Isopentyl Nitrite1

[110-46-3]  · C5H11NO2  · Isopentyl Nitrite  · (MW 117.17)

(oxidant and nitrosating agent;2 converts activated methylenes to oximes,3 alkyl4 and aryl5 primary amines to diazo compounds and diazonium salts, hydrazines to azides,6 2,6-disubstituted phenols to diphenoquinones,7 anthranilic acids to benzynes,8 aminophenols to quinone diazides,9 and phosphoramidates to phosphates10)

Alternate Name: amyl nitrite.

Physical Data: bp 99 °C; d 0.872 g cm-3.

Solubility: sol most nonhydrocarbon, organic solvents.

Form Supplied in: liquid; commercially available.

Handling, Storage, and Precautions: may be distilled prior to use. The material is a flammable, toxic liquid, which should be stored under nitrogen in a cool place. Use in a fume hood.

Nitrosation Reactions.

Isopentyl nitrite is a mild reagent for the introduction of the nitroso group. The nitrosations of aryl groups11 and p-excessive heterocyclic systems (eq 1)2,12 have been described. The nitrosation of alkenic carbons (eq 2)13 is known, as is the conversion of silyl ketene acetals to a-nitroso esters (eq 3).14 Isopentyl nitrite reacts with ureas, secondary amines, and amides to generate N-nitroso compounds.15 Tertiary amines having an a-silyloxy substituent have been converted by isopentyl nitrite to N-nitroso compounds in which the silyloxy methyl group has been cleaved (eq 4).16

Oxime Formation.

Nitroso groups on carbons bearing a-hydrogens normally tautomerize to the oxime. The conversion of a methylene group adjacent to a carbonyl-containing functionality to an oxime group is a general reaction of isopentyl nitrite.3,17-21 The reaction works well on acyclic17 and cyclic systems, with ring sizes of four (eq 5),18 five (eq 6),19 six,20 seven,3 and eight atoms21 having been described. As shown in eq 5, the anti-oxime is preferred to the syn-oxime in a-keto oximes of four-membered rings18 and this preference has been assumed in other ring sizes.19d,e In situ hydrolysis of a-keto oxime compounds has given a-diketones.20b,22 Other groups can also activate methylene and methyl groups toward oxidation with isopentyl nitrite. Methylene groups a to a nitrile functionality can form oximes with isopentyl nitrite (eq 7),23 as can methylene or methyl groups adjacent to aromatic or heteroaromatic rings (eq 8).24

Diazo and Diazonium Compounds.

Isopentyl nitrite is a preferred reagent for the conversion of aromatic or heteroaromatic amines to diazonium salts in polar organic solvents such as ethanol,25 isopropanol,26 acetic acid,27 acetonitrile,28 DMF,29 and acetone (eq 9).5 In other organic solvents, isopentyl nitrite and solvent react with the aromatic or heteroaromatic amine to give substitution products. Isopentyl nitrite in THF30 or dichloromethane31 converts the amino group to a hydrogen while isopentyl nitrite in benzene (or other aromatic solvents) gives phenyl substitution for the amine.32 Halogenated solvents such as diiodomethane33 or carbon tetrachloride34 react with isopentyl nitrite and the amine-containing substrate to give halogen substitution for the amine (eq 10). The use of dimethyl disulfide as a solvent with isopentyl nitrite gives methylthio substitution for the amine.35

Anthranilic acid8,36 and derivatives37 are converted to benzyne intermediates by isopentyl nitrite in organic solvents. Solvents such as glyme,8 dimethoxyethane,36a THF,36b,37a,b acetone,36c,37c and dioxane36d,e,37d have been employed in these reactions with good yields of benzyne cycloadducts with both 2p- and 4p-electron partners.

Aliphatic amines are also converted to alkane diazonium compounds with isopentyl nitrite in organic solvents.38 In THF,38a the overall reaction observed is substitution of hydrogen for the amine as was observed with aromatic and heteroaromatic amines. In acetic acid,38b,c acetate substitution for the amine is observed. In chloroform, intramolecular cyclization by attack of a secondary alcohol at the amine-bearing carbon has been observed.38d Isopentyl nitrite reacts with amines derived from acetylsilane O-silyl cyanohydrins to generate a-silyl ketones (eq 11).39

Diazo compounds are also generated from amines with isopentyl nitrite. a-Amino esters are converted to a-diazo esters with isopentyl nitrite and traces of an organic acid or water (eq 12).4,40 Both 1,2- and 1,4-aminophenols are converted to quinone diazides with isopentyl nitrite in the presence of trace amounts of acid (eq 13).9,41

Azide Formation.

Acyl azides (eq 14),6,42,43 which are important intermediates for the generation of peptide bonds and for the Curtius rearrangement,6,42 are formed from acyl hydrazines with isopentyl nitrite. This transformation is rapid in the presence of a variety of different functional groups. The acetylhydrazine derived from D-glucosamine has been converted to the corresponding azido sugar with isopentyl nitrite in aqueous THF.44

Phosphoramidate Cleavage.

The phosphoramidate group has been utilized to protect phospho monoesters.10,45 Part of the versatility of this particular protecting group is the facile cleavage of the P-N bond with isopentyl nitrite followed by treatment with pyridine to give an isolable monophosphate pyridinium salt.4,45

Other Reactions.

Isopentyl nitrite is one of several reagents that has been utilized for the coupling of 2,6-disubstituted phenols to give diphenoquinones (eq 15).7 In this particular procedure the coupling may occur via the dimerization of radical intermediates. Isopentyl nitrite has also been utilized in the hydrolysis of primary amides to carboxylic acids46 and in the hydrolysis to aldehydes and ketones of dithioacetals, which are resistant to both basic and acidic hydrolysis (eq 16).47

1. The chemistry of isopentyl nitrite has not been the specific subject of review.
2. Brothers, S. M.; McClelland, R. A. JOC 1987, 52, 1357.
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