Beta-carbon

What happens when isomerization is performed is that the double bond of the allylbenzene safrole migrates to the more energetically favorable position between the alpha and beta carbons of the propyl side chain. Thus isosafrole, a propenylbenzene, is born. 

What happens during hydrolysis is that the OH forms and the elemicin propyl alcohol drops out of solution and forms its own oil layer. Of course one won t see this because the solution is a big old brown mess, lousy with emulsion particles. Emulsions suck But can be dealt with effectively by adding a little acid or base, or filtration and the like. Anyway, after a little work up one gets some really pure phenylpropyl compound. And if Strike had Strike s way. Strike would have that OH stuck right on the middle (beta) carbon of the species. Work could then progress on using that OH to get an amphetamine (Sob Strike had so much about that subject that Strike was prepared to put in this book ). 

The basic premise for making bromosafrole has been to mix sa-frole with Hydrobromic Acid (a.k.a. hydrogen bromide, HBr). That s it. The HBr does what is called a Markovnikov addition reaction whereby the HBr sees the allyl double bond of safrole and preferentially attaches its hydrogen to the gamma carbon and its bromine to the middle beta carbon (don t ask). 

The problem really isn t the concentration of the HBr, but rather is the result of the HBr being in water. As long as there is a significant amount of water present in the reaction mix with safrole, that water is going to compete with bromine for that juicy beta carbon on safrole. And it s gonna win, too. The answer is to use non-aqueous HBr solutions. 

For the past year Strike had been in consultation with contract labs over the making of phenylisopropyl alcohols using sulfuric acid and allylbenzenes (don t ask). The lab owners would listen patiently as Strike primitively described how and why an OH should go on the beta carbon. And without exception, the lab owners would point out to Strike that the best way to get an OH on the beta carbon would be to put a Br there first. But Strike don t wanna put a Br there first Strike would say, Strike wants the OH put on directly using sulfuric acid " The lab guys had to do what Strike said because Strike was holding all the money (...a fool and her money etc.). But out of curiosity Strike asked how they would get that Br on the beta carbon. Every one of them said it was simply a matter of using the 48% HBr in acetic acid. They even showed Strike their stock solutions (usually from Aldrich or Fisher). 

METHOD 3 This is not really a method. It is more of an idea Strike and others have been toying with. Eleusis had been supporting the idea that one could make use of the common 48% aq HBr if one employed the technique of dehydration . We remember that the water was competing with the Br in the normal 48% solution. But the literature demonstrates that in conditions such as this, a competing acid can strip away the water (dehydrate) from the beta carbon allowing the Br a second chance to pop in. 

So without direct amination we are confined to semi-direct ami-nation (Strike s terminology). In Strike s opinion, the direct addition of an azide (N3) counts. Once on the beta carbon, that azide is as good as an amine. But can we get an azide directly onto safrole without having to go thru the bromosafrole intermediate as was discussed earlier Maybe we can ... 

The next method Strike has for semi-direct amination is really weird, Strike is really exposing Strike s ignorance of chemistry with this dog. But if one looks hard at the articles cited, the potential is there. The authors came up with this little procedure that produced vicinal diamines out of alkenes [83]. Later they found that if they did a couple of things different, they would end up with a monoamine with the majority product being at the beta carbon. The following is a conjoining of the two paper s experimentals ... 

The LUMO of phenylethylene also has most density at the terminal (beta) carbon, so that these two atoms attach to each other, yielding the sterically unfavorable product. 

In rats and mice, TBT compounds are hydroxylated by microsomal monooxygenase attack (see Environmental Health Criteria 116). Hydroxylation can occur on either the alpha or beta carbon of the butyl group, that is, alpha or beta in relation to the Sn atom (see Figure 8.5). After hydroxylation, the hydroxylated moiety breaks away to leave behind dibutyltin. 

I), the substituent occurs on the carbon atom bearing the unpaired electron, and in this position it is able to provide resonance structures in which the unpaired electron appears on the substituent. The substituent consequently has the effect of stabilizing the radical, the extent of such stabilization depending, of course, on the capacity of the substituent for resonance. In product radical (II), the substituent is situated on the beta carbon atom, where it is unavailable for participation in resonating structures involving the odd electron. Consequently, the product radical (I) ordinarily will be more stable than... 

The alkyl halide used with the alkynide anion must be methyl or primary and also unbranched at its second (beta) carbon. 

