Archive for the 'Uncategorized' Category

History of the development of ChemDraw

I suspect that the majority of my readers have no experience in drawing chemical structures by hand for publication purposes. That’s because of one software product: ChemDraw. I remember using the Fieser triangle (unfortunately no longer sold by Aldrich – click to see a pic and product description!), a plastic template that had standard-sized rings, like nice pentagons and hexagons, and chair and boat conformations of cyclohaxane, and you’d take your fancy ink pen and careful follow the template. Then you moved the template to draw say a bond off of the ring and hoped to god that the ink didn’t smudge. There were other templates for drawing letters and numbers – or you used scratch-off transfer decals. (By this point all of you under 40 are thinking “what the hell is he talking about?”)

Well all of that changed with three seminal events for organic chemists: the introduction of the original Macintosh computer, the introduction of the Apple LaserWriter and the introduction of ChemDraw. The Mac allowed one to sketch in a much more intuitive way – again for those less than 50, computers use to come without a mouse! Imagine trying to draw a chemical structure using a keyboard. That’s why there were no structure drawing tools prior to the Mac. The LaserWriter meant that you could print an output that looked as good as what you had on the screen, and could thus be submitted for publication. And ChemDraw – well this was just astonishing! I still remember the day during my post-doc when the Mac and LaserWriter arrived and we launched ChemDraw and were able to quickly draw molecules – steroid, and conformations, and stereoisomers and they all looked beautiful and we could get them done in a flash!

When I started my first academic position at Northern Illinois University in August 1987 I purchased a Mac and a LaserWriter and ChemDraw as part of my start-up – and I was the first in the department to have a Mac – but that changed rapidly!

So, why all of the teary reminiscences? Well David Evans has just published1 a nice romp through the mid-1980s recalling how Stewart Rubinstein, aided by Evans and his wife, developed ChemDraw and started CambridgeSoft, and as Stuart Schreiber says “ChemDraw changed the field in a way that has not been replicated since.”

Today, there are other chemical structure drawing tools available, and in fact I no longer use ChemDraw, but it is still a wonder to be able to create drawings so easily and so nicely. Maybe one day I’ll reminisce about the day I got EndNote and my life changed again!

References

1) Evans, D. A. “History of the Harvard ChemDraw Project,” Angew. Chem. Int. Ed. 2014, 53, 1521-3773, DOI 10.1002/anie.201405820.

Uncategorized Steven Bachrach 08 Oct 2014 3 Comments

Splitting CO2 with a two-coordinate boron cation

This paper is a bit afield from the usual material I cover but this is an interesting reaction. Shoji and coworkers have prepared the two-coordinate boron species 1,1 and confirmed its geometry by an x-ray crystal structure. What I find interesting is its reaction with CO2, which gives 2 and organoboranes that are not identified, though presumably derived from 3.

M06-2x/6-311+G(d,p) computations support a hypothetical mechanism whereby first a complex between 1 and CO2 is formed (CP1), that is 4.4 kcal mol-1 above isolated reactants. Then passing through TS1, which is 4.2 kcal mol-1 above CP1, an intermediate is formed (INT), which is almost 6 kcal mol-1 below starting materials. A second transition state is then traversed (about 1 kcal mol-1 below starting materials), to form an exit complex between 2 and 3, which can then separate to the final products with an overall exothermicity of 10.6 kcal mol-1. The structures of these critical points are shown in Figure 1.

1
(0.0)

CP1
(4.4)

TS1
(8.6)

INT
(-5.7)

TS2
(-1.1)

CP2
(-9.0)

Figure 1. M06-2x/6-311+G(d,p) optimized structures. Relative energy in kcal mol-1.

References

(1) Shoji, Y.; Tanaka, N.; Mikami, K.; Uchiyama, M.; Fukushima, T. "A two-coordinate boron cation featuring C–B+–C bonding," Nat. Chem. 2014, 6, 498-503, DOI: 10.1038/nchem.1948.

