Reactions fragmentation

The fragmentation can be concerted or stepwise. The concerted mechanism is restricted to molecular geometry that is appropriate for continuous overlap of the participating orbitals. 

An example is the solvolysis of 4-chloropiperidine, which is more rapid than the solvolysis reactions 

Diols or hydroxy ethers in which the two oxygen substituents are in a 1,3-relationship are particularly useful substrates for fragmentation. If a diol or hydroxy ether is converted to a monotosylate, the remaining hydroxyl group can serve to promote fragmentation. 

A similar reaction pattern can be seen in a fragmentation used to construct the ring structure found in the taxane group of diterpenes. 

Similarly, a carbonyl group at the fifth carbon from a leaving group, reacting as the enolate, promotes fragmentation with formation of an enone.49 

Fragmentation reactions are particularly common in small rings. Relief of strain and the gain in stability in forming certain common fragments (such as N2, CO2), as felt in the 

Nitrogen, CO2, SO2, RCN, RNCO and RNCS are particularly common fragments containing two of an original four ring atoms. 

Most of the chemical reactions occur in the condensed phase or in the gas phase under conditions such that the number of intermolecular collisions during the reaction time is enormous. Internal energy is quickly distributed by these collisions over all the molecules according to the Maxwell-Boltzmann distribution curve. 

Grob has reviewed the mechanisms of fragmentation of y-amino derivatives. Examples of unimolecular, bimolecular, and ElcB-type fragmentations are discussed (cf. Section 8). 

The name fragmentation applies to reactions in which a carbon-carbon bond is broken when an electron deficiency develops. A structural feature that permits fragmentation to occur readily is the presence of a carbon beta to the developing electron deficiency that can readily accept carbonium ion character. This type of reaction occurs particularly readily when the 7-atom is a heteroatom, such as 

The Beckmann rearrangement reaction provides a number of examples of fragmentation. The products that result from fragmentation are a carbonium ion and a nitrile. Fragmentation is very likely to occur if X is a nitrogen, oxygen, or 

Organoboranes have been shown to undergo fragmentation if a good leaving group is present on the 5-carbon.The reactive intermediate is the tetrahedral intermediate formed by addition of hydroxide ion at boron. 

McManus (ed.), Organic Reactive Intermediates, Academic Press, New York (1973). 

CHAPTER 8 REACTIONS INVOLVING ELECTRON-DEFICIENT INTERMEDIATES 

Reactions Involving Carbocations, Carbenes, and Radicals as Reactive Intermediates 

P-Hydroxyketones are also subject to fragmentation. Lewis acids promote fragmentation of mixed aldol products derived from aromatic aldehydes.100 

The fragmentation can be concerted or stepwise. The concerted mechanism is restricted to molecular geometry that is appropriate for continuous overlap of the participating orbitals. An example is the solvolysis of 4-chloropiperidine, which is more rapid than the solvolysis of chlorocyclohexane and occurs with ring opening by fragmentation of the C-2—C-3 bond.  

CHAPTER 10 REACTIONS INVOLVING CARBOCATIONS, CARBENES, AND RADICALS AS REACTIVE INTERMEDIATES 

Now that we have covered the major rearrangement reactions, we will now look at a few fragmentation reactions. 

Fragmentation of a molecule may occur in many different ways. The following examples will give you a feel for some of the different mechanisms that can be invoked. 

The fragmentation reaction that is most often first encountered is the iodoform reaction. This is because it forms the basis of a very easy qualitative test for the presence of a methyl ketone, or alternatively the CH3CH(OH)- grouping. If a methyl ketone is treated with iodine and sodium 

Another example of this type of reaction is the decarboxylation of aliphatic acids. For the decarboxylation to proceed easily there must be an electron withdrawing group capable of stabilising the negative charge. An example would be an a-ketoacid, e.g. RCOCOOH. Suggest a mechanism for this reaction. 

The mechanism is essentially either an SE1 or an SE2 process. There are many variations on this theme. For example, the Darzens condensation produces an a,(3-epoxy carboxylic acid, which when heated often undergoes decarboxylation. Suggest a mechanism for this reaction. 

In earlier sections, we have already brought forward several examples of radical fragmentation reactions, although the terminology was not explicitly used. The facile decarboxylation of acyloxy radicals was mentioned earlier. 

For the acetoxy radical, the Ea for decarboxylation is about 6.5 kcal/mol and the rate is about 10 s at 60°C and 10 s at Thus, only very rapid reactions 

Acyl radicals can fragment with loss of carbon monoxide. Decarbonylation is slower than decarboxylation, but the rate also depends on the stability of the radical that is formed. For example, when reaction of isobutyraldehyde with carbon tetrachloride is initiated by t-butyl peroxide, both isopropyl chloride and isobutyryl chloride are formed. Decarbonylation is competitive with the chlorine atom abstraction. 

Another common fragmentation reaction is the cleavage of an alkoxy radical to an alkyl radical and a carbonyl compound.  

This type of fragmentation is involved in the chain decomposition of alkyl hypochlorites.  

It has already been discussed under section 2.1. (a) that construction reactions essentially establish carbon-carbon skeletons (bonds) in a tai et-drug-molecules those reactions that specifically cleave carbon-carbon skeletons (bonds) are usually termed as fragmentation reactions . In other words, the former enjoys its existence and importance to build up desired C—C skeletons and, therefore, are absolutely necessary in a synthesis however, the latter causes degradation or split-up of C—C skeletons and they also possess certain vital synthetic utility. There are, in fact, two important reactions that are particularly useful in affording the fragmentation reactions, such as  

1 Ozonolysis. Ozonolysis (cleavage by ozone Og ) is accomplished in two stages, namely first, addition of ozone to the double bond to form an ozonide and secondly, subsequent hydrolysis of the ozonide to produce the cleaved products. 

