Preparation and properties of 3-alkyl-1-arylnitrosoureas and related compounds.

Abstract

Nitrosation of 3-alkyl-1-arylureas was investigated with sodium nitrite in 99% formic acid or with isoamyl nitrite in chloroform. The preparation of 3-alkyl-1-aryl-1-nitrosoureas was effectively performed by using isoamyl nitrite in the absence of acids, since the 1-nitrosoureas were isomerized to the 3-nitroso isomers by acids. The carbon-13 nuclear magnetic resonance and infrared spectral properties of the products were examined and their structural features are discussed.It was found that 3-alkyl-1-aryl-1-nitrosoureas decomposed to form alkyl isocyanates and 3-alky1-1-(2-nitroaryOureas in carbon tetrachloride. 1,3-Rearrangement and transnitrosation also took place in this solvent.We recently reported1) on the chemical properties of novel trisubstituted N-nitrosoureas. 3,3-Diethyl-1-(4-tolyl)-1-nitrosourea (1b) decomposed to give the triazene (2b) and the nitro compound (3) in chloroform or carbon tetrachloride at room temperature, while the 2-tolyl derivative (la) gave mainly the triazene (2a) under similar conditions. The reaction of nitrosoureas to give the triazenes is of interest because several derivatives of 3-alkyl-1 -phenyltriazenes and 3,3-dialkyl-1-phenyltriazenes have been reported to show antitumor activity.2) Therefore, we examined whether 3-alkyl-1-aryltriazenes were produced or not by the decomposition of 3-alkyl-1-arylnitrosoureas (4, 5).A number of reports have dealt with the antitumor activities and the chemical properties of 1,3-dialkylnitrosoureas.3-5) In a study of the nitrosation of 3-alkyl-1-phenylureas, Johnston et al.5) obtained a mixture of 1-nitrosoureas and the 3-nitroso isomers. Kamiya and co-workers6-8) described the synthesis and decomposition of 1,3-diaryl-1-nitrosoureas and related compounds. However, there are few data on the chemical properties of 3-alkyl-1-ary1-1-nitrosoureas, especially 3-methyl-l-phenyl-1-nitrosourea (4c), because of the difficulty of its isolation. In the nitrosation of 3-methyl-1 -phenylurea (9c), the 3-nitrosourea (6c) is produced overwhelmingly and the desired 1-nitrosourea (4c) can not be obtained by the ordinary method using sodium nitrite and acids. In this paper, we wish to present the preparation and properties of 3-alkyl-1-aryl-1-nitrosoureas and related compounds. Preparation of NitrosoureasN-Nitrosoureas (4 7) and N-nitrosoacetanilides (8) were prepared by nitrosation of the corresponding ureas (9, 10) and acetanilides, respectively. The ureas (9, 10) as starting materials were prepared by the reaction of aryl isocyanates with alkylamines or anilines with alkyl isocyanates in ether. Since the nitroso compounds were unstable at room temperature, they were quickly purified by silica gel column chromatography with a mixture of n-hexane and ether under cooling.1)The nitrosation of 1-aryl-1-isopropylureas (10) with sodium nitrite and 99% formic acid

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

“…Other secondary NH-containing systems have also been shown to undergo N -nitrosation. These include, in order of decreasing reporting frequency: amides, ureas, − carbamates, heteroamides, , hydroxylamines, , hydroxylamine ethers, hydrazines, , hydrazones, hydrazides, and guanidines. , In general, these systems are less used, and their reactivity is typically lower compared to secondary amines due to the weaker nucleophilic character of the NH moiety. Hydroxylamine- and hydrazine-type compounds are an exception as they are typically as nucleophilic as amines.…”

“…Besides the inherent lower reactivity of amides and related compounds toward the nitrosating species derived from aqueous HNO 2 ,acid-catalyzed hydrolysis can occur as a side reaction. Therefore, N -nitrosation of amides, sulfonamides, ureas, and carbamates have been alternatively carried out with sodium nitrite in neat organic acid such as acetic acid/acetic anhydride or formic acid (Scheme ).…”

A new family of urea-based low molecular-weight organogelators for environmental remediation: the influence of structure

“…Full details and figures are given in the ESI †. Molecules 1 , 3 and 6 appear to have been previously synthesized as reaction intermediates but not tested as LMWOs;31,32 and 2 , 4 and 5 were to the best of our knowledge, novel compounds.…”