Hi!
Here is some information about the synthesis of the title compounds starting from Hydroquinone. It is not incredibly difficult, and a nice excersize that can be completed in about a week or so.
It goes as follows:
Hydroquinone --> 4-methoxyphenol --> 1-allyloxy-4-methoxybenzene --> 2-allyl-4-methoxyphenol --> 2-allyl-1,4-dimethoxybenzene --> 2-propyl-1,4-dimethoxybenzene --> 4-propyl-2,5-dimethoxybenzaldehyde --> 4-propyl-2,5-dimethoxy-beta-nitroethene --> 4-propyl-2,5-dimethoxyphenethylamine --> NBOMe-2C-P.

9 steps to the final compound, technically.

4-methoxyphenol is alkylated with allyl bromide, then the product is heated for Claisen rearrangement. The obtained 2-allyl-4-methoxyphenol is methylated with trimethyl phosphate to give 2-allyl-1,4-dimethoxybenzene (2,5-dimethoxyallylbenzene) then this is hydrogenated to give the 2-propyl-1,4-dimethoxybenzene. This is then formylated by the Sulfuric Duff to give the aldehyde, condensed and reduced to give 2C-P and finally reaction with 2-methoxybenzaldehyde/NaBH4 gives the final target.


4-methoxyphenol

This can be scaled to anything pretty much, and the larger the scale the larger the yield. Here is just one representative example.

Hydroquinone (50g, 454mmol) is dissolved in 200ml MeOH, p-benzoquinone (5g) is added then dropwise conc. H2SO4 (20ml). This is refluxed for 4 hours, the reaction mixture reduced to half it's volume in vacuo, poured into 200ml H2O and extracted 4x 50ml CH2Cl2.
The organic layer is washed 3x 100ml H2O then brine. The solvent is removed then the product vacuum distilled, short path.
Alternatively this can be distilled at atmospheric pressure, make sure to have even heating though. There seems to be no difference in the product obtained by either distillation method. This is simple as it gets.
There is obtained 34.6g (53%) white crystals in the receiving flask. Over time they will turn orange if not recrystallized but are fine for short term storage (few weeks) or immediate usage.

Good yield for this reaction.


1-allyloxy-4-methoxybenzene

There will be 2 examples given of the same reactions to show the difference made when using properly dry distilled DMF and freshly fused and powder K2CO3 against straight out of the bottle reagents. First is straight out of the bottles, as received from manufacturers (beside powdering of K2CO3).

In a 250ml RBF with stirbar, condenser and thermometer was added DMF (75ml) 4-methoxyphenol (12.4g, 100mmol) and powdered anhydrous K2CO3 (190mmol, 26.2g) and the mixture stirred for 5 minutes under argon.
There is added in one portion allyl bromide (18.1g, 150mmol) which results in gradual clouding of the reaction mixture. It is heated at 50-60C for 8hr then stirred overnight (12hr) at RT.
The mixture is diluted with 150ml H2O and extracted 3x 50ml toluene.
The organic layer is washed 100ml H2O, 2x 100ml 5% aq NaOH, then 2x 100ml H2O and brine.
The light straw colored extract is filtered through a cotton plug topped with Na2SO4 and the plug washed with toluene and the solvent evaporated in vacuo.
After holding the residue under vacuum to remove all traces of any toluene/DMF (this must be done to ensure success of the next step!!) there is obtained 14.2g of a light yellow oil, MW 164.2, 86.4% yield.


Now with better conditions:

In a 250ml RBF with stir bar, condenser and thermometer is added freshly distilled anhydrous DMF (75ml) and 4-methoxyphenol (11.4g, 91.8mmol) followed by freshly baked, finely powdered anhydrous K2CO3 (24.1g, 174.4mmol, 1.9eq) and the mixture stirred for 5 minutes under argon.
In one portion is added allyl bromide (16.6g, 1.5eq) and the mixture heated for 5hr at 50-60C then stirred overnight (~12hr).
The workup is performed as above with the exception of using CH2Cl2 as the solvent, and after removal of the solvents under vacuum there is obtained a light yellow oil in quantitative yield.

Nice simple SN2 reaction. The very good allyl electrophile always give good yield in SN2 reaction.



2-allyl-4-methoxyphenol

As mentioned above the benzene must be totally free of solvents, or the reaction will not occur as the temperature will not be high enough. THis is a take from PiHKAL.

