Hydroxyl groups alkyl halides

Selectivity is not an issue m the conversion of alcohols to alkyl halides Except for certain limitations to be discussed m Section 8 15 the location of the halogen sub stituent m the product corresponds to that of the hydroxyl group m the starting alcohol... 

Alkylation (Section 25 22) Alkyl halides react with carbohydrates to form ethers at the available hydroxyl groups An application of the Williamson ether synthesis to carbohydrates... 

Pyrazoles, isoxazoles and isothiazoles with a hydroxyl group in the 3-position (491 Z = NR, O, S) could isomerize to 3-azolinones (492). However, these compounds behave as true hydroxy derivatives and show phenolic properties. They give an intense violet color with iron(III) chloride and form a salt (493) with sodium hydroxide which can be O-alkylated by alkyl halides (to give 494 R = alkyl) and acylated by acid chlorides (to give 494 R = acyl). 

The reaction was also found to be inhibited by addition of dioxan and tetra-hydropyran, the rate decrease being proportional to the ether concentration. The results were rationalised by the assumption that 2 1 and 1 1 phenol ether complexes were formed, respectively. The inhibition was attributed to participation of the hydroxyl group in solvation of the halogen atom of the alkyl halide, though this seems much less likely than a straightforward modification of the electron-supplying effect of the substituent3 54. 

Alkyl halides in the presence of silver oxide will convert any non-hindered carboxylic acid (or its salt) to the corresponding alkyl ester in minutes, and phenolic or thiol groups will also be alkylated rapidly [436]. Hydroxyl groups are alkylated slowly an ot always to completion. The alkyl halides most frequently uJQp are the lower molecular weight aliphatic... 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

Monocarbamoylation of diols is generally accomplished only with great difficulty. Reaction of the diol with an alkyl isocyanate is a possibility, but trimerization of the isocyanate frequently occurs [73]. The monocarbamic esters, which have PAF receptor antagonist activity, can be obtained however in acceptable yields via the phase-transfer catalysed in situ formation of the alkyl isocyanate from potassium isocyanate and an alkyl halide, and its subsequent reaction with the diol (see Scheme 3.8 for typical examples) [74], The diols tend to react more rapidly than do simple alcohols and m-diols are more effectively esterified that are /ra/rs-diols. Additionally, the longer the chain length between the hydroxyl centres, the less effective is the reaction. This has led to the reasonable hypothesis that a cyclic H-bonded intermediate between the two hydroxyl groups and the alkyl isocyanate are critical for the preferential and rapid formation of the carbamate. 

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

Katritzky et al. reported that alkyl halides convert to thiols in one pot when treated with a thiopyridine, which initially transforms to the pyridi-nium salt (34). Intramolecular ipsosubstitution takes place in the s t (34) by the remote hydroxyl group to afford the corresponding thiols shown in reaction (49) (85TL469). Thus, pyridinium sulfides readily undergo both... 

DMSO and /V, A- dime th y I fo nn a in i d c (DMF) are particularly effective in enhancing the reactivity of enolate ions, as Table 1.2 shows. Both of these compounds belong to the polar aprotic class of solvents. Other members of this class that are used as solvents in reactions between carbanions and alkyl halides include N-mcthyI pyrro I i donc (NMP) and hexamethylphosphoric triamide (HMPA). Polar aprotic solvents, as their name implies, are materials which have high dielectric constants but which lack hydroxyl groups or other... 

Hydroxyl Group. Reactions of the phenolic hydroxyl group include the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl halide (Williamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

The hydroxyl groups on glycols undergo the usual alcohol chemistry giving a wide variety of possible derivatives. Hydroxyls can be converted to aldehydes, alkyl halides, amides, amines, azides, carboxylic acids, ethers, mercaptans, nitrate esters, nitriles, nitrite esters, organic esters, peroxides, phosphate esters, and sulfate esters (6,7). 

The interaction of diaryl tellurides and the esters of halogenated fatty acids, e.g. methyl bromacetate, gives diarvl-telluretin halide alkyl esters, e.g. (C6H5)2Te(Br).CH2.COOCH3. The halogen present may be chlorine, bromine or iodine, moist silver oxide replacing the bromine by the hydroxyl group. 

Reaction LXXVIH. Action of Alkyl Halides on Alkali Alcoholates or Phenates. (P. R. S., 7, 135 J. C. S 2, 198 A., 78, 226 152, 164 B., 12, 116.)—This method is of importance as indicating the structure of ethers. It is applicable both in the aromatic and aliphatic series and can be used to obtain the ethers corresponding to the hypothetical di-and tri-hydric-alcohols, in which more than one hydroxyl group is attached to one carbon. 

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