Decarboxylative nitrosation

Chlorofluoronitronitrosomethane (380) was obtained by the decarboxylative nitrosation of chlorofluoronitroacetic acid (379)419. 

Girard, P., Guillot, N., Motherwell, W. B., Hay-Motherwell, R. S., Potier, P. The reaction of thionitrites with Barton esters a convenient free radical chain reaction for decarboxylative nitrosation. Tetrahedron 1999, 55, 3573-3584. 

Scheme 28. Product evolution from decarboxylative nitrosation...

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Nilrosated fluoro compounds are frequently prepared by electrophilic nitrosation on an electron-nch center of oxygen, nitrogen, or carbon The preparation of fluorochloronitronitrosomethane from the decarboxylation of fluorochloronitro-acetic acid in nitric acid is unique [f ] (equation 1)... 

In a study of the nitrosation of camphor-3-glyoxylic acid (89), Chorley and Lapworth isolated a compound whose structure (90) has recently been clarified by Hatfield and Huntsman. Decarboxylation and ring expansion occur and the reaction is rationalized in the sequence 89 90. The buttressing effect of a methyl group on... 

How proline is converted to NPYR has not yet been fully elucidated and could conceivably occur by either of two pathways (29, ). One pathway involves the initial N-nitrosation of proline, followed by decarboxylation, while in the other, proline is first decarboxylated to pyrrolidine followed by N-nitrosation to NPYR. Since the conversion of N-nitrosoproline (NPRO) to NPYR occurs at a much lower temperature than the transformation of proline to pyrrolidine, the pathway involving intermediacy of NPRO is thus the more likely route ( ). It has been reported that preformed NPRO in raw bacon is not the primary precursor of NPYR in cooked bacon (29,33-5), as shown by the fact that ascorbyl paImitate, when added to bacon, inhibits the formation of NPYR (33). However, this by no means rules out the intermediacy of NPRO which could be formed at the higher temperatures attained during the frying process (29,36). 

Since nicotine is the major precursor to NNN in tobacco and tobacco smoke, the reaction of nicotine with sodium nitrite was studied to provide information on formation of other tobacco specific nitrosamines, especially NNK and NNA, which could arise by oxidative cleavage of the l -2 bonds or l -5 bond of nicotine followed by nitrosation (26). The reaction was investigated under a variety of conditions as summarized in Table I. All three nitrosamines were formed when the reaction was done under relatively mild conditions (17 hrs, 20 ). The yields are typical of the formation of nitrosamines from tertiary amines (27). At 90 , with a five fold excess of nitrite, only NNN and NNK were detected. Under these conditions, both NNK and NNA gave secondary products. NNK was nitrosated a to the carbonyl to yield 4-(N-methyl-N-nitrosamino)-2-oximino-l-(3-pyridyl)-1-butanone while NNA underwent cyclization followed by oxidation, decarboxylation and dehydration to give l-methyl-5-(3-pyridyl)pyrazole, as shown in Figure 4. Extensive fragmentation and oxidation of the pyrrolidine ring was also observed under these conditions. The products of the reaction of nicotine and nitrite at 90 are summarized in Table II. 

The anion formed from the acetyl methyl group under reaction conditions then attacks one of the carbethoxy groups to form a cylohexanone to give (74-4) as the isolated product. The free acid obtained on hydrolysis of the ester decarboxylates to give the (3-diketone (74-5). In a classic apphcation of the Knorr pyrrole synthesis, the diketone is then allowed to react with 2-aminopentan-3-one. Since the latter is unstable, it is generated in situ by reduction of the nitrosation product from diethyl ketone. There is thus obtained piquindone (74-6) [76], a compound that displays antipsychotic activity. 

Isonitrosopropiophenone has been prepared from esters of a-benzoylpropionic acid by a process involving saponification, nitrosation, and decarboxylation from phenyhnethylglyoxal by the action of hydroxylamine from propiophenone by treatment with amyl nitrite, methyl nitrite, or butyl nitrite. ... 

The structure of the western corn rootworm sex pheromone is 8-methyl-2-decanol propanoate (] 6) and four stereoisomers are possible (Figure 7). In our synthesis (3), we coupled a chiral 5-carbon unit to a 6-carbon fragment that had the requisite substitution to allow resolution at the oxygenated carbon. As mentioned earlier, (S)-2-methylbutyric acid was available to us from the alcohol. D-Isoleucine served as a source for the (R)-acid. Nitrosation, followed by decarboxylative oxidation of the intermediate hydroxyacid led to the (R)-2-methylbutyric acid in 96% ee. The process of fractional crystallization was... 

Some further monosubstituted furoxans which have been reported are either of very doubtful authenticity or have been discredited. The phenacyl derivatives of Harries and Tietz,462 formed by the nitrosation of /J-aryl-oc,/ -unsaturated oximes, have been shown to be pyrazolone di-JV-oxides 463 The degradation of Holleman s peroxide (29) by hydroxylamine and alkali was reported to form structure 218, or its 3-substituted isomer, by Boyer and Chang.29 It does, however, seem unlikely that a monosubstituted furoxan could withstand such reaction conditions. Decarboxylation of furoxandi-carboxylic acid has been suggested to provide the 4-monocarboxylic acid,464 but Ponzio and De Paolini465 have assigned a nitrile oxide structure to the product. 

Primary and secondary nitroso compounds usually stabilize themselves, even under the conditions of their preparation, by passing irreversibly into their isomers, the oximes. In tertiary aliphatic nitroso compounds this transformation is accompanied by fission of the neighboring carbon-carbon bond by hydrolysis or decarboxylation. Aromatic nitroso compounds are more stable, and when oxime formation does occur this is usually reversible within the framework of a true tautomeric equilibrium for instance, the tautomeric pair -nitrosophenol/p-benzoquinone monooxime is obtained both by nitrosation of phenol and by oximation of />-benzoquinone. 

There are a number of variations of this pattern which have been developed. The a-aminocarbonyl compounds are usually generated in situ by nitrosation/reduction <93T2185>. For some systems it is preferrable to carry out the reduction by catalytic hydrogenation <85JOC5598>. Aminomalonate esters can be used when the desired product is a pyrrole-2-carboxylate. Decarboxylation occurs during the course of the reaction so that the aminomalonate is a glycine equivalent (Equation (47)) <87JOC3986>. 

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