Nitrosoamide

Other methods of converting amides to esters have been described (78). Alkyl haUdes can be treated with amides to give esters (79). Also, esters can be synthesized from A/-aIkyl-A/-nitrosoamides, which are derived from the corresponding amides (80). 

Reaction of metal hydride complexes with N-nitrosoamides, e.g. Af-methyl-7V-nitrosourea ... 

DEAMINATION OF AMINES. 2-PHENYLETHYL BENZOATE VIA THE NITROSOAMIDE DECOMPOSITION... 

If the nitroso derivative is desired, the yellow solid is separated by filtration, washed with water, 5% sodium bicarbonate solution, water, and dried under reduced pressure at room temperature. The solid is recrystallized from ether to give yellow needles of pure nitrosoamide yield 7.5 g. (64%), m.p. 57-58° (dec.). 

C. 2-Phenylethyl benzoate. The carbon tetrachloride solution of N-nitroso-N-(2-phenylethyl)benzamide (Note 4) and 0.1 g. of sodium carbonate (Note 5) are placed in a 200-mi. round-bottomed flask equipped with a condenser, and the mixture is heated under reflux for 24 hours. The evolution of nitrogen ceases, and the yellow color of the nitrosoamide disappears near the end of this period. The solution is washed with 5% sodium hydroxide solution, water, and dried. The solvent is removed under reduced pressure and the 2-phenylethyl benzoate distilled b.p. 138-142° (1 mm.), yield 5.8-6.1 g. [56-59% based on N-(2-phenylethyl) benzamide]. 

In general, the nitrosoamide decomposition proceeds with retention of configuration6i 0... 

The method outlined here works well for amides of primary carbinamines. For amides of secondary carbinamines, lower temperatures must be used, and solvents such as methylene chloride are used in place of the acetic acid (the amide need not be completely soluble in the solvent) the procedure of White and Aufdermarsh6 used for a trimethylacetamide is recommended in such a case. Nitrosoamides of tertiary carbinamines are very unstable, and the salt method of preparation is suggested for these compounds 6... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

N-Substituted amides can be converted to N-nitrosoamides, which are more easily hydrolyzable than the orginal amide. For example, see Rull, M. Serratosa, F. Vilarrasa, J. Tetrahedron Lett., 1977,A5A9. For another method of hydrolyzing N-substituted amides, see Flynn, D.L. Zelle, R.E. Grieco, PA. J. Org. Chem., 1983, 48, 2424. Ladenheim, H. Bender, M.L. J. Am. Chem. Soc., 1960, 82, 1895. 

Scheme 11.11 gives some representative preparative reactions based on these methods. Entry 1 is an example of the classical procedure. Entry 2 uses crown-ether catalysis. These reactions were conducted in the aromatic reactant as the solvent. In the study cited for Entry 2, it was found that substituted aromatic reactants such as toluene, anisole, and benzonitrile tended to give more ortho substitution product than expected on a statistical basis.180 The nature of this directive effect does not seem to have been studied extensively. Entries 3 and 4 involve in situ decomposition of A-nitrosoamides. Entry 5 is a case of in situ nitrosation. 

Lijinsky, W. and D. Schmal. 1978. Carcinogenesis by nitroso derivatives of methylcarbamate insecticides and other nitrosoamides in rats and mice. Pages 495-501 in E.A. Walker, M. Castenegro, L. Griciute, and R.E. Lyle (eds.). Environmental Aspects of N-nitroso Compounds. World Health Qrg., Int. Agency Res. Cancer, IARC Sci. Publ. 19. 

A comparison of structures of V-methyl-V-nitroso-p-nitrobenzamide, N,N -dimethyl-V-nitrosourea, V-methyl-V-nitrosourea, 2-nitroso-2-azabicyclo[2.2.2]octan-3-one to those of V-methyl-V -nitro-V-nitrosoguanidine and V,V -dimethyl-V"-cyano-V-nitrosoguanidine shows that the N—N and C—NNO bond lengths in the nitroguanidines44 are similar to those found in the nitrosoamides, but that the corresponding bonds in... 

Nitrosyl ligands have relatively poor fx-donor capabilities, but are excellent rr-acceptors. There are synthetic routes to nitrosyl complexes using NO gas, [NO][Bp4] or [NOJIPFg], hydroxyamine hydrochloride, HNO3, NaN02, or A -nitrosoamides. 

Dimerization of alkoxyamidyls formed by thermolysis of N-alkoxy-Af-nitrosoamides , A-alkoxy-A-bromo- or A-iodoamides or photolysis of N-alkoxy-Af-chloroamides has been reported, but yields of the hydrazines were lower and esters were secondary products (Scheme 31). 

Two papers describing the intramolecular ene cyclization for the preparation of C6 functionalized pteridines has appeared. Thus 4-amino-5-nitrosopyrimidines such as 249 reacted with a,/3-unsaturated acid chlorides acylating at the 6-amino group group to afford nitrosoamides 250 which on thermolysis in toluene underwent the pericyclic cyclization and subsequent loss of water to afford a mixture of the E- and Z-isomers of the 6-oxopteridine 251 in good yield <2006HCA1140, 2007HCA521>. 

General Preparation of N-Alkyl-N-nitrosoamides with Sodium Nitrite in Acetic... 

The stability of A-nitroso derivatives of aromatic amines varies over a wide range. This variation appears to be related to the substituents on the aromatic nucleus. Nitrosoamides also may decompose photolytically, particularly in an acid medium [39]. 

Another example, using an acetic acid-acetic anhydride solution with sodium nitrite, is the preparation of iV-nitroso-JV-benzyl-p-toluenesulfon-amide [60]. This nitrosoamide (Preparation 9-1) is said to be quite stable at room temperature. 

Alkyl Af-nitroso-A -alkylcarbamates, 441 N-Alkyl-N-nitrosoamides, 435 7V-Alkyl-7V-nitroshydroxylamines, 447 l-Alkyl-2-phenylhydrazines, 327 Allene dipropargyl phosphonate, 31 Allenes, 1-40, see also names of specific allenes, 1,2-Dienes... 

The workup of the final product is similar to that outlined in Procedure 3-1, i.e., extraction of the product with ether followed by a wash with cold water, aqueous 5 % sodium carbonate solution, and water followed by drying with anhydrous sodium sulfate. The solvent then is removed under reduced pressure and, depending on the properties of the final product, purification is accomplished either by distillation under reduced pressure at temperatures below 40°C or by recrystallization from an ether-pentane mixture. In the case of unstable nitrosoamides, these operations have to be carried out at 0°C. 

The products formed in deamination depend on the lifetimes of the different ion-pair species, which, in turn, depend on the structure of the amine and the nature of the solvent. The counter-ion in such reactions can conveniently be varied by using N-nitrosoamides as starting materials. These compounds react to give diazonium ion-pairs in reactions that closely resemble amine deamination, and the lifetime of the ion-pairs can be studied by using lsO-labelled ni-trosoamides (see Scheme 2, XH = solvent or added nucleophile). 

A similar trend has been observed for the closely related, N-nitrosoamide decomposition see Ref. 23. 

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