Example. (1) Ozonolysis of Alkene to yield Aldehydes and Ketones  

Cyclopentene (A) upon ozonolysis undergoes cleavage to give rise to an open-chain compound having carbonyl moieties at C-1 and C-5 positions whereas, cyclohexene (B) 3delds a cleaved product that bears the carbonyl functions at C-1 and C-6 respectively. 

2 Decarboxylation. Decarboxylation, i.e., elimination of the —COOH moiety as CO2, is of restricted and limited utility for aromatic acids, and extremely important for certain (l-keto acids and 3-diacids (or substituted aliphatic acids malonic acids). 

Photodecarboxylation is the major reaction path encountered when the amino-esters (165) are irradiated in non-polar solvents.117 A full account of the photochemical transformations of the naphthylmethyl phenylacetates (166) and (167) 

Kimoto, K. Tanabe, S. Saito, Y. Umeda, and Y. Takimoto, Chem. Letters, 1974, 859. 

Photodecarboxylation of the adducts (169) in benzene solution yields the unstable quinomethides (170a—c) which are sensitive to air exposure and further irradiation.121 Thus the phenyl adduct (169 R = Ph) gave the cyclobutane (171 28%) as well as the dihydronaphthalene (172 23%), and the cyclopropane (173 3.5%) which could arise by an oxa-di-7r-methane process. 

A full report on the synthesis of a-dithiones by the photochemical decarbonylation of vinylenecarbonates has been published.124 

The Norrish Type I fragmentation of the cyclic ketone (178) has been used in a synthesis of grandisol (179), a major component of the male boll weevil pheromone.125 The cleavage reaction gave the aldehyde (180) which was subsequently decarbonylated to give the desired product. 

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On this basis Hendrickson classified organic reactions. A distinction is made between refiinctionalization reactions and skeletal alteration reactions. Refiinctiona-lizations in almost all cases have no more than four carbon atoms in the reaction center. Construction or fragmentation reactions have no more than three carbon atoms in each joining or cleaving part of the molecule. Thus, these parts are treated... 

The steps (reactions) by which normal ions fragment are important pieces of information that are lacking in a normal mass spectrum. These fragmentation reactions can be deduced by observations on metastable ions to obtain important data on molecular structure, the complexities of mixtures, and the presence of trace impurities. 

Linked scanning techniques by which fragmentation reactions can be examined are particularly easy to apply with QqQ instmments. The ease with which RF and DC voltages can be changed rapidly means that the scanning can be done very quickly. Three common and popular types of linked scan are briefly described here and serve to illustrate its principles. 

Finally, accurate mass measurement can be used to help unravel fragmentation mechanisms. A very simple example is given in Figure 38.2. If it is supposed that accurate mass measurements were made on the two ions at 203.94381 and 77.03915, then their difference in mass (126.90466) corresponds exactly to the atomic mass of iodine, showing that this atom must have been eliminated in the fragmentation reaction. 

Benzo[Z)]thiophene reacts with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate in a cyclo-addition-fragmentation reaction to yield (143), whereas benzo[A]furan and N- methylindole yield products (144) arising from ring opening and recyclization (76AP679). 

Aziridine hydrazides, e.g. (310), undergo an interesting fragmentation reaction which results in ring opening and diimide formation (68JA3592). 

SECTION 12.7. REARRANGEMENT AND FRAGMENTATION REACTIONS OF FREE RADICALS... 

Rearrangement and Fragmentation Reactions of Free Radicals 12.7.1. Rearrangement Reactions... 

The most important fragmentation reactions of sulfur diimides occur with polynuclear metal carbonyls, e.g., M3(CO)i2 (M = Fe, in... 

AS n values for fragmentation reactions like the one shown above are typically of the order of 40 to 60 eu (1 eu or entropy unit = 1 cal/mol-K). Use an average value for AS and your calculated AH n to estimate AG at 298 K (use equation 1). Do these new data affect any of your conclusions about which alcohols are likely to be stable and which are likely to be nonexistent ... 

A stereoelectronic requirement in radical addition to carbon-carbon double bonds first became apparent from studies on radical cyelization and the reverse (Fragmentation) reactions.54 56 It provides a rationalization for the preferential formation of the less thermodynamically stable exo-product (i.e. head addition) from the cyelization of to-alkcny] radicals (16 - Scheme 1.5). s 57 G4... 

The reactivity of the monomer and the reaction conditions determine the relative importance of P-scission. Fragmentation reactions are generally favored by low monomer concentrations, high temperatures and low pressures. Their significance is greater at high conversion. They may also be influenced by the nature of the reaction medium. 

B. 5-Hexynal. To a solution of 5.60 g. (0.050 mole) of 2,3-epoxycyclohexanone in 120 ml. of benzene in a 500-ml. round-bottomed flask is added 10.82 g. (0.051 mole) of trans-1 -amino-2,3 diphenylaziri-dine.2 Initially, after brief swirling at room temperature, the reaction mixture is a colorless, homogeneous solution however it rapidly turns yellow and cloudy due to separation of water. After 2 hours the benzene and water are removed as an azeotrope under reduced pressure on a rotary evaporator with the bath maintained at approximately 30°. The resulting crude mixture of diastereomeric hydrazones weighs 15.4 g. (Note 7) and is subjected directly to the fragmentation reaction (Note 8). 

Figure 7.44 Thermal bond rupture (a) fragmentation reaction, (b) oxidation degradation.

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

Fragmentation reactions sometimes accompany Clemmenson reduction. See Bailey, K.E. Davis, B.R. Aust. J. Chem., 1995, 48, 1827. Also see Rosnati, V. Tetrahedron Lett., 1992, 33, 4791. 

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