Molecules acyclic

Simple hydrocarbons represent rather well-behaved extensions of the conformational principles illustrated previously in the analysis of rotational equilibria in ethane and n-butane. The staggered conformations correspond to potential energy minima, the eclipsed conformations to potential energy maxima. Of the staggered conformations, anti forms are more stable than gauche. The magnitudes of the barriers to rotation of many small organic molecules have been measured. Some representative examples are listed in Table 3.3. The experimental techniques used to study rotational isomerism include microwave spectroscopy, electron diffraction, ultrasonic absorption, and infrared spectroscopy.  

See reference 1(a) (p. 72) for an extensive list of references to published applications. 

Methods for determination of rotational barriers are described in reference 10 and by E. Wyn-Jones and R. A. Pethrick, Top. Stereochem. 5, 205 (1969). 

The rotational barrier in methylsilane (Table 3.3, entry 5) is significantly smaller than that of ethane (1.7 versus 2.88 kcal/mol), probably because of decreased internuclear repulsions resulting from the longer silicon-carbon bond length of 1.87 A, compared to 1.54 A for ethane. 

The haloethanes all have similar rotational barriers of 3.2-3.7 kcal/mol. The increase in the barrier height relative to ethane is thought to be a van der Waals repulsion effect. The heavier halogens have larger van der Waals radii, but also longer bond lengths, so that the net effect is relatively constant for all the halogens. 

2-dimethylpropane, in which the barrier is 4.7 kcal/mol, is 1.8 kcal/mol for the total of three methyl-hydrogen eclipsing interactions. 

Rotational isomerism about the C(2)-C(3) single bond of terminal alkenes offers an interesting contrast to the examples we have discussed to this point. The case of 1-butene is illustrative. The conformations to be considered are as follows  

The conformations of simple hydrocarbons can be interpreted by extensions of the principles illustrated in the analysis of rotational equilibria in ethane and butane. The staggered 

KutMtocul barrier increases with ihe number of CH3/H eclipsing interactions. 

Changing the atom bound to a methyl group from carbon to nitrogen to oxygen, as in going from ethane to methylamine to methanol, produces a decrease in the rotational barrier from 2.88 to 1.98 to 1.07kcal/mol. This closely approximates the 3 2 1 ratio of the number of H—H eclipsing interactions in these three molecules. 

These energy barriers can be quantified in terms of enthalpy (H°), so it is possible to calculate the energy of a given rotamer and the relative population of that rotamer. For butane the calculation must also include  

When heteroatoms are added to the chain, the size of the atom plays a role, just as the size of an attached group is important. In addition to this, however, the nonbonded electrons on those heteroatoms interact to influence the rotamer population relative to simple alkanes. In anf(-l,2-dichloroethane (148), the chlorine 

Another way to stabilize an eclipsed or gauche conformation is to coordinate heteroatom substituents with a metal ion via chelation. Oishi and co-workers reduction of 153 with zinc borohydride proceeds via a chelated species, 154. 2 Chelation of zinc to the hydroxyl and carbonyl groups effectively locks the conformation into that shown in the transition state required for reaction. The methyl and hydrogen are held in place, and the hydride is delivered from the less hindered face (over the hydrogen in 154) to complete the reaction (see secs. 4.4.B and 4.7.B). Since transition metal salts usually behave as Lewis acids, the presence of a heteroatom with 

10 Nitrogen Oligomers and Polymers Superfuels or Chimeras NXs + SMesSiNs N(Ns)3 + SMcsSiX 

Computations on C(N3 4 have been reported [109], The salt [C(N3)3 ][SbCl6 ] was made by the reaction 

Other organic molecules with a very high nitrogen content have been synthesized, e.g. 3,6-diazido-l,2,4,5-tetrazine, 22  

Butler et al. have recently reported that in a revision of their approach, isotopic labeling proved unequivocally that HN5 and/or NJ was formed in solution R. N. Butler, J. M. Hannifify, J. C. Stephens, L. A. Burke, J. Org. Chem., 2008, 73, 1354. 

This paper begins with a nice short summary of hexaazabenzene work up to the time. 

Allinger and Y. H. Yuh, MM2, No. 395, Quantum Chemistry Exchange, Chemistry Department, University of Indiana, Bloomington, Indiana A variety of computer programs for energy minimization are also available from commercial sources. 

1 (1968) barriers are those for rotation about the bond indicated in the formula. 

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Fig. 9.7 A pseudo-acyclic molecule is generated by breaking the ring.

