3.2.2.1     New Synthesis (Part II)

Confirming the stoichiometric equation with OK in Figure 3 leads back to the window of project where the input synthesis appears with its name (Figure 4, left hand).

Figure 4   Edit a new synthesis

Further syntheses, e.g. of the same product by other methodologies, similarly can be added by NEW or EXCHANGE of corresponding syntheses, which are input in other projects, already. But more concerning the topic EXCHANGE you can find in chapter 3.2.3. By clicking CLOSE you will return to the start window.

But normally, the synthesis input is processed following directly, to input and examine synthesis data and substance properties. By selecting the synthesis, you can operate with the buttons gray underlaid so far (Figure 4, right hand) and rename or delete the synthesis as usual. Via the button COMPARE several syntheses can be compared (chapter 3.7).Clicking the button OPEN, a new window appears, where you input all further data concerning the synthesis and the substance properties (Figure 6).

3.2.2.2     Command line for the editing of the synthesis

Figure 5   Edit synthesis and substance properties

The command line consists of FILE, EDIT, SYNTHESIS SEQUENCE, and ?.

Under FILE you can save the project or, as well as the synthesis, change it or terminate the program.

EDIT makes it possible, after the input of all data, to CALCULATE and visualize a graphic flip chart to the synthesis, among other things, mediating information on material input and output. This function corresponds to COMPARE in Figure 4, with the difference that only the synthesis opened at present is indicated. Further functions under EDIT are WEIGHTING (see chapter 3.3), LITERATURE (see chapter 3.4), SUBSTANCE LIST (see chapter 3.5), and MODE). The mode of the window in Figure 6 can be changed from SIMPLE into EXTENDED. However, the simple mode is completely sufficient to the full functionality of EATOS! Even it is sufficient to only input the substance quantities of all materials used (substrates, catalysts, solvents, and auxiliary materials) in [g] and the yield in [%]. However, specifications of volume always force the specification of the density. For a clearer reproduction of the substrate names in the detail views of the results‘ diagram (chapter 3.7), there is the possibility to indicate an abbreviation, e. g., DMSO instead of dimethyl sulfoxide. Adjusting the mode on EXTENDED, you can input into the investigation further knowledge concerning the synthesis. In this way, RECYCLABLE QUANTITIES and EMISSIONS known from a procedure can be integrated, and specifications on the degree of purity of the materials used can be refer to both, to an actually pollution not known in detail, and to substances in a material mixture, ADDITIONAL INGREDIENTS can be specified (see chapter 3.2.2.12). There exist further special input options, possible by the extended mode, for catalysts (chapter 3.2.2.6), product (chapter 3.2.2.9), coupled (chapter 3.2.2.10), and by-products (chapter 3.2.2.11).

Clicking SYNTHESIS SEQUENCE you can take over newly data changes in a selected substance of a synthesis in a synthesis sequence (also compare chapter 3.6.3) characterized by an imported product (also compare chapter 3.6.2) of another synthesis of the project opened, by REIMPORT, if this raw data file still exists. REIMPORT (RECURSIVE) means that all data of the synthesis opened will be updated. On the other hand, REIMPORT (RECURSIVE, FOR ALL SUBSTANCES) really causes an updating for all substances of the total synthesis sequence.

With ? HELP, a schematic overview of the MASS-BALANCE REGIONS and information on the program EATOS is callable.

3.2.2.3     Toolbar weighting, literature, substance list

Clicking WEIGHTING you can input material parameters, such as R-phrases and toxicological data for the synthesis‘ substances, for internally determining load factors which make possible a weighting of the material balance in view of environmentally relevant aspects for an estimation of the synthesis‘ danger potential. A description of the WEIGHTING is given in  chapter 3.3. Additionally, please refer to chapter 3.4 and chapter 3.5 for detailed explanations concerning the input of the literature and editing the substance list.

 

3.2.2.4      Comment field

The comment field on a register sheet of the window in Figure 6 serves for making notes concerning the respective substance in connection with the presently opened synthesis.

3.2.2.5     Substrates

The first view after opening (OPEN) a (new) synthesis according to Figure 4, is the register sheet SUBSTRATES (Figure 5). At the lower end, this register sheet is differentiated in the substrates input before, which are callable, respectively. The substrate marked with a blue point is the key-substrate, where yield and, if necessary, conversion base on. In case you determined the substrate wrongly when inputting the stoichiometric equation (see Figure 3) (--> check!), you can not correct this for the synthesis opened. Instead of this you must input the synthesis again!

