Reactive Intermediate Chemistry

466 ATOMIC CARBON

into an organic molecule of biological interest that is injected into the subject and imaged by PET. These sophisticated studies are often made more challenging by the fact that 11C has a 20.4-min half-life and syntheses of relevant biomolecules must be rapid. Although a detailed discussion of the use of 11C in nuclear medicine is beyond the scope of this chapter, a particularly clever example reported by Lifton and Welch15 will be mentioned. These workers generate 11CO2, which they expose to a green leaf in the presence of light. Photosynthesis converts the 11CO2 into 11C labeled glucose, which is separated, injected into the patient, and imaged by PET to monitor brain metabolism.

2.2. Graphite Vaporization Methods

2.2.1. The Carbon Arc. The use of the carbon arc to investigate the reactions of atomic carbon was first reported by Skell and Harris in 196516 and was reviewed by Skell et al.4 in 1973. This technique was employed extensively by the Skell group and has more recently become an important method of investigating C atom reactions in our research group. Figure 10.1 shows a diagram of a typical carbon arc apparatus for generating and studying the reactions of C atoms. The reaction chamber is evacuated to 1 m Torr, and a carbon arc is struck between two graphite rods attached to water-cooled brass electrodes. Atomic carbon is vaporized by the arc and deposited on the cooled walls of the reaction vessel along with substrate introduced through an inlet tube. Although various low-temperature baths have been used to cool the reactor walls, most reactions have been run at liquid nitrogen temperatures (77 K). At the conclusion of the reaction, the reactor is warmed and the products are removed and analyzed by the traditional instrumental methods of organic chemistry [gas chromatography (GC), GC–mass spectrometry (GC/MS), nuclear magnetic resonance (NMR), infrared (IR), etc.). An advantage of this method is the fact that it is relatively easy to produce carbon vapor enriched in 14C17 and 13C.18 The use of 13C atoms allows an NMR determination of the position of the attacking carbon in products facilitating mechanistic evaluations.18

While the carbon arc method yields products in amounts that are easily characterized, there is a number of caveats of which one must be aware. Since the carbon arc operates at extremely high temperatures (>2000 C) and emits copious amounts of light, there is the very real possibility of pyrolysis and/or photolysis of both substrate and products. These problems may be minimized by carrying out control experiments in which pyrolysis and photolysis products are identified and excluded. Maximum yields in carbon arc reactions are obtained when carbon and substrate are cocondensed. However, this technique can result in pyrolysis of substrate, which can be avoided by alternately depositing substrate and carbon on the cold reactor walls. Often both methods are employed in order to identify pyrolysis products. Since the carbon arc results in removal of macroscopic pieces of graphite from the rods, it is impossible to measure product yields based on actual carbon evaporated.

Figure 10.1. A typical carbon arc reactor.

Another complication in carbon arc studies is the fact that molecular carbon species, C2 and C3, are also produced when the arc is struck under high vacuum.19 This ‘‘problem’’ can be a positive aspect of these reactions as it allows studies of the reactions of the molecular carbon species. When the arc is struck in the presence of an inert gas, the situation is more complex with fullerenes resulting.20 We have not observed fullerene formation from a carbon arc under high vacuum.21

2.2.2. Resistive Heating of Graphite. Another method of generating atomic carbon is the simple resistive heating of graphite or a carbon fiber.22,23 These reac-

tions have also been carried out by cocondensing carbon with substrate. However, this method leads only to ground state C(3P) atoms,23,24 which are relatively

unreactive toward organic compounds under these conditions. In contrast, the carbon arc generates both ground-state triplet and excited singlet C atoms that react with organics in many interesting ways.

2.3.3. Diazo Compounds as Carbon Atom Precursors. An attractive strategy for the generation of a C atom employs a diazo compound as a chemical precursor. Diazo compounds are well known to generate carbenes with the loss of the stable N2 molecule. The trick is to design a diazo compound in which cleavage of the remaining two bonds in the initial carbene is energetically feasible. Two such diazo compounds have been designed and used in this way. The first is the quadricyclic diazo compound 4, which has been proposed to decompose to carbene 5, and thence to a C atom with the loss of benzene (Eq. 5).33 Since 4 is rather tedious to synthesize and its thermolysis also produces benzene, which is reactive toward C, this interesting compound has received only limited attention as a C atom precursor.

A more extensively investigated precursor to chemically generated C atoms is diazotetrazole (6), which is easily prepared from readily available 5-aminotetrazole (7).34 In this method, 7 is converted into the corresponding diazonium chloride 8, which is coated on the walls of a flask and pyrolysed in the presence of a gaseous substrate (Eq. 6). This technique has the drawback that 8 is extremely explosive and only small quantities can be prepared at a time.34c However, the synthesis of 7 with a labeled carbon is quite simple, allowing convenient evaluation of the fate of the reacting carbon.34b

A potential problem in the use of diazo compounds as C atom precursors is the fact that intermediates in these reactions may act as C donors with the free atoms not involved. Indeed, the timing of the reactions in Eq. 6 is unknown and some of these intermediates may be bypassed in the thermolysis of 8. However, a comparison of the reactions of carbon from 8 with those of nucleogenic and arc generated carbon reveals quite similar products from many different substrates and provides circumstantial evidence for free C atoms in the decomposition of 8.

