Amides photochemistry

The effect of substituents on the temperature dependence of a-carbonyl-carbene reactivity has been examined using carbenes generated by low-temperature photolysis of methyl diazophenylacetate. A correction to the literature on the photoreaction of isopropylidene diazomalonate (98) with 1,3,3-trimethyl-cyclohexane (99) has been reported. The photoproduct, originally thought to be a cyclopropane derivative, has now been shown to be the cyclobutanone (100), the formation of which presumably involves a photo-Wolff rearrangement as illustrated in Scheme 11. Substituent effects observed in the product distribution of diazo-amide photochemistry have been ascribed to conformational factors the jS-lactam, oxindole, and Wolff rearrangement products appear to arise directly from the excited singlet state of the sym-Z form of the diazo-amide itself. 

The photochemistry of linearly conjugated 2,4-cyclohexadiene-l-ones (e.g. 4) has been studied extensively7. These linearly conjugated systems generally photorearrange to a (Z)-dienylketene 5 (equation 1) this process is usually reversible, so that in the absence of a nucleophile little change is observed. In the presence of amines or alcohols, however, amides and esters are typically isolated. In the presence of weaker nucleophiles a slow formation of phenol derived products is usually observed. 

The intramolecular photochemistry of the vinylogous amide 173 in terf-butyl alcohol yielded a retro-Mannich type reaction product 174 (equation 114)170. 

Compared to amides, the photochemistry of thioamides was less studied. The 2-substituted aryl thioamide 175 undergoes photocyclization to quinoline derivatives (equation 115)171. 

Finally the effects of conformation, hydrogen bonding and Lewis acids on the intramolecular electron transfer, spectroscopy and photochemistry of amides were recently studied174-176 (equations 119-121). 

The amide functionality plays an important role in the physical and chemical properties of proteins and peptides, especially in their ability to be involved in the photoinduced electron transfer process. Polyamides and proteins are known to take part in the biological electron transport mechanism for oxidation-reduction and photosynthesis processes. Therefore studies of the photochemistry of proteins or peptides are very important. Irradiation (at 254 nm) of the simplest dipeptide, glycylglycine, in aqueous solution affords carbon dioxide, ammonia and acetamide in relatively high yields and quantum yield (0.44)202 (equation 147). The reaction mechanism is thought to involve an electron transfer process. The isolation of intermediates such as IV-hydroxymethylacetamide and 7V-glycylglycyl-methyl acetamide confirmed the electron-transfer initiated free radical processes203 (equation 148). 

Chapter 2, by Miranda and Galinco, provides a critical survey of the photo-Fries reaction undergone by numerous aromatic esters, amides, and so forth. This chapter is a valuable companion to Chapter 5 by Fleming and Pincock, in Volume 3. Miranda and Galinco s chapter is the sixth chapter devoted to the photochemistry of aromatic compounds in this series. 

There are a number of reports in the literature on the photochemistry of amides, including the photodegradation of serum albumin,224 and of polypeptides.1 Photodegradation involves reactions of acyl and imine free radicals generated by photolytic scission of the amide group.23 33 The photooxidation of N-pentylhexanamide led to the formation of n-valeraldehyde and valeric acid from the amine part of the molecule... 

The amidation of unsaturated acids or esters (not necessarily a,(3 unsaturated ones) leads to derivatives of the corresponding dicarboxylic acids and may serve as a method for the synthesis of dicarboxylic acids from unsaturated monocarboxylic acids (10,13, 14). This reaction of formamide with oc,(3-unsaturated acid derivatives besides being of synthetic value has some interesting aspects as far as free radical chemistry and photochemistry are concerned. We shall start this section in discussing the last point, i.e. the photochemical aspects of the reaction. This point is of primary interest to the synthetic organic chemist, who must be aware of it, otherwise he may fail in his synthetic work purely because of photochemical reasons. 

Coumarin photochemistry has been recently employed to demonstrate that a frozen axial chirality can be used to induce the absolute configuration of stereogenic centers. Coumarin 103 was obtained as a single atropisomer by spontaneous crystallization (Scheme 6.37). Upon warming powdered crystals of 103 in MeOH to —20 °C, sensitized [2 + 2]-photocydoaddition to ethyl vinyl ether gave the almost enantiomerically pure products 104. The approach to the coumarin double bond occurred preferentially from the less-shielded face to which the amide carbonyl group... 

The extension of this intramolecular photocycloaddition-retro-Mannich-Mannich sequence to -substituted secondary vinylogous amides, the photochemistry of which had been originally reported by Schell and Cook (Scheme 18), was also examined... 

The photochemistry of vinylogous amides is not limited to [2 + 2] photoadditions. This section will describe some of the migration and fragmentation reactions observed on irradiation of vinylogous amides. Schell and coworkers have reported that irradiation of 125 leads to the formation of 126, the formal product of an aza-Claisen reaction, in 57% yield (equation 16)40. 

The photochemistry of 2-acyl-vinylogous amides has also been investigated by Tamura and coworkers, who reported that irradiation of 142 (R1 = CH2R R2 = H R1 = R2 = CH2R) through a quartz filter in methylene chloride led to the formation of the dealkylated product 143, albeit in modest yield (equation 19), both in the case of... 

While some of the mechanistic details for the examples described in this chapter have not yet been fully elucidated, it is clear from the scope of the examples discussed herein that the photochemistry of enaminones and enamidones is a fascinating research area. The novel sequence for the annelation of imidazole rings onto a preexisting structure, the synthesis of perhydroindoles via vinylogous amide [2 + 2] photocycloaddition chemistry and the enamide cyclization reactions all underscore the enormous utility of these chromophores in the development of new reactions and novel synthetic methods. 

The free radical (139), formed by the irradiation of ptentachlorocyclopen-tadiene, reacts with ethers, acids, amides, esters, and hydrocarbons to yield 5-substituted derivatives of the cyclopentadiene (140)7 A study of the photochemistry of C-labelled pentamethylcyclopentadienes has been rep orted7 ... 

Laser flash photolysis has also been used to study the photophysics and photochemistry of metallocene-containing cryptands and their complexes with rare earth eations [69]. The metallocene moiety was shown to act as an efficient centre for the radiationless deactivation of the lanthanide excited state. Detailed time-resolved studies permitted the characterisation of the coordination chemistry about Dy " within the cryptate and showed, once again, that the functions within the host cryptand primarily responsible for coordination of the guest cation were the amide carbonyl groups. 

Further studies on the photoisomerization of ci5-cyclohexene and cycloocta-1,3-diene have been reported. Again the work has focused on enantiodiffer-entiation. In this case a series of optically active chiral sensitisers (3) have been used under conditions where solvent and temperature have been varied. Some of the o-disubstituted and tetra substituted amide sensitisers afford mixtures with enantioisomeric excesses of 14%. The influence of pressure and temperature on the asymmetric photochemistry of cyclooctene has been reported. A variety of chiral sensitisers were used. Some of these are shown in (4). Other work has shown that aromatic phosphates, phosphinates and phosphines (e.g. 5-8) can also sensitise the isomerism of cyclooctene. Moderate stationary-state ratios were obtained. 

The photochemistry o oxaziridines has been independently investigated. Regiospecific photorearrangements of spiro-oxazirid-ines derived from 2-methylindan-1-one, 2-methyltetral-1-one and 1-methyltetral-2-one have been reported.The oxaziridines (65), for example, are converted on irradiation in ethanol into the lactams (66). A one-photon pathway resulting in ring cleavage and amide formation has also been observed in the gas-phase irradiation... 

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