InChIs

1: InChI=1S/C18H22B/c1-11-7-13(3)17(14(4)8-11)19-18-15(5)9-12(2)10-16(18)6/h7-10H,1-6H3/q+1
InChIKey=WLUJABFTLHAEMI-UHFFFAOYSA-N

2: InChI=1S/C10H11O/c1-7-4-8(2)10(6-11)9(3)5-7/h4-5H,1-3H3/q+1
InChIKey=CUJVTHUIQVMVHD-UHFFFAOYSA-N

3: InChI=1S/C9H11BO/c1-6-4-7(2)9(10-11)8(3)5-6/h4-5H,1-3H3
InChIKey=ZJKBFARYTPYYGV-UHFFFAOYSA-N

Uncategorized Steven Bachrach 04 Aug 2014 1 Comment

[2,2]paracyclophane – structure resolved

The structure of [2,2]paracyclophane 1 has been somewhat controversial for some time. Early x-ray structures indicated that the molecule was quite symmetric, D2h with the phenyl rings and the ethyl bridges eclipsed. Subsequent low-T experiments suggested a lower symmetry form D2 with a twist that relieves some of the unfavorable eclipsing interactions in the ethano bridges. High-level computations by Grimme1 and then some by myself2 indicated that the D2 structure is the lowest energy conformation, with however a low barrier through the D2h structure.

The suggestion of the D2 minimum was vehemently criticized by Dodziuk, et al. on the basis of NMR analysis.3

Now, a low temperature x-ray experiment of 1 brings clarity to the situation.4 (The introduction provides a nice summary of the previous 70 year history regarding the structure of 1.) At temperatures below 45 K, 1 is found as a single structure of D2 symmetry (with space group P4n2). The structure is shown in Figure 1. A phase change occurs at about 45 K, and above 60 K the crystal has P42/mnm symmetry. The structure of 1 at the high temperature appears as D2h with somewhat broader thermal motion of the ethano carbons than the phenyl carbons. The low T structure is in excellent accord with the previous theoretical studies, and the phase transition helps bring into accord all of the previous x-ray crystallographic work.

Figure 1. X-ray structure at 15K of 1.

References

(1) Grimme, S. "On the Importance of Electron Correlation Effects for the π-π Interactions in Cyclophanes," Chemistry Eur. J. 2004, 10, 3423-3429, DOI: 10.1002/chem.200400091.

(2) Bachrach, S. M. "DFT Study of [2.2]-, [3.3]-, and [4.4]Paracyclophanes: Strain Energy, Conformations, and Rotational Barriers," J. Phys. Chem. A 2011, 115, 2396-2401, DOI: 10.1021/jp111523u.

(3) Dodziuk, H.; Szymański, S.; Jaźwiński, J.; Ostrowski, M.; Demissie, T. B.; Ruud, K.; Kuś, P.; Hopf, H.; Lin, S.-T. "Structure and NMR Spectra of Some [2.2]Paracyclophanes. The Dilemma of [2.2]Paracyclophane Symmetry," J. Phys. Chem. A 2011, 115, 10638-10649, DOI: 10.1021/jp205693a.

(4) Wolf, H.; Leusser, D.; R. V. Jørgensen, M.; Herbst-Irmer, R.; Chen, Y.-S.; Scheidt, E.-W.; Scherer, W.; Iversen, B. B.; Stalke, D. "Phase Transition of [2,2]-Paracyclophane – An End to an Apparently Endless Story," Chem. Eur. J. 2014, 20, 7048–7053, DOI: 10.1002/chem.201304972.

InChIs

1: InChI=1S/C16H16/c1-2-14-4-3-13(1)9-10-15-5-7-16(8-6-15)12-11-14/h1-8H,9-12H2
InChIKey=OOLUVSIJOMLOCB-UHFFFAOYSA-N

Uncategorized Steven Bachrach 28 May 2014 2 Comments

Extremely short non-bonding HH distance

What is the closest non-bonding HH distance within a single molecule? The world record had been 1.617 Å in a pentacyclodecane.1 This record now appears to be broken by the preparation of the disilane 1.2 The 1H NMR and IR suggest the interior hydrogens are very close. The x-ray structure of 1 indicates a very short Si-Si distance of 4.433 Å, a distance that must accommodate two S-H bonds, typically about 1.48 Å and the HH non-bonded distance, which might be as short then as 1.47 Å! The crystal is unfortunately not large enough for a neutron diffraction study, which would enable precise location of the hydrogens.


1

However, computations can help here, and they suggest a HH separation of only 1.57 Å: this is the distance obtained with B3PW91/6-311+G(2d,p), M062x/6-311+G(2d,p) and MP2/6-31G(d). The M062x/6-311+G(2d,p) structure is shown in Figure 1.

Figure 1. The M062x/6-311+G(2d,p) optimized structure of 1.

Any ideas for a compound with an even shorter non-bonded HH distance?

References

(1) Ermer, O.; Mason, S. A.; Anet, F. A. L.; Miura, S. S. "Ultrashort nonbonded hydrogenhydrogen distance in a half-cage pentacyclododecane," J. Am. Chem. Soc. 1985, 107, 2330-2334, DOI: 10.1021/ja00294a023.

