Hydroxylation of aliphatic compounds

The microbial hydroxylation of aliphatic compounds can effect the functionalization of molecules at positions distant from pre-existing groups. Such functionalizaton of non-activated positions is difficult to emulate using conventional chemistry. A good deal of research in this area has con-... 

Hydroxylation of aliphatic compounds, e.g. pentobarbital, antipyrine, tolbutamide, imipramine. 

Frommer U, Ullrich V, Staudinger H (1970) Hydroxylation of aliphatic compounds by liver micro-... 

The hydroxylation of C-H bonds by radicals, in contrast to the case of electrophilic oxidants, leads to alcohols without retention of stereochemical configuration. H202, activated by strong acids (superacids (277), HF-BF3 (272), A1C13 (213), and CF3COOH (214)) have been used for the hydroxylation of aromatic compounds. These acid-catalyzed hydroxylations cannot be applied for aliphatic reactants because the hydroxylated products are more reactive than the starting compounds and, hence, they are oxidized further. 

Anbar M, Meyerstein D, Neta P (1966b) Reactivity of aliphatic compounds towards hydroxyl radicals. J Chem Soc Perkin Trans 2 742-747... 

Al-Sheikhly Ml, Schuchmann H-P, von Sonntag C (1985) y-Radiolysis of N20-saturated formate solutions. A chain reaction. Int J Radiat Biol 47 457-462 An bar M, Meyerstein D (1964) Isotope effects in the hydrogen abstraction from aliphatic compounds by radiolytically produced hydrogen atoms in aqueous solutions. J Phys Chem 68 3184-3167 Anbar M, Meyerstein D, Neta P (1966) Reactivity of aliphatic compounds towards hydroxyl radicals. J Chem Soc Perkin Trans 2 742-747... 

Cytochrome P450 (P450) enzymes are heme-containing monooxygenases found in Bacteria, Archaea and Eukarya that catalyze hydroxylations of aliphatic and aromatic compounds ( RH ) according to the overall reaction " ... 

The introduction of a hydroxy group in an aliphatic compound already containing a simple oxygen function, such as an ether, does not affect the oxidation potential significantly. Consequently, the products of anodic hydroxylation of aliphatic ethers may survive the conditions necessary for the oxidation of substrate. For example, tetrahydrofuran has successfully been converted to 2-hydroxytetrahydrofuran by anodic oxidation in 1 M H2SO4 at Pt, as in Eq. (15) [29]. However, the hydroxylation of diisoalkyl ethers results in highly oxidized products such as ketones and acids [30]. 

C02 band shows a concentration in the center of the inclusion. The contour plots for the 3697 cm 1 hydroxyl band and for the integrated intensity under the set of absorption bands between 3000-2800 cm 1 are very similar with higher concentration towards the outer edges of the inclusion. The authors conclude that the center of the inclusion is in a vapor phase that consists mostly of C02 under high pressure. In addition, the authors deduce that the surrounding material is in a liquid phase, and consists of aliphatic compounds terminated by hydroxyls. These results should motivate further studies to identify and understand the chemical nature of compounds inside inclusions. 

Halogen derivatives of aromatic compounds may also be prepared from hydroxyl derivatives by a reaction which is analogous to that used in the case of aliphatic compounds. When phenol, CeHsOH, and similar substances are treated with the halides of phosphorus, the hydroxyl groups are replaced by halogen. The yield of halogen compound is small in most cases, however, and the reaction is seldom used as a means of preparing such compounds. When the hydroxyl group is situated in a side-chain, the reaction takes place, in the main, as in the case of aliphatic compounds. 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reactions, classically referred to as phases one and two. Phase I is a functionalization of the lipophilic compound that can be used to attach a conjugate in Phase II. The conjugated product is usually sufficiently water-soluble to be excretable into the urine. The most important biotransformations of Phase I are aromatic and aliphatic hydroxylations catalyzed by cytochromes P450. Other Phase I enzymes are for example epoxide hydrolases or carboxylesterases. Typical Phase II enzymes are UDP-glucuronosyltrans-ferases, sulfotransferases, N-acetyltransferases and methyltransferases e.g. thiopurin S-methyltransferase. 

The reactions of the six-membered chlorocyclophosphazene were studied with a number of aliphatic diamines (169 175), aromatic diamines (176), aliphatic diols (177-179), aromatic diols (180,181) and compounds containing amino and hydroxyl functional groups (169,170,182). This subject has been reviewed (11,16,20). There are at least five different reaction products that are possible (Fig. 19). Replacement of two chlorine atoms from the same phosphorus atom produces a spirocyclic product. Replacement of two chlorine atoms from two different phosphorus atoms in the same molecule produces an ansa product. Reaction of only one end of the difunctional reagent, resulting in the substitution of only one chlorine atom, leads to an open-chain compound. Intermolecular bridged compounds are formed when the difunc-... 

This initial attack of the ozone molecule leads first to the formation of ortho- and para-hydroxylated by-products. These hydroxylated compounds are highly susceptible to further ozonation. The compounds lead to the formation of quinoid and, due to the opening of the aromatic cycle, to the formation of aliphatic products with carbonyl and carboxyl functions. The nucleophilic reaction is found locally on molecular sites showing an electronic deficit and, more frequently, on carbons carrying electron acceptor groups. In summary, the molecular ozone reactions are extremely selective and limited to unsaturated aromatic and aliphatic compounds as well as to specific functional groups. 

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