In the simple mode, if meaningful, firstly you can determine an abbreviation which possibly later will allow a more clearly orientation in the detail view. The quantity indication can be made in different units and must be of one value > 0. Using the symbol , instead of [g], you can select [mol] or [ml], as well. In the last case, however, the indication of the density is necessary. According to literature, for the example of the synthesis of 4-methoxyacetophenone you input 1 mole ansiole, 1.05 mole acetyl chloride, and 1.2 mole AlCl3. With 500 g ice the necessary destruction of the keto-aluminum complex takes place. 3 moles can be ascribed to the substrates and the rest to the AUXILIARIY MATERIALS (chapter 3.2.2.8).

The button IMPORT makes it possible to overwrite the regarded substrate by a substance already saved in the substance list with a possibly more extensive data file with exception of the comment field, which inputs are preserved thereby. So that you do not need to search for the substrate in the total substance list, only substances with the same molecularly weight are displayed. Additionally, this button represents the central interface, which syntheses (under formation of a synthesis sequence) can be linked by with each other! For this purpose, you choose another synthesis in the same project, its product, now regarded as intermediate, enters the synthesis opened as substrate. A product already input in  the project in form of a synthesis can be imported as well when making out a subsequent synthesis using this product as synthesis, when inputting its stoichiometric equation (see Figure 3). Further information concerning the topic Import you will find in chapter 3.6.2.

By the button EXPORT you can export substances into the substance list, so that they are available for other applications with their total data file.

By the button RENAME you assign another name to a substance. By RESET you delete the register sheet-data input before.

In the extended mode (Figure 6), further information concerning the substrates can be brought in. If substrates are used in excess, and regained when processing or by the reaction guidance, you can indicate the RECYCLABLE QUANTITY. In case of available information concerning materials emitted during a procedure, you can input them under EMISSIONS. For the sake of the characterization, there exists the possibility to indicate the CAS-NUMBER of the substance (but the CAS-NUMBER has no further program-internal effects). Regarding the key substrate you can input the grade of the conversion, as far as known by gaschromatographical experiments. Internally, this indication automatically is ascribed to the other substrates, as well. Thereby and by the substrate excess the quantity of the non-converted substrates is determined internally. Generally, we recommend to follow preparative conversions gaschromatographically to be able to judge on the process of the synthesis. Additionally, you can consider the purity of the used substrates, which does not only exclusively mean the impurity only constituting little per cent points and being unknown in detail, but also additional ingredients, which can be indicated in detail in case of material mixtures. More information concerning the input of ADDITIONAL INGREDIENTS is described in chapter  3.2.2.12.

Figure 6   Extended mode at the example of the input of the substrates

 

3.2.2.6     Catalysts

With the name CATALYSTS not only do we mean real catalysts in this program. Furthermore, this register sheet is intended as well for initiators and activators which, generally, are used substoichiometric, but derived from the synthesis partially changed. In the example of the synthesis of 4-methoxyacetophenone – AlCl3 is regarded as substrate – we use no catalysts, so that the register-sheet CATALYSTS is explained by another example, that of the dibenzoyl peroxide induced hydrobromination of 10-undecylenic acid (A. Vogel, „Testbook of Practical Organic Chemistry“, Longman London & New 1978, ISBN 0-582-44250-8). In this radical addition reaction, under formation of 11-bromounedecanoic acid, dibenzoyl peroxide causes the chain initiation and converts itself into benzene and carbon dioxide (Formula Scheme 2).

Scheme 2         Dibenzoyl peroxide induced hydrobromination of 10-undecylenic acid

You input the catalysts in the corresponding register-sheet by firstly inputting the name (Figure 7).

Figure 7   Input of a catalyst

Afterwards, you input the further indications, analogously to the substrates – also in the unit [mol %]. Figure 8 already shows the extended mode.

Figure 8            Register sheet for catalysts in the extended mode

 

In addition to the input possibilities described in chapter 3.2.2.5 (SUBSTRATES), you can consider subsequent products resulting from the catalyst. The by-products resulting from the conversion of dibenzoyl peroxide are benzene and carbon dioxide and can be input under BY-PRODUCTS (CATALYST) SPECIFY... .

Figure 9            Specification of by-products of the catalyst I

After naming of a by-product (Figure 9), you put in the formed quantity and/or emissions (Figure 10).


Figure 10            Input of by-products resulting from the catalyst I

In case of the decompostition of dibenzoyl peroxide you can assume that about 64 % of the quantity converts into benzene. This amount approximately corresponds to the mass of two benzene rings in dibenzoyl peroxide. In this way, the remaining 36 % can be allocated to the emitting carbon dioxide. If you omit to input carbon dioxide, however, you also can indicate 100 % with the statement that the whole amount of dibenzyol peroxide converts into the substance benzene, at least. The mass difference is program-internally ascribed to the quantity of the unknown by-products from the catalyst. The input of the aspect that two molecules benzene per molecule dibenzoyl peroxide are formedis made under #BY-PRODUCT / #CATALYST, i.e., 2/1. The symbol ‚#‘ represents the term ‚number‘. Thereby, the internal calculation by indication of #BY-PRODUCT / #CATALYST refers to the molecular weights. Therefore, in this case you must input the formula of the catalyst as well as those of the by-product, what can be omitted otherwise. Subsequently, by NEW you correspondingly input the other by-product carbon dioxide with an amount of 36 % (Figure 11 and Figure 12 ).