Alkyl halides that are 2° or 3°, or are 1° with branching at the beta carbon, undergo elimination reaction predominantly. 

Olefin formation also occurs when the alpha carbon (the one attached to -X the beta carbon is one position removed from alpha) is a secondary or tertiary alkyl carbon and more especially when an alpha-phenyl or alpha-vinyl group is present. 83 Whereas these olefin-forming reactions frequently do not require the presence of an added base, some reactions are accelerated by a base. The latter base-accelerated reactions came to be designated E2, in contrast to El reactions.84... 

When Schiff s bases (242), derived from ketones and tm-butylamine, were reacted with dimethyl methoxymethylenemalonate in diphenyl ether at 80-130°C for 1-15 hr, then at 190-250°C for 1-3 hr, 2-hydroxy-3-pyridinecarboxylates (243) were obtained by a one-pot procedure. In the first step of the reaction, the beta-carbon of the enamine moiety was involved instead of the amino group (89JHC773). 

Keto ester 67 was converted to the unsaturated nitrile 70 in a routine manner. The latter proved to be an exceptionally useful intermediate. Concern that the significant steric demands which are associated with the formation of a sigma bond to the fully substituted beta carbon of the unsaturated nitrile would prevent reaction from occurring, were allayed by the discovery that the controlled potential reduction of 70 at —2.4 V in the presence of dimethyl malonate as the proton donor, alforded a 90% isolated yield of the requisite [3.2.1] adduct 71. This material was subsequently converted to enone 72 [42], a convergent point with an existing synthesis of quadrone (59). 

The three-dimensional structure of rat liver metallothionein containing five Cd2+ and two Zn2+ ions is shown in the accompanying stereoscopic diagram.1 The 61 alpha carbons, the beta carbon and sulfur atoms (green) of cysteine residues and the bound metal ions are indicated. 

Neopemrl Polyol Esters. These polyesters are prepared by the esterification of. -carbon polyfunclional alcohols with mono-lunctional acids. Because the beta carbon of the starting alcohol does not contain hydrogen, these esters are superior in thermal stability to the diesters. Most of the oilier characteristics arc similar to those of the dicsters. As a result of their superior stability, the neopentyl esters are finding increasing use as the luhricuni for aircraft turbine engines. 

The benzylamine counterpart (as if one were to move the amine function from the beta-carbon to the alpha-carbon of the three carbon chain of the amphetamine molecule) is alpha-ethyl-3,4-methylenedioxybenzylamine or l-amino-l-(3,4-methylenedioxyphenyl)propane, ALPHA. The hydrochloride salt has a mp of 199-201 °C. At low threshold levels (10 milligram area) there were eyes-closed dreams with some body tingling. The compound was not anorexic at any dose (up to 140 milligrams) and was reported to produce a pleasant, positive feeling. It is very short-lived (about 3 hours). The N-methyl homologue is alpha-ethyl-N-methyl-3,4-methylenedioxybenzylamine or 1 -methylamino-1 -(3,4-methylenedioxy-phenyl)propane, M-ALPHA. It is similar in action, but is perhaps twice as potent (a plus one or plus two dose is 60 milligrams) and of twice the duration,... 

Regions that cannot be aligned with sequence are often built with polyala-nine, reflecting our knowledge that all amino acids contain the same backbone atoms, and all but one, glycine, have at least a beta carbon (Plate 11). In this manner, we build as many atoms into the model as possible in the face of our ignorance about how to align the sequence with the map in certain areas. 

The high electron density in the double bond system of ethylenes makes nucleophilic attack unfavorable unless the system is substituted with one or more electron withdrawing groups such as -N02, -CN, -COR. When these substituents are present, attack by alcohols or alkoxide ions occurs at the beta-carbon predominantly. For example, researchers have found (12) that sodium methoxide or sodium ethoxide added rapidly at room temperature to beta-nitrostyrene leads to the alkoxide formation of the derivative (Reaction VIII). This reaction is generally not only for arylnitroalkenes (13) but also for other activated double bonds (14). Another example of alcohol addition to an activated double bond includes the reaction of alcohols with acrylonitrile to produce a cyano-ethylated ether (14A). 

In general, the "addition-elimination mechanism will be favored for compounds with low electron density on the beta-carbon, while the "elimination-addition" pathway will be favored by cis-isomers where there is a good chance of eliminating the elements of HX from a trans-position. 

---