Primary alcohols chloride

It will also reduce acid chlorides, acid anhydrides and aldehydes to primary alcohols, ketones to secondary alcohols, and amides to the corresponding amines R-CONHi -> R CHiNH. Nitro-hydrocarbons if aromatic are... 

Aromatic primary alcohols diflfer from aliphatic primary alcohols in that they react with concentrated hydrochloric acid in the cold to yield the corresponding chlorides, for example ... 

If the temperature is not kept below 25°C dunng the reaction of primary alcohols with p toluenesulfonyl chloride in pyndine it is sometimes observed that the isolated product is not the desired alkyl p toluenesulfonate but is instead the corresponding alkyl chlonde Suggest a mech anistic explanation for this observation... 

Esters of nitro alcohols with primary alcohol groups can be prepared from the nitro alcohol and an organic acid, but nitro alcohols with secondary alcohol groups can be esterified only through the use of an acid chloride or anhydride. The nitrate esters of the nitro alcohols are obtained easily by treatment with nitric acid (qv). The resulting products have explosive properties but are not used commercially. 

Synthesis. Titanium alkoxy halides are intermediates in the preparation of alkoxides from a titanium tetrahaUde (except the fluoride) and an alcohol or phenol. If TiCl is heated with excess primary alcohol, only two chlorine atoms can be replaced and the product is dialkoxydichlorotitanium alcoholate, (RO)2TiCl2 ROH. The yields are poor, and some alcohols, such as aHyl, ben2yl, and /-butyl alcohols, are converted to chlorides (46). Using excess TiCl at 0°C, the trichloride ROTiCl is obtained nearly quantitatively, even from sec- and / f/-alcohols (47,48). 

BzCl or BZ2O, Pyr, 0°. Benzoyl chloride is the most common reagent for the introduction of the benzoate group. Reaction conditions vaiy depending on the nature of the alcohol to be protected. Cosolvents such as CH2CI2 are often used with pyridine. Benzoylation in a polyhydroxylated system is much more selective than acetylation. A primary alcohol is selectively... 

Secondary and primary alcohols do not react with HCl at rates fast enough to make the preparation of the conesponding alkyl chlorides a method of practical value. Therefore, the more reactive hydrogen halide HBr is used even then, elevated temperatures are required to increase the rate of reaction. 

Section 19.13 Among the reactions of carboxylic acids, their conversions to acyl chlorides, primary alcohols, and esters were introduced in earlier chapters and were reviewed in Table 19.5. 

Isobutylene, Amberlyst H-15, hexane. Methylene chloride can also be used as solvent, and in this case a primary alcohol was selectively converted to the /-amyl ether in the presence of a secondary alcohol. ... 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

A recently discovered (2) oxidizing system promises to become very important for the oxidation of acid-sensitive compounds. The reagent is chromium trioxide-pyridine complex, which may be isolated after preparation and employed in nonaqueous solvents (usually methylene chloride). A remarkable feature of the reagent is that good yields of aldehydes are obtained by direct oxidation of primary alcohols. The preparation of the reagent and its use are given. 

When a primary alcohol is treated with p-toluenesulfonyl chloride at room temperature in the presence of an organic base such as pyridine, a tosvlate is formed. When the same reaction is carried out at higher temperature, an alkyl chloride is often formed. Explain. 

Aldehydes and ketones are among the most important of ail compounds, both in biochemistry and in the chemical industry. AUdehydes are normally prepared in the laboratory by oxidation of primary alcohols or by partial reduction of esters. Ketones are similarly prepared by oxidation of secondary alcohols or by addition of diorganocopper reagents to acid chlorides. 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

Conversion of Acid Chlorides into Alcohols Reduction Acid chlorides are reduced by LiAJH4 to yield primary alcohols. The reaction is of little practical value, however, because the parent carboxylic acids are generally more readily available and can themselves be reduced by L1AIH4 to yield alcohols. Reduction occurs via a typical nucleophilic acyl substitution mechanism in which a hydride ion (H -) adds to the carbonyl group, yielding a tetrahedral intermediate that expels Cl-. The net effect is a substitution of -Cl by -H to yield an aldehyde, which is then immediately reduced by UAIH4 in a second step to yield the primary alcohol. 

The chemistry of acid anhydrides is similar to that of acid chlorides. Although anhydrides react more slowly than acid chlorides, the kinds of reactions the two groups undergo are the same. Thus, acid anhydrides react with water to form acids, with alcohols to form esters, with amines to form amides, and with UAIH4 to form primary alcohols. Only the ester and amide forming reactions are much used, however. 

The mechanism of ester (and lactone) reduction is similar to that of acid chloride reduction in that a hydride ion first adds to the carbonyl group, followed by elimination of alkoxide ion to yield an aldehyde. Further reduction of the aldehyde gives the primary alcohol. 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

To create a setting favorable for the formation of the E-ring of ginkgolide B, it is first necessary to modify the reactivity potential of ring F in 23. Exposure of a solution of 23 in methylene chloride to 1,3-propanedithiol and titanium(iv) chloride at 0°C results in the formation of dithiane 24 in quantitative yield. Oxidation of the primary alcohol with PDC in the presence of acetic acid gives aldehyde 25 in a yield of 75 %. 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

Finally, reaction of primary, secondary, or tertiary alcohols 11 with Me3SiCl 14 in the presence of equivalent amounts of DMSO leads via 789 and 790 to the chloro compounds 791 [13]. n-Pentanol, benzyl alcohol, yS-phenylefhanol or tert-butanol are readily converted, after 10 min reaction time, into their chloro compounds, in 89-95% yield, yet cyclohexanol affords after reflux for 4 h cyclohexyl chloride 784 in only 6% yield [13] (Scheme 6.5). 1,4-Butanediol is cyclized to tetrahydrofuran (THF) [13a], whereas other primary alcohols are converted in 90-95% yield into formaldehyde acetals on heating with TCS 14 and DMSO in benzene [13b] (cf also the preparation of formaldehyde di(n-butyl)acetal 1280 in Section 8.2.1). 

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