Figure 11          Specifying by-products of the catalyst II

Of course, few materials used input under CATALYST convert into other substances. Such in the true sense catalytic working materials are input under CATALYST and no additional decomposition products are described. As examples we indicate heterogeneous catalysts such as Pd/C for hydration, or Nafion H, or K 10 for acid catalyzed reactions, or homogeneous catalysts like the Grubbs’s metathesis catalyst.

The toolbar IMPORT (see chapter 3.6.2) allows the involvement of a substance already present in the substance list as well as of a product saved in the project! In this way, synthesized catalysts inclusively the materials being necessary for  their production can be integrated into the regarded synthesis. However, generally it is not possible to indicate RECYCLABLE QUANTITIES. For this reason, you should input only the really needed quantity.


Figure 12          Input of by-products resulting from the catalyst II

 

3.2.2.7     Solvents

Similarly, as described in chapter SUBSTRATES 3.2.2.5, you input SOLVENTS in the corresponding register sheet. According to literature, the quantity of the solvent 1,2-dichloroethane used for the synthesis of 4-methoxyacetophenone amounts to 400 ml.

3.2.2.8     Auxiliary materials

Under AUXILIARY MATERIALS all further substances are indicated, which must be spent for the synthesis of the product. Among other things, there belong to reagents situated in the reaction vessel, which are not ascribed to the catalysts or solvents, as well as auxiliary materials which are needed for the isolation of the product as, e. g., washing water, extraction solvents, etc. Certainly, it is optional, e. g., to input all solvents in the register sheet SOLVENTS, also when they were used during the isolation. We differentiate between four miscellaneous mass balance regions: REACTION, ISOLATION, WASTE PRETREATMENT, and WASTE TREATMENT. If information is available, you can consider as well materials used for the pretreatment or treatment of the current waste material and assign it to the mass balance regions, correspondingly. In the command line under ? the mass balance regions are presented in an overview:

Figure 13          Mass balance regions REACTION, ISOLATION, WASTE PRE-TREATMENT, and WASTE TREATMENT

In other respects, as well concerning the auxiliary materials, input is made analogically to the substrates (chapter 3.2.2.5). In Figure 14 the register sheet AUXILIARY MATERIALS is filled out:


Figure 14          Input of auxiliary materials

In the case that own syntheses are not object of the study, but syntheses described in literature, often insufficient information on the auxiliaries is available. For this reason, for literature regulations the following assumptions were taken valid as standard:

·      extraction:                                                      300 ml solvent / liter aqueous medium

·      washing water:                                             300 ml water / liter solvent

·      washing saline solution:                              100 ml electrolyte solution / liter solvent

·      desiccant                                                      20 g desiccant / liter substance to be dried

For the example of the synthesis of 4-methodxyacetophenone, you gain the following assumptions and reasonably list them in the respective register sheet under COMMENT: 500 g ice ® 150 ml 1,2-dichloroethane (extraction), thus, totally 550 ml ® a) 165 ml washing water; b) 55 ml sodium hydroxid solution (2 %); c) 11 g potassium carbonate.

 

3.2.2.9     Product

You input the quantity of the product obtained at the synthesis in the corresponding register sheet in [g], [m], [ml], or [%] (referring to the key substrate), i.e., for the example of the synthesis of 4-methoxyacetophenone 60%. The input in [ml] requires the indication of the density. Possibly, graschromatographical studies of the raw product showed a higher yield than obtained after the isolation. For the input of this information, you must tick off the toolbar YIELD (GASCHROM.) KNOWN under YIELD (GASCHROMATOGRAPHICALLY), and then, additionally, input the value in the input-line underneath, so that the yield obtained gaschromatographically makes possible a determination of the yield loss by the work-up procedure. Naturally, the gaschromatographical yield must become a higher value than the isolated yield and a lower than the CONVERSION input under SUBSTRATES (see chapter 3.2.2.5).

Beyond it, there exists the possibility to consider the formation of possible undesired diastereoisomers or enantiomers by firstly selecting under ISOMERIC RATIO between ENANTIOMERIC RATIO, ENANTIOMERIC EXCESS and DIASTEREOMERIC RATIO.. In the input-line underneath you input the corresponding value, e.g., 90 : 10 for the indication of a relation of isomers and 80 for an enantiomeric excess. The made product always is the default-indication of the NAME OF ISOMER and must be changed, correspondingly, i.e., e.g., you must precede with „S-“ or „D-„. The corresponding quantity from the product will be subtracted program internally and assigned to the isomer.