3.2. Reactions of Carbon Atoms with Inorganic Substrates

Reaction of C(1D) with H2 gives CH þ H38 and C(3P) is thought to produce

3CH2.29,39 Triplet carbon reacts rapidly with oxygen to give carbon monoxide and O(3P).10,40 This extremely facile reaction of C(3P) can be used to deduce the

spin state of a reacting carbon.39a For example, carbon may be allowed to react with a substrate, the products identified, and the reaction repeated in the presence of oxygen. If the product yields are not reduced in the presence of oxygen, these products are taken to result from the reaction of singlet C atoms. These experiments have led to the conclusion that the majority of products from the reactions of nucleogenic, arc generated, and chemically generated carbon are from the singlet state. The formation of CO in these systems indicates that C(3P) is formed but is rather

HF,47 Cl2,48 and F2,49 is reported to give the corresponding halo and dihalocarbenes.

3.2.1. Formation of Amino Acid Precursors in the Reaction of Carbon Atoms with Ammonia. When arc generated carbon is cocondensed with ammonia at 77 K, the volatile products are hydrogen cyanide and methylamine. Hydrolysis of the nonvolatile products generates a number of simple amino acids (Eq. 9).50 The mechanism of this reaction involves initial C H insertion to give aminocarbene (9), which either rearranges to methylenimine (10) or loses H2 to give HNC.51 Rearrangement of HNC produces HCN. Addition of HCN to 10 gives aminoacetonitrile (11), which may be hydrolyzed to glycine (12) (Eq. 10). The methylamine results from the addition of methylene (formed by H abstraction) to ammonia or H abstraction by 9. A series of reactions with methylamine analogous to those in Eq. 10 leads to alanine (13) and N-methylglycine (14). The aspartic acid (15) is most likely formed by a second addition of C to 10 to give a ketenimine that subsequently adds ammonia and two molecules of HCN. When water is cocondensed with C þ NH3, serine is formed in addition to the products in Eq. 9.

ð14Þ

The fact that simple biochemicals are generated in these C atom reactions provides a potential pathway to these molecules under extraterrestrial conditions. It is easy to imagine interstellar C atoms condensing on a cold surface with known interstellar molecules such as NH3, H2O, HCN, and CH2 O.

3.3. Reaction of Carbon Atoms with Simple C H Bonds

Like many singlet carbenes, nucleogenic, arc generated and chemically generated C atoms react with aliphatic C H bonds by insertion. In the simplest case, reaction of chemically generated C atoms with methane yields ethylene and acetylene.56 When a mixture of CH4 and CD4 is used, product analysis indicates that the acetylene results from H abstraction followed by dimerization of the CH, while the ethylene results from C H insertion followed by H migration in the carbene (Eq. 15). It seems probable that CH is formed in all reactions of carbon with hydrocarbons as acetylene is invariably produced in these reactions.

HC CH

Unactivated C H bonds appear to react rather indiscriminately with C atoms to give the corresponding carbene. For example, reaction of chemically generated car-

bon with propane gives products that are consistent with initial insertion into both the 1 and 2 C H bonds to give the corresponding carbenes (Eq. 16).34c The pro-

ducts in Eq. 16, although in slightly different ratios, are also formed in the reaction of arc generated57 and nucleogenic carbon58 with propane.

3.4. Reaction of Carbon Atoms with Alkenes

In analogy with carbenes, atomic carbon reacts with alkenes by double-bond addition (DBA) to give cyclopropylidenes such as 19, which undergo the known ring

In order to confirm these mechanistic conclusions, carbenes 23 and 24 have been generated by the C atom deoxygenation of (E)- and (Z)-3-phenylpropenal (25 and 26). Deoxygenation of 25 gives 21 and 22 in a 8.5:1 ratio, while deoxygenation of 26 yields 21 and 22 in a 0.13:1 ratio (Eqs. 19 and 20). These results indicate that carbenes 23 and 24 undergo intramolecular reaction faster than they interconvert.

ð20Þ

In a related reaction, arc generated 13C atoms react with 22 to generate naphthalene labeled in the 2-position. Double labeling experiments and calculations implicate an initial C H insertion to produce 2-indenylcarbene 27 followed by ring expansion and H migration (Eq. 21). Independent production of 27 by C atom deoxygenation of the corresponding aldehyde also generates naphthalene (Eq. 21).63

ð21Þ

3.4.1. Reaction of Carbon Atoms with Cycloalkenes to Give Cyclic Cumulenes. Since carbon is known to react with acyclic double bonds to generate cumulenes via a cyclopropylidene, a straightforward extension takes advantage of the high energy of atomic carbon as a potential route to cyclic cumulenes. Thus, reaction of arc generated carbon with cyclopentene in an attempt to prepare 1,2-cyclohexadiene (28) by DBA via an intermediate cyclopropylidene results in