The 14.2g 1-allyloxy-4-methoxybenzene obtained previously was heated to reflux with a flame over 10 minutes, and once refluxing was achieved it was held here for 5 minutes longer. Once cooled the red oil is basified by excess KOH solution (10-15%) and washed 2x 40ml CH2Cl2, then acidified with HCl and extracted 2x 50ml CH2Cl2.
The organic layer is washed 2x 100ml H2O then 50ml brine and dried on Na2SO4.
Removal of the solvent gave 9.8g amber oil, MW: 164.2, 69%.

Perhaps you should try longer reaction time to have better yield.

2-allyl-1,4-dimethoxybenzene

In a 250ml RBF containing 2-allyl-4-methoxyphenol (9.8g, 59.6mmol) was added stirbar and H2O (75ml) then this degassed with argon for 10 mins then KOH (4g, 1.2eq) was added and the mixture stirred under argon for 10 minutes.
Trimethyl phosphate (11.2g, 80.4mmol, 1.35eq) was added in one portion then the mixture stirred in a boiling waterbath for 1hr 30mins.
After cooling 50ml H2O was added and the mixture extracted with 2x 50ml CH2Cl2 then once 25ml.
The organic layer was washed with 100ml 5% aq NaOH, 100ml 5% HCl, once 100ml H2O then 50ml brine. After drying on Na2SO4 the solvent was removed to give 7.1g light amber oil, MW: 178.2, 66.7% yield.

I'm surprised you got decent yield with water as solvent. For every SN2 reaction for which I used water as solvent I got poor yield (using Me3PO4 or MeSO4 as alkylating agent) or worse than with aprotic polar solvent such as DMF, DMSO, NMP, ... Here you can use DMF/K2CO3 like in the above allylation or prepare before the K-salt of the phenolate and dissolve this latter in DMF or DMSO before treating it with the alkylating agent. Can be done at RT. No smell of Dimethylamine has been detected unlike dissolving KOH in DMF because DMF deconposes up on heating.

2-propyl-1,4-dimethoxybenzene

In a single neck 250ml RBF containing previously obtained allyl-benzene and stirbar was added 75ml 96% EtOH (undenatured) and the flask evacuated and filled with argon 3x then 0.5g 10% Pd/C was added and the flask evacuated again, then filled with H2 and stirred. The balloon delivering H2 needed to be refilled twice, likely due to small leaks.
It was stirred overnight then the next day 100mg of fresh catalyst was added and the mixture evacuated and filled with H2 and stirred under H2 balloon for 3 hours to ensure reduction.
The reaction mixture was then filtered through celite and the cake washed with 50ml EtOH.
After evaporation of the solvent in vacuo there was obtained 6.8g of a very pale yellow oil, MW: 180.2, 94.7% yield.

Very good protocol. High yield and no pressure is required. I'm very pleased. 


4-propyl-2,5-dimethoxybenzaldehyde

The above obtained oil (37.7mmol) was dissolved in AcOH (80ml) in a 250ml RBF. There was added hexamethylenetetramine (10.5g, 75.4mmol, 2eq) and after dissolution there is added dropwise with good stirring in an ice bath conc. H2SO4 (14.7g, 4eq). A white precipitate forms and the mixture becomes very thick.
After all has been added the mixture is heated to reflux for 2hr 30mins, then after cooling there is added 80ml 10% H2SO4 and 80ml EtOAc.
The mixture is stirred at RT for 24hr.

20ml of brine is added and the layers separated, and the aqueous layer extracted 4x 50ml EtOAc. The combined extracts are washed with 3x 150ml 10% NaCl then 100ml brine.
The solvent is evaporated to give 9g of an oil that contained some AcOH but was used in the next step without purification.

Here you used the Duff modified reaction ala Ullmann from sciencemadness. He claims having exceptionnal yield on para-alkylthio substrate but in fact the yield are barely over 50% base on my personal trials and these from hyperlab. I suggest another formylation such as standard Vilsmeyer if you have the reactant. The advantage of the method you used is its OTC label. Nevertheless its a good application of the modified Duff.

4-propyl-2,5-dimethoxy-beta-nitrostyrene

Perhaps the yield can be better if using isopropanol instead of MeOH..

The oil from above was dissolved in 20ml MeOH and 5ml AcOH was added.
There was added ethylenediamine (7 drops, ~10mol %) and nitromethane (3g, 2eq) and the mixture stirred then left wrapped in foil for 20hr at RT.
After breaking the crystals and leaving in freezer for 1hr, they are filtered and washed/triturated on the filter with 20ml ice cold MeOH.
There was obtained 3.53g of orange platelets, MW: 251.2 , 37.1% over 2 steps.

