[AmbitiousStudent]

I got some questions I need some help with. I had started but I feels that I am a little bit struck and would be glad if you can help me with the answers and also some explanation why.

Busulfan (figure below) is a di-ester out of 1,4 butanediol with Methanesulfonic acid

Busulfan

Busulfan can be more water soluble if it can create a complex with BCD(Figure below)

BCD

The figure shows that BCD has to carbohydrate tails that are connected with a heterocyclic carbon compound.

Part 1. Which of these two components in BCD can be expected to increase the water soluble?

I guess it is the OH-group according to the “rule” similar soluble similar. Correct?

Part 2 The complex between BCD and busulfan I not covalent. The figure shows which parts of BCD that actively contribute to the creation of the busulfan-complex.

Which type of intermolecular interaction between BCD and busulfan can be expected to be most important?

BCD+Busulfan

I guess it is hydrogen bonds, is that correct?

Part 3 Busulfan is an important reagent in some covalent reaction because of methane sulfur anion CH3SO3- is a very good leaving group.

Which substation product can be expected if busulfan is allowed to react with a surplus of NaCH3CH2O ? Write an reaction formula with structural formula.

[Archer]

I don't see anything wrong with your answers, why do -OH groups make carbohydrates relatively more water soluble?

If the methanesulphonyl anion is a good leaving group, what kind of reaction do you think might take place?

What are the important properties of sodium ethoxide in this type of reaction?

[Archer]

Wikipedia suggests the complexation is an electrostatic interaction, this may be a good place to start for part 2

 http://www.sciencedirect.com/science/article/pii/S0040402006017315

[AmbitiousStudent]

I don't see anything wrong with your answers, why do -OH groups make carbohydrates relatively more water soluble?

Because of that OH-group is polar and water is polar and therefore will the negative oxygen part be attracted to the positive hydrogen part? Carbohydrates are not polar in the same extent since it is the OH-group that will make the carbohydrates polar.

Is that what you looking for?

[AmbitiousStudent]

Wikipedia suggests the complexation is an electrostatic interaction, this may be a good place to start for part 2

 http://www.sciencedirect.com/science/article/pii/S0040402006017315

Found this on wikipedia. " The hydrogen bond is often described as a strong electrostatic dipole-dipole interaction."http://en.wikipedia.org/wiki/Intermolecular_force#Hydrogen_bonding

Do you think this is correct and enough?

[spirochete]

Wikipedia suggests the complexation is an electrostatic interaction, this may be a good place to start for part 2

 http://www.sciencedirect.com/science/article/pii/S0040402006017315

Found this on wikipedia. " The hydrogen bond is often described as a strong electrostatic dipole-dipole interaction."http://en.wikipedia.org/wiki/Intermolecular_force#Hydrogen_bonding

Do you think this is correct and enough?

Many have suggested that hydrogen bonding is a combination of both simple electrostatics as well as more complicated orbital interactions. E.G. lone pair/sigma star donation.

The geometry of H bonding can be suggestive of how much the orbital interactions are really contributing on a case by case basis. If I recall, physical organic chemists have been noticing recently that geometry is usually not so important to make a hydrogen bond energetically stabilizing. This lack of a strict geometric requirement suggests that orbital interactions often play a relatively minor role.

PS sorry for the TMI!

[AmbitiousStudent]

Someone else who had some answers or some tips how I should continue?

[Archer]

Your answers are partially right but you are missing some key points which may lose you marks. This forum is designed to point you in the right direction, not pre-assess your assessments before you submit them.

 Did you read the paper that I posted a link to?

As for part 3 I can't help you anymore until you answer my previous questions.

[AmbitiousStudent]

Your answers are partially right but you are missing some key points which may lose you marks. This forum is designed to point you in the right direction, not pre-assess your assessments before you submit them.

 Did you read the paper that I posted a link to?

As for part 3 I can't help you anymore until you answer my previous questions.

Thanks for the article and I have read it but I do not really understand. I guess my knowledge within cheimstry is still to low to understand reaserch reports but I guess I the answer is within this paragraph

"complex in D2O displays on one hand two cross
peaks between the methylene protons of the crown and the
methylene protons of the Busulfan-butyl chain and on the
other hand, between the methyl protons of the Busulfan and
the methylene protons of the CD (C-6 connected to the urea
N–H atom). These results corroborate the above-observed
chemical-induced shifts and indicate that the Busulfan is
connected to the ureas N–H atoms at each extremity of the
crown, probably by H-bonds with its two ester oxygens,
that consequently forced the sulfomethyl protons to be located in close proximity to the CD C-6 methylene atom connected to the urea N–H nitrogens. Thus, concerning the
Busulfan central lipophilic butyl chain, it should lie across
the crown ether macrocycle in close proximity with the oxoethylene bridges. Considering the dimension of the bisureido crown ether existing cavity (which was estimated
between 5.1 to 5.4 A ˚), the distance between the two O3ester
oxygens (w5.2 A ˚), the conformation and the electron density
map of the guest,15
there is a high probability of N–H/O3
strong H-bond formation between N–H of ureas and ester
oxygen atoms in the [Busulfan/9] inclusion complex as illustrated in Figure 7.


Part 1.The report also talks about water soluble which should fit in

"A water-solubleC2-symmetric receptor including two bCDs connected by urea linkers to a chiral diaza-crown ether organising platform has been synthesised in eight steps and
characterised."

Which receptor are we talking about here?

Part 3: I think it will be a SN2 reaction due it is a good leaving group and a nucleophil will it go fast. Wikipedia also states that is a SN2. But I do not really understand how the  sodium ethoxide will affect it.

"Busulfan is an alkylsulfonate. It's an alkylating agent that forms DNA-DNA intrastrand crosslinks between theDNAbases guanine and adenine and between guanine and guanine.[3] This occurs through an SN2 reaction in which the relatively nucleophilic guanine N7 attacks the carbon adjacent to the mesylate (CH3SO3-) leaving group.DNA crosslinking prevents DNA replication. Because the intrastrand DNA crosslinks cannot be repaired by cellular machinery, the cell undergoes apoptosis."

[AmbitiousStudent]

As for part 3 I can't help you anymore until you answer my previous questions.

I think it have something to do with Zaitsev rule so I know which substitution product that will be the most common one but I do not really understand. Is this right or is it something completely else?

http://en.wikipedia.org/wiki/Zaitsev's_rule

[Archer]

As for part 3 I can't help you anymore until you answer my previous questions.

I think it have something to do with Zaitsev rule so I know which substitution product that will be the most common one but I do not really understand. Is this right or is it something completely else?

http://en.wikipedia.org/wiki/Zaitsev's_rule

You were on the right lines with S_N2

What is a nucleophile?

[orgopete]

Part 3: I think it will be a SN2 reaction due it is a good leaving group and a nucleophil will it go fast. Wikipedia also states that is a SN2. But I do not really understand how the  sodium ethoxide will affect it.

"Busulfan is an alkylsulfonate. It's an alkylating agent that forms DNA-DNA intrastrand crosslinks between theDNAbases guanine and adenine and between guanine and guanine.[3] This occurs through an SN2 reaction in which the relatively nucleophilic guanine N7 attacks the carbon adjacent to the mesylate (CH3SO3-) leaving group.DNA crosslinking prevents DNA replication. Because the intrastrand DNA crosslinks cannot be repaired by cellular machinery, the cell undergoes apoptosis."

This seems as though it is answering itself. The product does not contain ethoxide nor is it an elimination. The product is a cross link between DNA bases. If ethoxide acted as a base, now might the bis-mesylate react to cross-link DNA?