(2) Zong, J.; Mague, J. T.; Pascal, R. A. "Exceptional Steric Congestion in an in,in-Bis(hydrosilane)," J. Am. Chem. Soc. 2013, 135, 13235-13237, DOI: 10.1021/ja407398w.

InChI

1: InChI=1S/C39H32S3Si2/c1-7-19-34-28(13-1)25-40-31-16-4-10-22-37(31)44-38-23-11-5-17-32(38)41-26-29-14-2-8-20-35(29)43(34)36-21-9-3-15-30(36)27-42-33-18-6-12-24-39(33)44/h1-24,43-44H,25-27H2
InChIKey=SBEUQCUCKCNPCC-UHFFFAOYSA-N

Uncategorized Steven Bachrach 01 Oct 2013 12 Comments

thiourea-catalyzed hydroamination

Jacobsen reports on another application of thiourea-based organocatalysts, this time for the
catalysis of hydroamination.1 To support the synthetic effort, he examined the uncatalyzed intramolecular hydroamination that takes 1, through TS1 into product 2. The geometry of TS1 optimized at B3LYP/6-31+G(d,p) is shown in Figure 1. The computed barrier for this reaction is 22.2 kcal mol-1. Using a model thiourea as the catalyst (MeHN)2C=S, 3), Jacobsen locates a
catalyzed transition state TS2 shown in Figure 1. The activation barrier for this catalyzed reaction is 19.1 kcal mol-1, suggesting that a thiourea can afford a real catalytic effect.

TS1

TS2

Figure 1. B3LYP/6-31+G(d,p) optimized geometries of TS1 and TS2(the catalyzed transition state).

Jacobsen then goes on to show that 4 can act as both an excellent catalyst for the hydroamination reaction along with inducing significant enantioselectivity. An example is Reaction 1, where 10 mol% of catalyst 3 gives an overall yield of 83% and an ee of 91%, while in the absence of catalyst the yield is only 8%.

References

(1) Brown, A. R.; Uyeda, C.; Brotherton, C. A.; Jacobsen, E. N. "Enantioselective Thiourea-Catalyzed Intramolecular Cope-Type Hydroamination," J. Am. Chem. Soc. 2013, 135, 6747-6749, DOI: 10.1021/ja402893z.

InChIs

1: InChI=1S/C5H11NO/c1-2-3-4-5-6-7/h2,6-7H,1,3-5H2
InChIKey=JUMXQRNWLGIKEI-UHFFFAOYSA-N

2: InChI=1S/C5H11NO/c1-5-3-2-4-6(5)7/h5,7H,2-4H2,1H3
InChIKey=YVBPNYXAQNAMLH-UHFFFAOYSA-N

3: InChI=1S/C3H8N2S/c1-4-3(6)5-2/h1-2H3,(H2,4,5,6)
InChIKey=VLCDUOXHFNUCKK-UHFFFAOYSA-N

4: InChI=1S/C44H49N3OS/c1-44(2,3)42(41(48)36-25-15-24-35(36)34-23-14-21-30-16-10-11-22-33(30)34)46-43(49)45-37-26-12-13-27-40(37)47-38(31-17-6-4-7-18-31)28-29-39(47)32-19-8-5-9-20-32/h4-11,14,16-23,28-29,35-37,40,42H,12-13,15,24-27H2,1-3H3,(H2,45,46,49)/t35-,36?,37-,40-,42-/m1/s1
InChIKey=OJMZMPGOFWBKAF-FDGFXIECSA-N

Uncategorized Steven Bachrach 10 Jul 2013 No Comments

Second edition of Computational Organic Chemistry

After much delay, the second edition of my book Computational Organic Chemistry has been sent off to the publisher! This edition is an update from the first, including many new examples of the major themes covered in the first edition. In addition there are some entirely new sections and chapters, extending the scope of the book into areas not mentioned in the first edition. There are also some new interviews of major players in the field. Comments from this blog where helpful in guiding my choices for what new materials to include in the book.

I suspect that editing of the book and making it all ready for print will take through the rest of the year. Later on this year I will discuss in the blog the new features of the book in some detail.

I intend to continue to blog on new papers through the publication of the second edition and beyond. So continue to monitor this blog for new papers and for information on where and when to purchase the second edition!

