus and Moller, 1955) and 3-diazochromane-2,4-dione (2.36, Arndt et al., 1951). Syntheses of more complex heterocyclic quinone diazides have been tabulated by Ershov et al. (1981, p. 105). More recent publications are cited in a paper by Tisler s group (Klotzer et al., 1984). 

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