By the Barton reaction

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

A radical approach to asymmetnc iildol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a tutroalkene, has been reported, as shown in Eq 4 93 The radical precursor is prepared from the corresponding carboxyhc acid by the Barton reaction, which has been used for synthesis of new fi-lactams ... 

Irradiation of octyl nitrite has already been described Kabasakalian et al. have also studied the behavior of its lower homologs.24 It was observed that primary alkyl nitrites with more than four carbon atoms in a chain produced essentially identical yields (37 to 45%) of nitroso dimer formed by the Barton reaction until the minimum straight-chain length of four carbon atoms was reached. Butyl nitrite underwent internal hydrogen abstraction in poor yield. This is the result of a more difficult abstraction of a primary hydrogen as compared to a secondary hydrogen atom available in compounds with longer chains. Reaction paths 2 and 4 predominated to afford 1-butanol and butanal as the major products. 

Scheme 2. Remote functionalization of steroids by the Barton reaction.

A tandem remote functionalization by an excited nitro group, which involves a photochemical nitro-nitrosoxy rearrangement followed by the Barton reaction, is outlined in Scheme 11 [11], Thus, the photolysis of 6/3-nitrocholest-4-ene in methanol by 254 nm light gave 19-hydroxyiminocholest-4-ene 6-/3-ol and its 5-ene 4/3-ol... 

By the Barton reaction a methyl group in the 5-position to an Hydroxyl group can be oxidized to a —CHO group. 

Lead Monoxide. Lead monoxide (litharge), PbO, occurs as a reddish alpha form, which is stable up to 489°C where it transforms to a yellow beta form (massicot). The latter is stable at high temperatures. The solubihty of a-PbO ia water is 0.0504 g/L at 25°C the solubihty of the p-PbO is 0.1065 g/L at 25°C (40). Lead monoxide is amphoteric and dissolves ia both acids and alkahes. In alkahes, it forms the plumbite ion PbO - The monoxide is produced commercially by the reaction of molten lead with air or oxygen ia a furnace. Black or gray oxide is manufactured by the Barton process, by the oxidation of atomized molten lead ia air, as well as by the ball mill process, ia which metallic lead balls of high purity are tumbled ia the mill to form partially oxidized lead particles. 

Ono and Lash have been the two pioneers in applying the BZ reaction to the synthesis of pyrroles and, particularly, with applications to the synthesis of novel fused and other porphyrins. Although the concept was recognized by Barton and Zard, Ono and Lash independently discovered the conversion of 2-pyrrolecarbo ylates, prepared by the BZ reaction, into porphyrins by what is now a standard protocol (1. LiAlfL 2. 3. 

Nitrous acid esters 1 can be converted to 3-nitroso alcohols 2 by irradiation with ultraviolet light. This conversion is called the Barton reaction. ... 

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

The Barton reaction is usually carried out by irradiation of a nitrite ester 1 dissolved in a hydroxyl-free solvent under nitrogen atmosphere. Possible side-reactions can be decomposition reactions and intermolecular reactions sometimes the disproportionation may even predominate ... 

The Hofmann-Loeffler-Freytag reaction has been described with A-chloro-as well as A-bromoamines—the former however usually give better yields. A-chlorinated primary amines react well in the presence of Fe-(II) ions. Just like the Barton reaction, the Hofmann-Loeffler-Freytag reaction has been applied mainly in steroid chemistry. An interesting example from alkaloid chemistry is the synthesis of nicotine 12 by Loeffler ... 

Heterocyclic aromatic nitro compounds are more reactive toward nucleophiles than carbo-cyclic aromatic nitro compounds Various heterocyclic aromatic nitro compounds are thus converted into the corresponding pyrroles by the Barton-Zard reaction fEq 10 37 ... 

Another related reaction is the Barton reaction, by which a methyl group in the 0 position to an OH group can be oxidized to a CHO group. The alcohol is first converted to the nitrite ester. Photolysis of the nitrite results in conversion of the nitrite group to the OH group and nitrosation of the methyl group. Hydrolysis of the oxime tautomer gives the aldehyde, for example,... 

Photolysis of 2-propylnitrite, in which intramolecular hydrogen abstraction cannot occur via a six-membered transition state, results in a 30% yield of 2-propanone. As we shall see, this intramolecular hydrogen abstraction has been extensively applied to steroid syntheses by D. H. R. Barton and hence is commonly referred to as the Barton reaction. 

Pyrroles prepared by the Barton-Zard reaction are very important as precursors of porphyrins and also of conducting polymers. The ester group at the 2-position is readily removed on heating with KOH in ethylene glycol at 170 °C to give a-free pyrroles, which are useful for preparing porphyrins (Eq. 10.42)47 or polypyrroles (Eq. 10.43).38a,4S... 

The formation of the oxime (2) probably results from the presence of adventitious traces of hydroxylic material which catalyze the isomerization of the nitroso monomer, the primary product of the Barton reaction, to an oxime. More direct evidence for the formation of nitroso compounds in the photochemical rearrangement of nitrites is provided by the isolation of nitroso dimers. ... 

In a similar manner, 11/3-nitrites, on photolysis, attack Ci to furnish the corresponding oximes which, upon nitrous acid treatment, gave 18-oxygenated steroids. The most spectacular application of the Barton reaction has been a three-step synthesis of aldosterone.12 Irradiation of corticosterone-11-nitrite (27, R = NO), followed by nitrous acid treatment, gave aldosterone (29) in 15% overall yield. Comparable conversions of 11/3-hydroxyprogesterone to 21-desoxyaldosterone12 and A1-corticosterone to A aldosterone14 have also been achieved. 

The mechanism of the Barton reaction may be represented by the three discrete steps shown in sequel A — D (Scheme II). First, the photochemical cleavage of the O-N bond in A to furnish the alkoxy... 

The Barton reaction is strongly inhibited by the addition of t-butyl nitrite, unpublished observations at the Institute. 

The oxygen atom of the activated alkoxy radical and the hydrogen to be abstracted and subsequently replaced by X, form two adjacent corners of the six-membered transition state. The major application of the Barton reaction have been in the synthesis of steroids particularly with compounds involving functionalization of Clg and C,9 which is difficult to achieve in other ways. 

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