Uncategorized Steven Bachrach 10 Jun 2013 6 Comments

Covalently linked cycloparaphenylenes – onwards to nanotubes

Nanotubes are currently constructed in ways that offer little control of their size and chirality. The recent synthesis of cycloparaphenylenes (CPP) provides some hope that fully controlled synthesis of nanotubes might be possible in the near future. Jasti has now made an important step forward in preparing dimers of CPP such as 1.1


1


2

They also performed B3LYP-D/6-31G(d,p) computations on 1 and the directly linked dimer 2. The optimized geometries of these two compounds in their cis and trans conformations are shown in Figure 1. Interestingly, both compounds prefer to be in the cis conformation; cis-1 is 10 kcal mol-1 more stable than trans-1 and cis-2 is 30 kcal mol-1 more stable than the trans isomer. While a true transition state interconnecting the two isomers was not located, a series of constrained optimizations to map out a reaction surface suggests that the
barrier for 1 is about 13 kcal mol-1. The authors supply an interesting movie of this pseudo-reaction path (download the movie).

cis-1

trans-1

cis-2

trans-2

Figure 1. B3LYP-D/6-31G(d,p) optimized geometries of the cis and trans conformers of 1 and 2. (Be sure to click on these images to launch a 3-D viewer; these structures come to life in 3-D!)

References

(1) Xia, J.; Golder, M. R.; Foster, M. E.; Wong, B. M.; Jasti, R. "Synthesis, Characterization, and Computational Studies of Cycloparaphenylene Dimers," J. Am. Chem. Soc. 2012, 134, 19709-19715, DOI: 10.1021/ja307373r.

InChIs

1: InChI=1S/C106H82/c1-5-13-79-21-9-17-76-29-37-85(38-30-76)95-59-63-98(64-60-95)103-71-69-101(82(16-8-4)24-12-20-77-27-35-84(36-28-77)90-51-55-94(56-52-90)91-45-41-86(79)42-46-91)73-105(103)99-65-67-100(68-66-99)106-74-102-70-72-104(106)97-61-57-88(58-62-97)81(15-7-3)23-10-18-75-25-33-83(34-26-75)89-49-53-93(54-50-89)92-47-43-87(44-48-92)80(14-6-2)22-11-19-78-31-39-96(102)40-32-78/h5-16,21-74H,1-4,17-20H2/b21-9-,22-11-,23-10-,24-12-,79-13+,80-14+,81-15+,82-16+
InChIKey=WFVBBCVHFBTQRK-VPGVYKRGSA-N

2: InChI=1S/C100H78/c1-5-13-75-21-9-17-72-29-37-81(38-30-72)91-59-63-94(64-60-91)97-67-65-95(78(16-8-4)24-12-20-73-27-35-80(36-28-73)86-51-55-90(56-52-86)87-45-41-82(75)42-46-87)69-99(97)100-70-96-66-68-98(100)93-61-57-84(58-62-93)77(15-7-3)23-10-18-71-25-33-79(34-26-71)85-49-53-89(54-50-85)88-47-43-83(44-48-88)76(14-6-2)22-11-19-74-31-39-92(96)40-32-74/h5-16,21-70H,1-4,17-20H2/b21-9-,22-11-,23-10-,24-12-,75-13+,76-14+,77-15+,78-16+
InChIKey=HOODCSIDKUJYKE-XJQPCHFNSA-N

Uncategorized Steven Bachrach 22 Jan 2013 No Comments

Long C-O bonds

I have written a number of posts discussing long C-C bonds (here and here). What about very long bonds between carbon and a heteroatom? Well, Mascal and co-workers1 have computed the structures of some oxonium cations that express some very long C-O bonds. The champion, computed at MP2/6-31+G**, is the oxatriquinane 1, whose C-O bond is predicted to be 1.602 Å! (It is rather disappointing that the optimized structures are not included in the supporting materials!) The long bond is attributed not to dispersion forces, as in the very long C-C bonds (see the other posts), but rather to σ(C-H) or σ(C-C) donation into the σ*(C-O) orbital.


1

Inspired by these computations, they went ahead and synthesized 1 and some related species. They were able to get crystals of 1 as a (CHB11Cl11)- salt. The experimental C-O bond lengths for the x-ray crystal study are 1.591, 1.593, and 1.622 Å, confirming the computational prediction of long C-O bonds.

As an aside, they also noted many examples of very long C-O distances within the Cambridge
Structural database that are erroneous – a cautionary note to anyone making use of this database to identify unusual structures.

