Disconnected

Disconnected structures in the molecule Individual parts of the compound are separated by a period. The period indicates that there is no connection between atoms or parts of a molecule. The arrangement of the parts is arbitrary. 

Conversely, a disconnected graph (null graph) coniains... 

To recognize the different levels of representation of biochemical reactions To understand metabolic reaction networks To know the principles of retrosynthetic analysis To understand the disconnection approach To become familiar with synthesis design systems... 

The specific transformations that disconnect the strategic bonds in the desired fashion are performed. 

Figure lO.J-31. Disconnection of the strategic bond yields (charged) synthons. The synthons are then transformed into neutral, stable reactants. 

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

The disconnection strategy Carbon-Heteroatom Bonds gives only one strategic bond, which is rated with a value of 100. 

Figure 10.3-50. Disconnection of a strategic bond and generation of a synthesis precursor...

The strategic bond is disconnected by just clicking with the mouse on it. A suitable synthesis precursor is then generated automatically by WODCA by adding appropriate atoms or groups to the open valences. 

The disconnection of the strategic bond rated 100 corresponds to an cstcrifiea-tion in the synthesis direction (Figure 10.3-51). Compound 1 is converted to 2 as a suitable synthesis precursor and, indeed, in the synthesis direction 2 can easily be converted to 1. 

In order to continue the design of a synthesis, 2 is now analysed further by the disconnection strategy for aliphatic bonds. WODCA detects two strategic bonds which are rated 100 and 67, respectively. The disconnection of the bond with the highest rating forms two precursor compounds, 3 and 4 (Figure 10,3-52),... 

Figure 10.3-54 illustrates how the reaction center is derived from the disconnection of the strategic bond and which additional bond spheres are considered in the definition of the reaction substructure search queiy. 

The disconnection approach has basically changed the view on planning a synthesis. 

S. Warren, Organic Synthesis - The Disconnection Approach, Wiley, Chichester, 1982. 

Students should carry out the purification by steam distillation of (a) crude nitrobenzene or chlorobenzene, or of (b) crude naphthalene, o-nitrophenol (p. 170) or />-tolunitrile (p. 194) as examples of solid compounds which may also be purified in this way. When the distillation is complete, disconnect the tubing (Fig. 15) between C and D before removing the flame from under D, otherwise the contents of C will be sucked back into D as the latter cools. 

Place 5 mi. of ethyl acetate in a 100 ml. round-bottomed flask, and add about 50 ml. of 10% sodium hydroxide solution, together with some fragments of ungiazed porcelain. Fit the flask with a reflux water-condenser, and boil the mixture gently over a wire gauze for 30 minutes. Now disconnect the condenser, and fit it by means of a bent delivery-tube (or knee-tube ) to the flask for direct distillation (Fig. 59, or Fig. 23(0), p. 45). Reheat the liquid, and collect the first 10 ml. of distillate, which will consist of a dilute aqueous solution of ethanol. Confirm the presence of ethanol by the iodoform test Test 3, p. 336). 

Disconnect the column, and remove the flask from the oil-bath. Add 25 ml. of dilute hydrochloric acid to the flask, shake the contents vigorously, and chill in ice-water, when crystals of benzhydrol will separate. (Occasionally the hydrol will separate initially as an oil, which ciystallises on vigorous stirring.)... 

Now disconnect the condenser and re-attach it to the flask by a knee-tube for distillation (Fig. 59, p. 100), unless the apparatus in Fig. 38 has been used. Distil off about 5 ml. of the liquid. 

If preferred, the following alternative procedure may be adopted. The absolute alcohol is placed in a 1 5 or 2 litre three-necked flask equipped with a double surface reflux condenser and a mercury-sealed mechanical stirrqr the third neck is closed with a dry stopper. The sodium is introduced and, when it has reacted completely, the ester is added and the mixture is gently refluxed for 2 hours. The reflux condenser is then rapidly disconnected and arranged for downward distillation with the aid of a short still head or knee tube. The other experimental details are as above except that the mixture is stirred during the distillation bumping is thus reduced to a minimum. 

Owing to the corrosive action of bromine upon corks j-jg 7, l. and rubber stoppers, ground glass joints are recommended in this preparation. The apparatus, depicted in Fig. Ill, 37, 1, is particularly convenient for the preparation of bromides from alcohols. A double surface condenser is fitted into D and a round-bottomed flask is fitted on to the ground glass joint at C R is a three-way stopcock f which permits the removal of the contents of A without disconnecting the apparatus. For preparations of moderate size, A has a capacity of 60 or 100 ml. and a 250 or 500 ml. flask is attached at C. 

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