The functionality of the remaining toolbars corresponds to the substrates described in chapter 3.2.2.5.

Figure 15                      Input of the product

 

3.2.2.10     Coupled Products

According to the stoichiometric equation of the synthesis inevitably formed coupled products are listened in the respective register sheet. Here, no specifications are necessary, because the quantities formed in the synthesis dependent on the stoichiometric equation and the yield are calculated internally. Indeed, in some cases coupled products are regarded as value product beside the product. This is the case, e.g., if they are used as raw materials in other syntheses or if they are used already as a raw material in the synthesis‘ run regarded, or if they are utilizable anew in the circulation system after recovery. By input of the USEFUL QUANTITY of the utilizable coupled products in the corresponding input-line, these coupled products can be characterized correspondingly and the quantities can be indicated later in the graphic diagram . Thereby, the percentage indication refers to the conversion of the key product and, therefore, it may not exceed the yield.

For the description of the remaining toolbars see chapter Substrates 3.2.2.5.

Figure 16          Register sheet coupled products

 

3.2.2.11     By-products

The yield-reducing conversion of substrates to undesirable by-products takes places, if besides the desired synthesis there are running side reactions, which are competitive to it, or if subsequent reactions occur . As an example we mention the Friedel-Crafts-Alkylation where, by further alkylations, a reduction of the yield of the monoalkylated product is the consequence. Another example, to pick up the synthesis of 4-methoxyacetophenone used until now, is the formation of the by-product 2-methoxyacetophenone from the acylation of anisole at the ortho-position .

Program-internally, the quantity of these by-products defined by stoichiometric equation and yield is determined, so that you must not make any indications in this register sheet. But if there are known single by-products as well as the quantities of their formation, you should indicate them, to be able to consider their substance specific characteristics in the terms of the synthesis. Utilizable by-products can be marked with a cross under BY-PRODUCT USEFUL, so that they can be identified in the graphical diagram as value product. For demonstration, in Figure 17 we input a virtual by-product 1, which quantity has to be input.

Figure 17          Register sheet by-products

 

 3.2.2.12     Additional ingredients

For all entered substances of the synthesis you can indicate a degree of purity. With the purity which can rely on a real impurity not known in detail as well as on further substances in a substance mixture, you can specify ADDITIONAL INGREDIENTS (Figure 18) – in the example synthesis those of an auxiliary (2% sodium hydroxide solution) – and allocate them under KIND OF SUBSTANCE to the categories IMPURITY, AQUEOUS MEDIUM or MISCELLANEOUS (Figure 19).

Figure 18          Input of an additional ingredient to an ‚impure‘ substance I

 


Figure 19          Input of an additional ingredient to an ‚impure‘ substance II

For these assignments in the graphic presentation of the results there exist own, appropriately selectable categories. Under these categories, exactly those substance quantities are specified which got the corresponding assignment as further contents material. Under ‚SEWAGE/WATER‘, e.g., ingredients appear which assignment is made under KIND OF SUBSTANCE to AQUEOUS MEDIUM. The opposite consequence is as well that only those materials can appear which were input under AUXILIARY MATERIALS. Thus, the SOLVENT water or the AUXILIARY MATERIAL water is not listed under ‚ SEWAGE/WATER‘ but under the category solvents or auxiliary material, respectively. Only an ADDITIONAL INGREDIENTS can be categorized in that way. But in the matter of principle – by a short way round – it is possible to allocate water used as solvent or auxiliary to the category ‚SEWAGE/WATER ‘. For this, you must input, e.g., the solvent water with a very low purity, e.g., 0.001 %, and redefine water under ADDITIONAL INGREDIENTS  with the remaining 99.999 %.

By the option ADDITIONAL INGREDIENTS any material mixtures can be input. In the following, we specify to examples for the input of material mixtures:

A commercially achievable 48% acetous hydrogen bromide solution has a pureness of 48% and additionally contains of the ingredient acetic acid, which you must assign to the category MISCELLANEOUS under KIND OF SUBSTANCE and is available in an amount of 52%.

A saturated aqueous sodium pyrosulfite solution (solubility of Na2S2O5 at 20°C: 54 g / 100 g water; see Handbook of Chemistry and Physics, David R. Lide, 73rd Edition 1992 – 1993, ISBN 0-8493-0473-3, p. 4 – 101) consists of a salt share of (54 / 154 =) 35,06%, what is the reason why the proportion of water amounts to 54,94%, which is assigned to the category AQUEOUS MEDIUM under KIND OF SUBSTANCE.

 

Back to Main Menu Next Chapter