EDDA and EDA work excpetionally good on 2,5-dimethoxybenzaldehyde but if you try it on other substrates even 4-Me-DMB the yield will dramatically fall down to ~40-60 %. That's inevitable. Instead you should use 10mol% of aqueous MeNH2 in a minimal volume of MeOH and place in a rotavap at 60°C for 1h. Then cool it down by placing the flask in the fridge for the night. Next day , the crystals are filtered   out and washed with cold MeOH. Yield up to 95% have been reported for some substrate. Always better than 80%. MeNH2 can probably be  changed for EtNH2 but not NH4OH.

4-propyl-2,5-dimethoxyphenethylamine

In a 250ml RBF with stirbar and thermometer was added 50ml isopropanol and 21ml H2O. In one portion there was added NaBH4 (2.11g, 4eq, 56mmol) which resulted in light fizzing. After dissolution there is added potrtionwise above obtained nitrostyrene over about 15 minutes, the temperature climbs to about 50C and after addition the mixture is stirred for 30mins.
Then with cooling in an ice bath and at 0C the excess NaBH4 is killed by very cautious addition of 10ml AcOH, DROPWISE.
Then there is added Zn dust (9.1g, 10eq. 140mmol) and the flask removed from the ice bath, and over 30-40mins there is added dropwise 32% HCl (42ml, 3eq vs. Zn). The temperature reaches 40C, and then it is stirred for 2 hr longer at RT.

The mixture is filtered, cake washed with 30ml methanol and the IPA/MeOH removed under vacuum. The aqueous residue is basified with excess NaOH to dissolve salts, then extracted 4x 50ml toluene (CH2Cl2 usually gives emulsions, toluene is better). The organic layer is washed with 150ml 10% NaOH, then 2x 150ml H2O then 100ml brine.
The solvent is removed and the oil is decanted into a beaker, and the flask rinsed 3x with a few ml isopropanol. HCl is added dropwise until slit acidification then 30ml acetone is added which provokes crystallization. The beaker is chilled in the freezer for 2hr then the crystals are filtered and washed with 20ml ice cold acetone to give 1.61g of fluffy white crystals, 44% yield.

What a nice exemple of a 2-step reaction. For the reduction of the double bond you must not let the temperature rise above 20-30°C because of the polymerisation. A ice-bath is needed. A lot of experiments have been done such as HCOONH4/Zn, HCl/In wire, AcOH/Zn but none of these give yield better than the basic Zn/HCl like  you did. Perhaps HCOOH is a better acid ?


NBOMe-2C-P

1g 2C-P.HCl was added to a sep funnel containing 50ml 10% NaOH, and this swirled until all had converted to the freebase. This was extracted 3x 20ml CH2Cl2, washed 2x 50ml H2O then 40ml brine. After drying on Na2SO4 the solvent was evaporated to give the freebase, ~860mg (3.85mmol).
The base was dissolved in 25ml dry
MeOH and 2-methoxybenzaldehyde (530mg, 3.9mmol) was added, the mixture slowly became yellow and it was stirred overnight at RT.
The next day it was cooled to 0C then in one portion was added NaBH4 (190mg, ~5mmol) which resulted in loss of color and some fizzing. Ice bath removed and the mixture stirred for 12hr.
The solvents were removed in vacuo and the residue was dissolved in 80ml H2O and extracted 3x 25ml CH2Cl2. These were washed 2x 50ml H2O then brine, and after drying on Na2SO4 the solvent was evaporated to give an oil.
It was dissolved in a few ml IPA and acidified, then the solvent removed, 20ml IPA added and this also removed.
5ml acetone was added and overnight the oil had crystallized into fine needles, they were filtered and washed with cold acetone to give 660mg of glistening white needles. A second crop was obtained by leaving the filtrate In the freezer, it weighed 20mg.
Combined yield 680mg of the hydrochloride, 46.5% yield

Nice work here. I think you were a bit unlucky for the yield because it's quite bad for your perfect protocol.

It has not been bioassayed, due to lack of time to find an active dose. It is unknown what type of activity it may have.

Please feel free to add any information on synthesis of intermediates, different methods, etc.
This is simply one way to do it, there is always a way to optimize on several steps shown here.