References

(1) Gunbas, G.; Hafezi, N.; Sheppard, W. L.; Olmstead, M. M.; Stoyanova, I. V.; Tham, F. S.; Meyer, M. P.; Mascal, M. "Extreme oxatriquinanes and a record C–O bond length," Nat. Chem. 2012, 4, 1018-1023, DOI: 10.1038/nchem.1502

InChIs

1: InChI=1S/C21H39O/c1-16(2,3)19-10-12-20(17(4,5)6)14-15-21(13-11-19,22(19)20)18(7,8)9/h10-15H2,1-9H3/q+1/t19-,20+,21-
InChIKey=VTBHIDVLNISMTR-WKCHPHFGSA-N

Uncategorized Steven Bachrach 07 Jan 2013 1 Comment

The longest straight chain alkane

The role of dispersion in understanding organic chemistry, both structure and reactivity, is truly coming into prominence (see for example this blog post for a compound whose stability is the result of dispersion). This has been driven in part by new computational techniques to properly account for dispersion. An interesting recent example is the structure of long chain alkanes, with a question posed and answered by Mata and Suhm:1 What is the largest alkane whose most stable conformation is the extended chain?

The question is attacked by computation and experiment. The computational methodology involves corrections to the local MP2-F12 energy involving the separation of orbital pairs that are treated with a coupled clusters method. The straight chain (having only anti arrangements about the C-C bonds) and the hairpin conformer (having three gauche arrangements) were completely optimized. The C17H36 hairpin isomer is shown in Figure 1. For chains with 16 or fewer carbons, the all-anti straight chain is lower in energy, but for chains with 17 or more carbon atoms, the hairpin is lower in energy. Gas-phase low temperature IR and Raman spectra suggest that dominance of the hairpin occurs when the chain has 18 carbons, though careful analysis suggests that this is likely an upper bound. At least tentatively the answer to the question is that heptadecane is likely the longest alkane with a straight chain, but further lower temperature experiments are needed to see if the C16 chain might fold as well.

Figure 1. Optimized geometry of the hairpin conformation of heptadecane.

(I thank Dr. Peter Schreiner for bringing this paper to my attention.)

References

(1) Lüttschwager, N. O. B.; Wassermann, T. N.; Mata, R. A.; Suhm, M. A. "The Last Globally Stable Extended Alkane," Angew. Chem. Int. Ed. 2012, ASAP, DOI: 10.1002/anie.201202894.

InChIs

Heptadecane: InChI=1S/C17H36/c1-3-5-7-9-11-13-15-17-16-14-12-10-8-6-4-2/h3-17H2,1-2H3
InChIKey=NDJKXXJCMXVBJW-UHFFFAOYSA-N

Uncategorized Steven Bachrach 10 Sep 2012 3 Comments

Structure of 1-Methyl-Piperidone

The combined supersonic jet expansion and Fourier transform microwave spectroscopy provides an excellent opportunity for the synergistic workings of experiments and computations. This is nicely demonstrated in the study of 1-methyl-4-piperidone.1

The careful microwave study allows for the full structural characterization of the equatorial form 1e along with obtaining a good deal of information concerning the axial form 1a. To help evaluate the experimental data, the authors have optimized the structure of the two isomers at MP2, B3LYP and M06-2x using the 6-311++G(d,p) basis set.

The rotational parameters computed with the three methods are in very fine agreement with the experimental values. Of particular note is that the three computations predict a different sign for the nuclear quadrupole coupling tensor elements χaa and χbb, and this is observed in the experiment as well. It is perhaps the critical identifier of the axial isomer. The computed and experimental geometries of 1e are in fine agreement, with the largest deviation of a few degrees in the dihedral angle of the carbonyl to the ring. The experiment suggests an energy difference of 11.9 kJ mol-1, which is corroborated by MP2, B3LYP and M06-2x computations. In fact, these first two methods predict an enthalpy difference within a kJ of the experimental value.

References

(1) Evangelisti, L.; Lesarri, A.; Jahn, M. K.; Cocinero, E. J.; Caminati, W.; Grabow, J.-U., "N-Methyl Inversion and Structure of Six-Membered Heterocyclic Rings: Rotational Spectrum of 1-Methyl-4-piperidone," J. Phys. Chem. A, 2011,
115, 9545–9551, DOI: 10.1021/jp112425w

InChIs

1: InChI=1/C6H11NO/c1-7-4-2-6(8)3-5-7/h2-5H2,1H3
InChIKey=HUUPVABNAQUEJW-UHFFFAOYAT

Uncategorized Steven Bachrach 20 Sep 2011 No Comments

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