Retrosynthetic analysis synthesis backwards

Most of the chemistry you have learned so far has concentrated on reactions (questions like what do you need to add to X to get Y ) or on products (questions like what will happen if X and Y react together ). Now we re looking at starting materials (questions like what X and Y do you need to react together to make Z ). We re looking at reactions in reverse, and we have a special symbol for a reverse reaction called a retrosynthetic arrow (the implies arrow from logic). 

A scheme with a retrosynthetic arrow Z —. - X + Y means Z could be made from X plus Y a retrosynthetic arrow 

This compound is used as an insect repellent, As it s an ester, we know that it can be made from alcohol plus acyl chloride, and we can represent this using a retrosynthetic arrow. 

The aromatic amide amelfolide is a cardiac antiarrhythmic agent. Because we see that it is an amide, we know that it can be made quite simply from p-nitrobenzoyl chloride and 2,6-dimethyl-aniline—again, we can represent this using a retrosynthetic arrow. Mentally breaking a molecule into its component parts like this is known as disconnection, and it s helpful to indicate the site of the disconnection with a wiggly line as we have here. 

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During this synthesis we have to make a new carbon-carbon bond. For our retrosynthetic analysis (going backwards) we cut this new bond with a squiggly line to make two pieces. As you will see on the next page, the challenge is to make these pieces and then make them bond them together. 

The retrosynthetic analysis of a target compound is a systematic approach in developing a synthesis plan starting with the target structure and working backward to available starting materials. 

When planning the synthesis of a compound using an organometallic reagent or indeed any synthesis the best approach is to reason backward from the product This method is called retrosynthetic analysis Retro synthetic analysis of 1 methylcyclohexanol suggests it can be prepared by the reaction of methylmagnesmm bromide and cyclohexanone... 

ANSWER We are using a Williamson Ether synthesis, so we will need to start with an alcohol and an alkyl halide to form the ether linkage. Working backwards (retrosynthetic analysis), we get the following ... 

Retrosynthetic analysis is a method for tackling synthesis problems, especially multistep synthesis problems. The application of this technique involves working the problem backwards, starting at the final product and ending up with the initial reactants. 

When applying retrosynthetic analysis to a multistep synthesis problem, you must work backwards. If you become lost, as a last resort you may want to look at the forward reactions. However, the forward process often goes off on a tangent or leads to a cul-de-sac. 

So the synthesis could be done in one step by making the anion of methyl acetate and reacting it with bromocyclohexane. The polarities of the reaction partners match nicely, but the problem is that alkylations of secondary bromides with enolates often give poor yields. The enolate is a strong base, which promotes elimination in the secondary bromide rather than giving the substitution product needed in the synthesis. Thus elimination from cyclohexyl bromide to cyclohexene would be a major process if the reaction were attempted. While the retrosynthetic step seems reasonable, the synthetic step has known difficulties. It is important to work backward in the retrosynthetic analysis and then check each forward step for validity. 

When you see a synthesis problem for the first time, you are not expected to immediately know the answer. I cannot stress this enough. It is so common for students to get overly anxious when they see synthesis problems that they cannot solve. Get used to it. This is the way it is supposed to be. Going back to our chess analogy, you don t need to make a move as soon as it is your turn. You are allowed to think about it first. In fact, you are supposed to think about it first. So, how do you begin thinking about a multistep synthesis problem w here you do not immediately see the solution The most powerful technique is called retrosynthetic analysis. This means that you analyze the problem backward. Let s see how this works w ith an example ... 

Remember that it helps to use retrosynthetic analysis in synthesis problems. This means working backward to simpler and simpler compounds until an available compound is reached. These problems offer an additional clue in that the starting material is specified. In such cases it is often useful to identify which carbons in the target come from the carbons of the starting material. It is usually advisable to change these carbons as little as possible. It is also useful to identify which carbon-carbon bonds must be formed in the synthesis and how any functional groups need to be modified. In some cases the entire path will be apparent after this examination. In others it will be neces-... 

The design of a synthesis for a complex molecule follows the same approach that was first introduced in Section 10.15, and amplified in Sections 11.14, 17.14, 18.11, and 20.11, that is, working backward from the target compound or retrosynthetic analysis. Recall that this process involves envisioning a reaction that can be used to prepare the target compound from a simpler compound. This simpler compound then becomes the target for the next step, and this process is continued until a commercially available compound is reached. 

Retrosynthetic analysis (Section 10.15) The process of designing a synthesis by working backward from the target compound. 

To plan a synthesis of more than one step, we use the process of retrosynthetic analysis— that is, working backwards from the desired product to determine the starting materials from which it is made (Section 10.18). To write a synthesis working backwards from the product to the starting material, an open arrow (= ) is used to indicate that the product is drawn on the left and the starting material on the right. 

To use the Heck reaction in synthesis, you must determine what alkene and what organic halide are needed to prepare a given compound. To work backwards, locate the double bond with the aryl, COOR, or CN substituent, and break the molecule into two components at the end of the C = C not bonded to one of these substituents. Sample Problem 26.3 illustrates this retrosynthetic analysis. 

Retrosynthetic Analysis. An approach to computer-assisted synthesis design that starts with the products of a reaction or sequence of reactions and works backwards toward the reactants. An example program that implements retrosynthetic analysis is the LHASA program of E. J. Corey s group. 

Designing a synthesis by working backward from product to reactant is not simply a technique taught to organic chemistry students. It is used so frequently by experienced synthetic chemists that it has been given a name—retrosynthetic analysis. 

Chemists use open arrows to indicate they are working backward. Typically, the reagents needed to carry out each step are not included until the reaction is written in the forward direction. For example, the route to the synthesis of the previous ketone can be arrived at by the following retrosynthetic analysis. 

The synthesis of a complicated molecule from simple starting materials is not always obvious. We have seen that it is often easier to work backward from the desired product to available starting materials—a process called retrosynthetic analysis (Section 6.11). In a retrosynthetic analysis, the chemist dissects a molecule into smaller and smaller pieces until readily available starting materials are obtained. 

Retrosynthetic analysis Planning a. synthesis by rea.soning backward from the desired product to identify important bonds. 

Synthetic planning starts with the product, which is fixed and unchangeable, and works backwards towards the starting materials. This process is called retrosynthesis, and the art of planning the synthesis of a target molecule is called retrosynthetic analysis. The aim of this chapter is to introduce you to the principles of retrosynthetic analysis once you have read and understood it you will be well on the way to designing your own organic syntheses. 

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