A particular advantage of the low-mode search is that it can be applied to botli cyclic ajic acyclic molecules without any need for special ring closure treatments. As the low-mod> search proceeds a series of conformations is generated which themselves can act as starting points for normal mode analysis and deformation. In a sense, the approach is a system ati( one, bounded by the number of low-frequency modes that are selected. An extension of th( technique involves searching random mixtures of the low-frequency eigenvectors using Monte Carlo procedure. 

The accessibility of the +4 and +6 oxidation states for sulfur and, to a lesser extent, selenium gives rise to both acyclic and cyclic molecules that have no parallels in N-O chemistry. Thus there is an extensive chemistry of chalcogen diimides RN=E=NR (E = S, Se, Te) (Section 10.4). In the case of Te these unsaturated molecules form dimeric structures reflecting the increasing reluctance for the heavier chalcogens to form multiple bonds to nitrogen. The acyclic molecule N=Sp3,... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Two simple acyclic molecules are transformed mto a smgle tncyclic compound bearing four conoguons stereogenic centers m high yield ... 

The synthetic challenge is now reduced to the preparation of intermediates 2-4. Although intermediates 3 and 4 could potentially be derived in short order from very simple precursors (see Scheme 4), intermediate 2 is rather complex, particularly with respect to stereochemistry. Through a short sequence of conventional functional group manipulations, it is conceivable that aldehyde 2 could be derived from intermediate 9. Hydrolysis and keta-lization reactions could then permit the formation of 9 from intermediate 11, the cyclic hemiaminal of the highly stereo-defined acyclic molecule, intermediate 12. 

An acyclic molecule has more entropy than a similar cyclic molecule because there are more conformations (cf. hexane and cyclohexane). Ring opening therefore means a gain in entropy and ring closing a loss. 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

In this section we focus on intramolecular functionalization. Such reactions normally achieve selectivity on the basis of proximity of the reacting centers. In acyclic molecules, intramolecular functionalization normally involves hydrogen atom abstraction via a six-membered cyclic TS. The net result is introduction of functionality at the S-atom in relation to the radical site. 

All these 3,4-dihydro-2H-1 -benzopyran-2-ones 17 and 18 are substrates of class A and class C (3-lactamases. They are thus the first 8-lactones that are hydrolyzed by [3-lactamases. The kcat values for these substrates are generally smaller than those of the analogous acyclic phenaceturates suggesting that the tethered leaving group obstructs the attack of water on the acyl-enzyme. Despite the apparent advantage of the long-lived acyl-enzymes, the irreversible inhibition by the functionalized compounds is no better than that of acyclic molecules 16. Thus, even the tethered QM cannot efficiently trap a second nucleophile at the [3-lactamase active site, at least as placed as dictated by the structure of compounds 18.70... 

P2X Z = 2 Dx = 1.59 R = 0.11 for 881 intensities. The acyclic molecule has the planar, zigzag conformation. The terminal OH and N-OH groups are +syn and ap, respectively. There is an interesting system of O-H N hydrogen-bonds which forms a spiral along the screw-axis. Only seven of the hydrogen atoms were located. 

Two simple acyclic molecules are transformed into a single tricyclic compound bearing four contiguous stereogenic centers in high yield.177... 

Decius JC (1948) A tabulation of general formulas for inverse kinetic energy matrix elements in acyclic molecules. J Chem Phys 16 1025-1034... 

Our discussions of the basicity of organic nitrogen compounds have concentrated predominantly on simple amines in which the nitrogen atom under consideration is part of an acyclic molecule. Many biologically important compounds, and especially drug molecules, are based upon systems in which nitrogen is part of a heterocycle. We shall consider the... 

Hirshfeld (1964) pointed out that bond bending not only occurs in ring systems, but also results from steric repulsions between two atoms two bonds apart, referred to as 1-3 interactions. The effect is illustrated in Fig. 12.3. The atoms labeled A and A are displaced from the orbital axes, indicated by the broken lines, because of 1-3 repulsion. As a result, the bonds defined by the orbital axes are bent inwards relative to the internuclear vectors. When one of the substituents is a methyl group, as in methanol [Fig. 12.3(b)], the methyl-carbon-atom hybrid reorients such as to maximize overlap in the X—C bond. This results in noncolinearity of the X—C internuclear vector and the three-fold symmetry axis of the methyl group. Structural evidence for such bond bending in acyclic molecules is abundant. Similarly, in phenols such as p-nitrophenol (Hirshfeld... 

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